2012
Dumas, Andrew; Dierksen, Gregory A; Gurol, M Edip; Halpin, Amy; Martinez-Ramirez, Sergi; Schwab, Kristin; Rosand, Jonathan; Viswanathan, Anand; Salat, David H; Polimeni, Jonathan R; Greenberg, Steven M
Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy Journal Article
In: Ann Neurol, vol. 72, no. 1, pp. 76–81, 2012, ISSN: 1531-8249.
@article{pmid22829269,
title = {Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy},
author = {Andrew Dumas and Gregory A Dierksen and M Edip Gurol and Amy Halpin and Sergi Martinez-Ramirez and Kristin Schwab and Jonathan Rosand and Anand Viswanathan and David H Salat and Jonathan R Polimeni and Steven M Greenberg},
doi = {10.1002/ana.23566},
issn = {1531-8249},
year = {2012},
date = {2012-07-01},
journal = {Ann Neurol},
volume = {72},
number = {1},
pages = {76--81},
abstract = {OBJECTIVE: In addition to its role in hemorrhagic stroke, advanced cerebral amyloid angiopathy (CAA) is also associated with ischemic lesions and vascular cognitive impairment. We used functional magnetic resonance imaging (MRI) techniques to identify CAA-associated vascular dysfunction.nnMETHODS: Functional MRI was performed on 25 nondemented subjects with probable CAA (mean ± standard deviation age, 70.2 ± 7.8 years) and 12 healthy elderly controls (age, 75.3 ± 6.2 years). Parameters measured were reactivity to visual stimulation (quantified as blood oxygen level-dependent [BOLD] response amplitude, time to peak response, and time to return to baseline after stimulus cessation) and resting absolute cerebral blood flow in the visually activated region (measured by arterial spin labeling).nnRESULTS: CAA subjects demonstrated reduced response amplitude (percentage change in BOLD signal, 0.65 ± 0.28 vs 0.89 ± 0.14; p < 0.01), prolonged time to peak (11.1 ± 5.1 vs 6.4 ± 1.8 seconds; p < 0.001), and prolonged time to baseline (16.5 ± 6.7 vs 11.6 ± 3.1 seconds; p < 0.001) relative to controls. These differences were independent of age, sex, and hypertension in multivariable analysis and were also present in secondary analyses excluding nonresponsive voxels or voxels containing chronic blood products. Within the CAA group, longer time to peak correlated with overall volume of white matter T2 hyperintensity (Pearson correlation, 0.53; p = 0.007). Absolute resting blood flow in visual cortex, in contrast, was essentially identical between the groups (44.0 ± 12.6 vs 45.0 ± 10.0 ml/100 g/min, p = 0.8).nnINTERPRETATION: Functional MRI identifies robust differences in both amplitude and timing of the response to visual stimulation in advanced CAA. These findings point to potentially powerful approaches for identifying the mechanistic links between vascular amyloid deposits, vascular dysfunction, and CAA-related brain injury.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: In addition to its role in hemorrhagic stroke, advanced cerebral amyloid angiopathy (CAA) is also associated with ischemic lesions and vascular cognitive impairment. We used functional magnetic resonance imaging (MRI) techniques to identify CAA-associated vascular dysfunction.nnMETHODS: Functional MRI was performed on 25 nondemented subjects with probable CAA (mean ± standard deviation age, 70.2 ± 7.8 years) and 12 healthy elderly controls (age, 75.3 ± 6.2 years). Parameters measured were reactivity to visual stimulation (quantified as blood oxygen level-dependent [BOLD] response amplitude, time to peak response, and time to return to baseline after stimulus cessation) and resting absolute cerebral blood flow in the visually activated region (measured by arterial spin labeling).nnRESULTS: CAA subjects demonstrated reduced response amplitude (percentage change in BOLD signal, 0.65 ± 0.28 vs 0.89 ± 0.14; p < 0.01), prolonged time to peak (11.1 ± 5.1 vs 6.4 ± 1.8 seconds; p < 0.001), and prolonged time to baseline (16.5 ± 6.7 vs 11.6 ± 3.1 seconds; p < 0.001) relative to controls. These differences were independent of age, sex, and hypertension in multivariable analysis and were also present in secondary analyses excluding nonresponsive voxels or voxels containing chronic blood products. Within the CAA group, longer time to peak correlated with overall volume of white matter T2 hyperintensity (Pearson correlation, 0.53; p = 0.007). Absolute resting blood flow in visual cortex, in contrast, was essentially identical between the groups (44.0 ± 12.6 vs 45.0 ± 10.0 ml/100 g/min, p = 0.8).nnINTERPRETATION: Functional MRI identifies robust differences in both amplitude and timing of the response to visual stimulation in advanced CAA. These findings point to potentially powerful approaches for identifying the mechanistic links between vascular amyloid deposits, vascular dysfunction, and CAA-related brain injury.
Dobromyslin, Vitaly I; Salat, David H; Fortier, Catherine B; Leritz, Elizabeth C; Beckmann, Christian F; Milberg, William P; McGlinchey, Regina E
Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis Journal Article
In: Neuroimage, vol. 60, no. 4, pp. 2073–2085, 2012, ISSN: 1095-9572.
@article{pmid22342804,
title = {Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis},
author = {Vitaly I Dobromyslin and David H Salat and Catherine B Fortier and Elizabeth C Leritz and Christian F Beckmann and William P Milberg and Regina E McGlinchey},
doi = {10.1016/j.neuroimage.2012.01.139},
issn = {1095-9572},
year = {2012},
date = {2012-05-01},
journal = {Neuroimage},
volume = {60},
number = {4},
pages = {2073--2085},
abstract = {Cerebellar functional circuitry has been examined in several prior studies using resting fMRI data and seed-based procedures, as well as whole-brain independent component analysis (ICA). Here, we hypothesized that ICA applied to functional data from the cerebellum exclusively would provide increased sensitivity for detecting cerebellar networks compared to previous approaches. Consistency of group-level networks was assessed in two age- and sex-matched groups of twenty-five subjects each. Cerebellum-only ICA was compared to the traditional whole-brain ICA procedure to examine the potential gain in sensitivity of the novel method. In addition to replicating a number of previously identified cerebellar networks, the current approach revealed at least one network component that was not apparent with the application of whole brain ICA. These results demonstrate the gain in sensitivity attained through specifying the cerebellum as a target structure with regard to the identification of robust and reliable networks. The use of similar procedures could be important in further expanding on previously defined patterns of cerebellar functional anatomy, as well as provide information about unique networks that have not been explored in prior work. Such information may prove crucial for understanding the cognitive and behavioral importance of the cerebellum in health and disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cerebellar functional circuitry has been examined in several prior studies using resting fMRI data and seed-based procedures, as well as whole-brain independent component analysis (ICA). Here, we hypothesized that ICA applied to functional data from the cerebellum exclusively would provide increased sensitivity for detecting cerebellar networks compared to previous approaches. Consistency of group-level networks was assessed in two age- and sex-matched groups of twenty-five subjects each. Cerebellum-only ICA was compared to the traditional whole-brain ICA procedure to examine the potential gain in sensitivity of the novel method. In addition to replicating a number of previously identified cerebellar networks, the current approach revealed at least one network component that was not apparent with the application of whole brain ICA. These results demonstrate the gain in sensitivity attained through specifying the cerebellum as a target structure with regard to the identification of robust and reliable networks. The use of similar procedures could be important in further expanding on previously defined patterns of cerebellar functional anatomy, as well as provide information about unique networks that have not been explored in prior work. Such information may prove crucial for understanding the cognitive and behavioral importance of the cerebellum in health and disease.
Chen, J Jean; Salat, David H; Rosas, H Diana
Complex relationships between cerebral blood flow and brain atrophy in early Huntington's disease Journal Article
In: Neuroimage, vol. 59, no. 2, pp. 1043–1051, 2012, ISSN: 1095-9572.
@article{pmid21945790,
title = {Complex relationships between cerebral blood flow and brain atrophy in early Huntington's disease},
author = {J Jean Chen and David H Salat and H Diana Rosas},
doi = {10.1016/j.neuroimage.2011.08.112},
issn = {1095-9572},
year = {2012},
date = {2012-01-01},
journal = {Neuroimage},
volume = {59},
number = {2},
pages = {1043--1051},
abstract = {Alterations in cerebral blood flow (CBF) may play an important role in the pathophysiology of neurodegenerative disorders such as Huntington's disease (HD). While a few reports have suggested reductions in CBF in HD, little is known about their extent and whether, or how, they might be related to atrophy and to clinical symptoms. We used pulsed arterial-spin labeling MRI in conjunction with high-resolution anatomical MRI to non-invasively measure regional CBF in 17 early stage HD subjects and 41 age- and gender-matched healthy controls. We found profound yet heterogeneous CBF reductions in the cortex, extending to the sensorimotor, paracentral, inferior temporal and lateral occipital regions, with sparing of the neighboring postcentral gyrus, insula and medial occipital areas. As expected, CBF in subcortical regions was also profoundly reduced, and to a similar degree. Unexpectedly, however, the association between CBF reductions and regional atrophy was complex, the two being directly associated in certain areas but not with others. In contrast, CBF was associated with performance on the Stroop, suggesting a potentially important role for alterations in CBF in cognitive deficits in HD. The work described here may have broad-reaching implications for our understanding of HD pathogenesis, progression and emerging therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alterations in cerebral blood flow (CBF) may play an important role in the pathophysiology of neurodegenerative disorders such as Huntington's disease (HD). While a few reports have suggested reductions in CBF in HD, little is known about their extent and whether, or how, they might be related to atrophy and to clinical symptoms. We used pulsed arterial-spin labeling MRI in conjunction with high-resolution anatomical MRI to non-invasively measure regional CBF in 17 early stage HD subjects and 41 age- and gender-matched healthy controls. We found profound yet heterogeneous CBF reductions in the cortex, extending to the sensorimotor, paracentral, inferior temporal and lateral occipital regions, with sparing of the neighboring postcentral gyrus, insula and medial occipital areas. As expected, CBF in subcortical regions was also profoundly reduced, and to a similar degree. Unexpectedly, however, the association between CBF reductions and regional atrophy was complex, the two being directly associated in certain areas but not with others. In contrast, CBF was associated with performance on the Stroop, suggesting a potentially important role for alterations in CBF in cognitive deficits in HD. The work described here may have broad-reaching implications for our understanding of HD pathogenesis, progression and emerging therapies.
Salat, David H; Williams, Victoria J; Leritz, Elizabeth C; Schnyer, David M; Rudolph, James L; Lipsitz, Lewis A; McGlinchey, Regina E; Milberg, William P
Inter-individual variation in blood pressure is associated with regional white matter integrity in generally healthy older adults Journal Article
In: Neuroimage, vol. 59, no. 1, pp. 181–192, 2012, ISSN: 1095-9572.
@article{pmid21820060,
title = {Inter-individual variation in blood pressure is associated with regional white matter integrity in generally healthy older adults},
author = {David H Salat and Victoria J Williams and Elizabeth C Leritz and David M Schnyer and James L Rudolph and Lewis A Lipsitz and Regina E McGlinchey and William P Milberg},
doi = {10.1016/j.neuroimage.2011.07.033},
issn = {1095-9572},
year = {2012},
date = {2012-01-01},
journal = {Neuroimage},
volume = {59},
number = {1},
pages = {181--192},
abstract = {Prior studies have documented a range of brain changes that occur as a result of healthy aging as well as neural alterations due to profound dysregulation in vascular health such as extreme hypertension, cerebrovascular disease and stroke. In contrast, little information exists about the more transitionary state between the normal and abnormal physiology that contributes to vascular disease and cognitive decline. Specifically, little information exists with regard to the influence of systemic vascular physiology on brain tissue structure in older individuals with low risk for cerebrovascular disease and with no evidence of cognitive impairment. We examined the association between resting blood pressure and diffusion tensor imaging (DTI) indices of white matter microstructure in 128 healthy older adults (43-87 years) spanning the normotensive to moderate-severe hypertensive range. Mean arterial blood pressure (MABP) was related to diffusion measures in several regions of the brain with greatest associations in the anterior corpus callosum and lateral frontal, precentral, superior frontal, lateral parietal and precuneus white matter. Associations between white matter integrity and blood pressure remained when controlling for age, when controlling for white matter lesions, and when limiting the analyses to only normotensive, pharmacologically controlled and pre-hypertensive individuals. Of the diffusion measures examined, associations were strongest between MABP and radial diffusivity which may indicate that blood pressure has an influence on myelin structure. Associations between MABP and white matter integrity followed spatial patterns resembling those often attributed to the effects of chronological age, suggesting that systemic cerebrovascular health may play a role in neural tissue degeneration classically ascribed to aging. These results demonstrate the importance of the consideration of vascular physiology in studies of cognitive and neural aging, and that this significance extends to even the normotensive and medically controlled population. These data additionally suggest that optimal management of blood pressure may require consideration of the more subtle influence of vascular health on neural health in addition to the primary goal of prevention of a major cerebrovascular event.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Prior studies have documented a range of brain changes that occur as a result of healthy aging as well as neural alterations due to profound dysregulation in vascular health such as extreme hypertension, cerebrovascular disease and stroke. In contrast, little information exists about the more transitionary state between the normal and abnormal physiology that contributes to vascular disease and cognitive decline. Specifically, little information exists with regard to the influence of systemic vascular physiology on brain tissue structure in older individuals with low risk for cerebrovascular disease and with no evidence of cognitive impairment. We examined the association between resting blood pressure and diffusion tensor imaging (DTI) indices of white matter microstructure in 128 healthy older adults (43-87 years) spanning the normotensive to moderate-severe hypertensive range. Mean arterial blood pressure (MABP) was related to diffusion measures in several regions of the brain with greatest associations in the anterior corpus callosum and lateral frontal, precentral, superior frontal, lateral parietal and precuneus white matter. Associations between white matter integrity and blood pressure remained when controlling for age, when controlling for white matter lesions, and when limiting the analyses to only normotensive, pharmacologically controlled and pre-hypertensive individuals. Of the diffusion measures examined, associations were strongest between MABP and radial diffusivity which may indicate that blood pressure has an influence on myelin structure. Associations between MABP and white matter integrity followed spatial patterns resembling those often attributed to the effects of chronological age, suggesting that systemic cerebrovascular health may play a role in neural tissue degeneration classically ascribed to aging. These results demonstrate the importance of the consideration of vascular physiology in studies of cognitive and neural aging, and that this significance extends to even the normotensive and medically controlled population. These data additionally suggest that optimal management of blood pressure may require consideration of the more subtle influence of vascular health on neural health in addition to the primary goal of prevention of a major cerebrovascular event.
2011
Fortier, Catherine B; Leritz, Elizabeth C; Salat, David H; Venne, Jonathan R; Maksimovskiy, Arkadiy L; Williams, Victoria; Milberg, William P; McGlinchey, Regina E
Reduced cortical thickness in abstinent alcoholics and association with alcoholic behavior Journal Article
In: Alcohol Clin Exp Res, vol. 35, no. 12, pp. 2193–2201, 2011, ISSN: 1530-0277.
@article{pmid21919920,
title = {Reduced cortical thickness in abstinent alcoholics and association with alcoholic behavior},
author = {Catherine B Fortier and Elizabeth C Leritz and David H Salat and Jonathan R Venne and Arkadiy L Maksimovskiy and Victoria Williams and William P Milberg and Regina E McGlinchey},
doi = {10.1111/j.1530-0277.2011.01576.x},
issn = {1530-0277},
year = {2011},
date = {2011-12-01},
journal = {Alcohol Clin Exp Res},
volume = {35},
number = {12},
pages = {2193--2201},
abstract = {BACKGROUND: Chronic misuse of alcohol results in widespread damage to the brain. Prior morphometric studies have examined cortical atrophy in individuals with alcoholism; however, no previous studies have examined alcohol-associated atrophy using cortical thickness measurements to obtain regional mapping of tissue loss across the full cortical surface.nnMETHODS: We compared cortical thickness measures from 31 abstinent individuals with a history of prior alcohol abuse to 34 healthy nonalcoholic control participants (total sample size = 65). Cortical surface models were created from high-resolution T1-weighted images, and cortical thickness was then estimated as the distance between the gray matter/white matter boundary and the outer cortical surface.nnRESULTS: Abstinent alcoholics showed reduced whole-brain thickness as compared to nonalcoholic participants. Decreases in thickness were found bilaterally in (i) superior frontal, (ii) precentral, (iii) postcentral, (iv) middle frontal, (v) middle/superior temporal, (vi) middle temporal, and (vii) lateral occipital cortical regions. Decreased cortical thickness in the alcoholic group was associated with severity of alcohol abuse.nnCONCLUSIONS: These findings demonstrate widespread reduction in cortical thickness as a consequence of chronic alcoholism, with most severe reductions in frontal and temporal brain regions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Chronic misuse of alcohol results in widespread damage to the brain. Prior morphometric studies have examined cortical atrophy in individuals with alcoholism; however, no previous studies have examined alcohol-associated atrophy using cortical thickness measurements to obtain regional mapping of tissue loss across the full cortical surface.nnMETHODS: We compared cortical thickness measures from 31 abstinent individuals with a history of prior alcohol abuse to 34 healthy nonalcoholic control participants (total sample size = 65). Cortical surface models were created from high-resolution T1-weighted images, and cortical thickness was then estimated as the distance between the gray matter/white matter boundary and the outer cortical surface.nnRESULTS: Abstinent alcoholics showed reduced whole-brain thickness as compared to nonalcoholic participants. Decreases in thickness were found bilaterally in (i) superior frontal, (ii) precentral, (iii) postcentral, (iv) middle frontal, (v) middle/superior temporal, (vi) middle temporal, and (vii) lateral occipital cortical regions. Decreased cortical thickness in the alcoholic group was associated with severity of alcohol abuse.nnCONCLUSIONS: These findings demonstrate widespread reduction in cortical thickness as a consequence of chronic alcoholism, with most severe reductions in frontal and temporal brain regions.
Rosas, H Diana; Reuter, Martin; Doros, Gheorghe; Lee, Stephanie Y; Triggs, Tyler; Malarick, Keith; Fischl, Bruce; Salat, David H; Hersch, Steven M
A tale of two factors: what determines the rate of progression in Huntington's disease? A longitudinal MRI study Journal Article
In: Mov Disord, vol. 26, no. 9, pp. 1691–1697, 2011, ISSN: 1531-8257.
@article{pmid21611979,
title = {A tale of two factors: what determines the rate of progression in Huntington's disease? A longitudinal MRI study},
author = {H Diana Rosas and Martin Reuter and Gheorghe Doros and Stephanie Y Lee and Tyler Triggs and Keith Malarick and Bruce Fischl and David H Salat and Steven M Hersch},
doi = {10.1002/mds.23762},
issn = {1531-8257},
year = {2011},
date = {2011-08-01},
journal = {Mov Disord},
volume = {26},
number = {9},
pages = {1691--1697},
abstract = {Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Huntington's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Huntington's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease.
Walhovd, Kristine B; Westlye, Lars T; Amlien, Inge; Espeseth, Thomas; Reinvang, Ivar; Raz, Naftali; Agartz, Ingrid; Salat, David H; Greve, Doug N; Fischl, Bruce; Dale, Anders M; Fjell, Anders M
Consistent neuroanatomical age-related volume differences across multiple samples Journal Article
In: Neurobiol Aging, vol. 32, no. 5, pp. 916–932, 2011, ISSN: 1558-1497.
@article{pmid19570593,
title = {Consistent neuroanatomical age-related volume differences across multiple samples},
author = {Kristine B Walhovd and Lars T Westlye and Inge Amlien and Thomas Espeseth and Ivar Reinvang and Naftali Raz and Ingrid Agartz and David H Salat and Doug N Greve and Bruce Fischl and Anders M Dale and Anders M Fjell},
doi = {10.1016/j.neurobiolaging.2009.05.013},
issn = {1558-1497},
year = {2011},
date = {2011-05-01},
journal = {Neurobiol Aging},
volume = {32},
number = {5},
pages = {916--932},
abstract = {Magnetic resonance imaging (MRI) is the principal method for studying structural age-related brain changes in vivo. However, previous research has yielded inconsistent results, precluding understanding of structural changes of the aging brain. This inconsistency is due to methodological differences and/or different aging patterns across samples. To overcome these problems, we tested age effects on 17 different neuroanatomical structures and total brain volume across five samples, of which one was split to further investigate consistency (883 participants). Widespread age-related volume differences were seen consistently across samples. In four of the five samples, all structures, except the brainstem, showed age-related volume differences. The strongest and most consistent effects were found for cerebral cortex, pallidum, putamen and accumbens volume. Total brain volume, cerebral white matter, caudate, hippocampus and the ventricles consistently showed non-linear age functions. Healthy aging appears associated with more widespread and consistent age-related neuroanatomical volume differences than previously believed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Magnetic resonance imaging (MRI) is the principal method for studying structural age-related brain changes in vivo. However, previous research has yielded inconsistent results, precluding understanding of structural changes of the aging brain. This inconsistency is due to methodological differences and/or different aging patterns across samples. To overcome these problems, we tested age effects on 17 different neuroanatomical structures and total brain volume across five samples, of which one was split to further investigate consistency (883 participants). Widespread age-related volume differences were seen consistently across samples. In four of the five samples, all structures, except the brainstem, showed age-related volume differences. The strongest and most consistent effects were found for cerebral cortex, pallidum, putamen and accumbens volume. Total brain volume, cerebral white matter, caudate, hippocampus and the ventricles consistently showed non-linear age functions. Healthy aging appears associated with more widespread and consistent age-related neuroanatomical volume differences than previously believed.
Chen, J Jean; Rosas, H Diana; Salat, David H
Age-associated reductions in cerebral blood flow are independent from regional atrophy Journal Article
In: Neuroimage, vol. 55, no. 2, pp. 468–478, 2011, ISSN: 1095-9572.
@article{pmid21167947,
title = {Age-associated reductions in cerebral blood flow are independent from regional atrophy},
author = {J Jean Chen and H Diana Rosas and David H Salat},
doi = {10.1016/j.neuroimage.2010.12.032},
issn = {1095-9572},
year = {2011},
date = {2011-03-01},
journal = {Neuroimage},
volume = {55},
number = {2},
pages = {468--478},
abstract = {Prior studies have demonstrated decreasing cerebral blood flow (CBF) in normal aging, but the full spatial pattern and potential mechanism of changes in CBF remain to be elucidated. Specifically, existing data have not been entirely consistent regarding the spatial distribution of such changes, potentially a result of neglecting the effect of age-related tissue atrophy in CBF measurements. In this work, we use pulsed arterial-spin labelling to quantify regional CBF in 86 cognitively and physically healthy adults, aged 23 to 88 years. Surface-based analyses were utilized to map regional decline in CBF and cortical thickness with advancing age, and to examine the spatial associations and dissociations between these metrics. Our results demonstrate regionally selective age-related reductions in cortical perfusion, involving the superior-frontal, orbito-frontal, superior-parietal, middle-inferior temporal, insular, precuneus, supramarginal, lateral-occipital and cingulate regions, while subcortical CBF was relatively preserved in aging. Regional effects of age on CBF differed from that of grey-matter atrophy. In addition, the pattern of CBF associations with age displays an interesting similarity with the default-mode network. These findings demonstrate the dissociation between regional CBF and structural alterations specific to normal aging, and augment our understanding of mechanisms of pathology in older adults.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Prior studies have demonstrated decreasing cerebral blood flow (CBF) in normal aging, but the full spatial pattern and potential mechanism of changes in CBF remain to be elucidated. Specifically, existing data have not been entirely consistent regarding the spatial distribution of such changes, potentially a result of neglecting the effect of age-related tissue atrophy in CBF measurements. In this work, we use pulsed arterial-spin labelling to quantify regional CBF in 86 cognitively and physically healthy adults, aged 23 to 88 years. Surface-based analyses were utilized to map regional decline in CBF and cortical thickness with advancing age, and to examine the spatial associations and dissociations between these metrics. Our results demonstrate regionally selective age-related reductions in cortical perfusion, involving the superior-frontal, orbito-frontal, superior-parietal, middle-inferior temporal, insular, precuneus, supramarginal, lateral-occipital and cingulate regions, while subcortical CBF was relatively preserved in aging. Regional effects of age on CBF differed from that of grey-matter atrophy. In addition, the pattern of CBF associations with age displays an interesting similarity with the default-mode network. These findings demonstrate the dissociation between regional CBF and structural alterations specific to normal aging, and augment our understanding of mechanisms of pathology in older adults.
Leritz, Elizabeth C; Salat, David H; Williams, Victoria J; Schnyer, David M; Rudolph, James L; Lipsitz, Lewis; Fischl, Bruce; McGlinchey, Regina E; Milberg, William P
In: Neuroimage, vol. 54, no. 4, pp. 2659–2671, 2011, ISSN: 1095-9572.
@article{pmid21035552,
title = {Thickness of the human cerebral cortex is associated with metrics of cerebrovascular health in a normative sample of community dwelling older adults},
author = {Elizabeth C Leritz and David H Salat and Victoria J Williams and David M Schnyer and James L Rudolph and Lewis Lipsitz and Bruce Fischl and Regina E McGlinchey and William P Milberg},
doi = {10.1016/j.neuroimage.2010.10.050},
issn = {1095-9572},
year = {2011},
date = {2011-02-01},
journal = {Neuroimage},
volume = {54},
number = {4},
pages = {2659--2671},
abstract = {We examined how wide ranges in levels of risk factors for cerebrovascular disease are associated with thickness of the human cerebral cortex in 115 individuals ages 43-83 with no cerebrovascular or neurologic history. Cerebrovascular risk factors included blood pressure, cholesterol, body mass index, creatinine, and diabetes-related factors. Variables were submitted into a principal components analysis that confirmed four orthogonal factors (blood pressure, cholesterol, cholesterol/metabolic and glucose). T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness. Increasing blood pressure factor scores were associated with numerous regions of reduced thickness. Increasing glucose scores were modestly associated with areas of regionally decreased thickness. Increasing cholesterol scores, in contrast, were associated with thicker cortex across the whole brain. All findings were primarily independent of age. These results provide evidence that normal and moderately abnormal levels of parameters used to assess cerebrovascular health may impact brain structure, even in the absence of cerebrovascular disease. Our data have important implications for the clinical management of vascular health, as well as for what is currently conceptualized as "normal aging" as they suggest that subclinical levels of risk may impact cortical gray matter before a disease process is evident.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We examined how wide ranges in levels of risk factors for cerebrovascular disease are associated with thickness of the human cerebral cortex in 115 individuals ages 43-83 with no cerebrovascular or neurologic history. Cerebrovascular risk factors included blood pressure, cholesterol, body mass index, creatinine, and diabetes-related factors. Variables were submitted into a principal components analysis that confirmed four orthogonal factors (blood pressure, cholesterol, cholesterol/metabolic and glucose). T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness. Increasing blood pressure factor scores were associated with numerous regions of reduced thickness. Increasing glucose scores were modestly associated with areas of regionally decreased thickness. Increasing cholesterol scores, in contrast, were associated with thicker cortex across the whole brain. All findings were primarily independent of age. These results provide evidence that normal and moderately abnormal levels of parameters used to assess cerebrovascular health may impact brain structure, even in the absence of cerebrovascular disease. Our data have important implications for the clinical management of vascular health, as well as for what is currently conceptualized as "normal aging" as they suggest that subclinical levels of risk may impact cortical gray matter before a disease process is evident.
Salat, David H
The declining infrastructure of the aging brain Journal Article
In: Brain Connect, vol. 1, no. 4, pp. 279–293, 2011, ISSN: 2158-0022.
@article{pmid22432418,
title = {The declining infrastructure of the aging brain},
author = {David H Salat},
doi = {10.1089/brain.2011.0056},
issn = {2158-0022},
year = {2011},
date = {2011-01-01},
journal = {Brain Connect},
volume = {1},
number = {4},
pages = {279--293},
abstract = {Great effort has been dedicated to mapping the functional architecture of the brain in health and disease. The neural centers that support cognition and behavior are the "hubs" defining the salient geographic landmarks of the cerebral topography. Similar to urban cartography, however, the functionality of these hubs is critically dependent on the infrastructure permitting the transfer of relevant information from site to site, and this infrastructure is susceptible to deterioration. The groundwork of the brain lies in the form of the complexly organized myelinated nerve fibers responsible for the inter-regional transmission of electrical impulses among distinct neural areas. Damage to the myelin sheath and reduction in the total number of nerve fibers with aging are thought to result in a degradation in the efficiency of communication among neural regions and to contribute to the decline of function in older adults. This article describes selected studies that are relevant to understanding the deterioration in structural connectivity of the aging brain with a focus on potential consequences to functional network activity. First, the neural substrates of connectivity and techniques used in the study of connectivity are described with a focus on neuroimaging methodologies. This is followed with discussion of the negative effects of age on connective integrity, and the possible mechanisms and neural and cognitive consequences of this progressive disconnection. Given the potential for natural repair of certain elements of the connective network, understanding the basis of age-associated decline in connectivity could have important implications with regard to the amelioration of neural dysfunction and the restoration of the infrastructure necessary for optimal function in older adults.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Great effort has been dedicated to mapping the functional architecture of the brain in health and disease. The neural centers that support cognition and behavior are the "hubs" defining the salient geographic landmarks of the cerebral topography. Similar to urban cartography, however, the functionality of these hubs is critically dependent on the infrastructure permitting the transfer of relevant information from site to site, and this infrastructure is susceptible to deterioration. The groundwork of the brain lies in the form of the complexly organized myelinated nerve fibers responsible for the inter-regional transmission of electrical impulses among distinct neural areas. Damage to the myelin sheath and reduction in the total number of nerve fibers with aging are thought to result in a degradation in the efficiency of communication among neural regions and to contribute to the decline of function in older adults. This article describes selected studies that are relevant to understanding the deterioration in structural connectivity of the aging brain with a focus on potential consequences to functional network activity. First, the neural substrates of connectivity and techniques used in the study of connectivity are described with a focus on neuroimaging methodologies. This is followed with discussion of the negative effects of age on connective integrity, and the possible mechanisms and neural and cognitive consequences of this progressive disconnection. Given the potential for natural repair of certain elements of the connective network, understanding the basis of age-associated decline in connectivity could have important implications with regard to the amelioration of neural dysfunction and the restoration of the infrastructure necessary for optimal function in older adults.
2010
Ziegler, David A; Piguet, Olivier; Salat, David H; Prince, Keyma; Connally, Emily; Corkin, Suzanne
Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness Journal Article
In: Neurobiol Aging, vol. 31, no. 11, pp. 1912–1926, 2010, ISSN: 1558-1497.
@article{pmid19091444,
title = {Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness},
author = {David A Ziegler and Olivier Piguet and David H Salat and Keyma Prince and Emily Connally and Suzanne Corkin},
doi = {10.1016/j.neurobiolaging.2008.10.015},
issn = {1558-1497},
year = {2010},
date = {2010-11-01},
journal = {Neurobiol Aging},
volume = {31},
number = {11},
pages = {1912--1926},
abstract = {It is well established that healthy aging is accompanied by structural changes in many brain regions and functional decline in a number of cognitive domains. The goal of this study was to determine (1) whether the regional distribution of age-related brain changes is similar in gray matter (GM) and white matter (WM) regions, or whether these two tissue types are affected differently by aging, and (2) whether measures of cognitive performance are more closely linked to alterations in the cerebral cortex or in the underlying WM in older adults (OA). To address these questions, we collected high-resolution magnetic resonance imaging (MRI) data from a large sample of healthy young adults (YA; aged 18-28) and OA (aged 61-86 years). In addition, the OA completed a series of tasks selected to assess cognition in three domains: cognitive control, episodic memory, and semantic memory. Using advanced techniques for measuring cortical thickness and WM integrity, we found that healthy aging was accompanied by deterioration of both GM and WM, but with distinct patterns of change: Cortical thinning occurred primarily in primary sensory and motor cortices, whereas WM changes were localized to regions underlying association cortices. Further, in OA, we found a striking pattern of region-specific correlations between measures of cognitive performance and WM integrity, but not cortical thickness. Specifically, cognitive control correlated with integrity of frontal lobe WM, whereas episodic memory was related to integrity of temporal and parietal lobe WM. Thus, age-related impairments in specific cognitive capacities may arise from degenerative processes that affect the underlying connections of their respective neural networks.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
It is well established that healthy aging is accompanied by structural changes in many brain regions and functional decline in a number of cognitive domains. The goal of this study was to determine (1) whether the regional distribution of age-related brain changes is similar in gray matter (GM) and white matter (WM) regions, or whether these two tissue types are affected differently by aging, and (2) whether measures of cognitive performance are more closely linked to alterations in the cerebral cortex or in the underlying WM in older adults (OA). To address these questions, we collected high-resolution magnetic resonance imaging (MRI) data from a large sample of healthy young adults (YA; aged 18-28) and OA (aged 61-86 years). In addition, the OA completed a series of tasks selected to assess cognition in three domains: cognitive control, episodic memory, and semantic memory. Using advanced techniques for measuring cortical thickness and WM integrity, we found that healthy aging was accompanied by deterioration of both GM and WM, but with distinct patterns of change: Cortical thinning occurred primarily in primary sensory and motor cortices, whereas WM changes were localized to regions underlying association cortices. Further, in OA, we found a striking pattern of region-specific correlations between measures of cognitive performance and WM integrity, but not cortical thickness. Specifically, cognitive control correlated with integrity of frontal lobe WM, whereas episodic memory was related to integrity of temporal and parietal lobe WM. Thus, age-related impairments in specific cognitive capacities may arise from degenerative processes that affect the underlying connections of their respective neural networks.
Dierksen, Gregory A; Skehan, Maureen E; Khan, Muhammad A; Jeng, Jed; Nandigam, R N Kaveer; Becker, John A; Kumar, Ashok; Neal, Krista L; Betensky, Rebecca A; Frosch, Matthew P; Rosand, Jonathan; Johnson, Keith A; Viswanathan, Anand; Salat, David H; Greenberg, Steven M
Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy Journal Article
In: Ann Neurol, vol. 68, no. 4, pp. 545–548, 2010, ISSN: 1531-8249.
@article{pmid20865701,
title = {Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy},
author = {Gregory A Dierksen and Maureen E Skehan and Muhammad A Khan and Jed Jeng and R N Kaveer Nandigam and John A Becker and Ashok Kumar and Krista L Neal and Rebecca A Betensky and Matthew P Frosch and Jonathan Rosand and Keith A Johnson and Anand Viswanathan and David H Salat and Steven M Greenberg},
doi = {10.1002/ana.22099},
issn = {1531-8249},
year = {2010},
date = {2010-10-01},
journal = {Ann Neurol},
volume = {68},
number = {4},
pages = {545--548},
abstract = {Advanced cerebrovascular β-amyloid deposition (cerebral amyloid angiopathy, CAA) is associated with cerebral microbleeds, but the precise relationship between CAA burden and microbleeds is undefined. We used T2*-weighted magnetic resonance imaging (MRI) and noninvasive amyloid imaging with Pittsburgh Compound B (PiB) to analyze the spatial relationship between CAA and microbleeds. On coregistered positron emission tomography (PET) and MRI images, PiB retention was increased at microbleed sites compared to simulated control lesions (p = 0.002) and declined with increasing distance from the microbleed (p < 0.0001). These findings indicate that microbleeds occur preferentially in local regions of concentrated amyloid and support therapeutic strategies aimed at reducing vascular amyloid deposition.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Advanced cerebrovascular β-amyloid deposition (cerebral amyloid angiopathy, CAA) is associated with cerebral microbleeds, but the precise relationship between CAA burden and microbleeds is undefined. We used T2*-weighted magnetic resonance imaging (MRI) and noninvasive amyloid imaging with Pittsburgh Compound B (PiB) to analyze the spatial relationship between CAA and microbleeds. On coregistered positron emission tomography (PET) and MRI images, PiB retention was increased at microbleed sites compared to simulated control lesions (p = 0.002) and declined with increasing distance from the microbleed (p < 0.0001). These findings indicate that microbleeds occur preferentially in local regions of concentrated amyloid and support therapeutic strategies aimed at reducing vascular amyloid deposition.
Desikan, Rahul S; Sabuncu, Mert R; Schmansky, Nicholas J; Reuter, Martin; Cabral, Howard J; Hess, Christopher P; Weiner, Michael W; Biffi, Alessandro; Anderson, Christopher D; Rosand, Jonathan; Salat, David H; Kemper, Thomas L; Dale, Anders M; Sperling, Reisa A; and, Bruce Fischl
Selective disruption of the cerebral neocortex in Alzheimer's disease Journal Article
In: PLoS One, vol. 5, no. 9, pp. e12853, 2010, ISSN: 1932-6203.
@article{pmid20886094,
title = {Selective disruption of the cerebral neocortex in Alzheimer's disease},
author = {Rahul S Desikan and Mert R Sabuncu and Nicholas J Schmansky and Martin Reuter and Howard J Cabral and Christopher P Hess and Michael W Weiner and Alessandro Biffi and Christopher D Anderson and Jonathan Rosand and David H Salat and Thomas L Kemper and Anders M Dale and Reisa A Sperling and Bruce Fischl and },
doi = {10.1371/journal.pone.0012853},
issn = {1932-6203},
year = {2010},
date = {2010-09-01},
journal = {PLoS One},
volume = {5},
number = {9},
pages = {e12853},
abstract = {BACKGROUND: Alzheimer's disease (AD) and its transitional state mild cognitive impairment (MCI) are characterized by amyloid plaque and tau neurofibrillary tangle (NFT) deposition within the cerebral neocortex and neuronal loss within the hippocampal formation. However, the precise relationship between pathologic changes in neocortical regions and hippocampal atrophy is largely unknown.nnMETHODOLOGY/PRINCIPAL FINDINGS: In this study, combining structural MRI scans and automated image analysis tools with reduced cerebrospinal fluid (CSF) Aβ levels, a surrogate for intra-cranial amyloid plaques and elevated CSF phosphorylated tau (p-tau) levels, a surrogate for neocortical NFTs, we examined the relationship between the presence of Alzheimer's pathology, gray matter thickness of select neocortical regions, and hippocampal volume in cognitively normal older participants and individuals with MCI and AD (n = 724). Amongst all 3 groups, only select heteromodal cortical regions significantly correlated with hippocampal volume. Amongst MCI and AD individuals, gray matter thickness of the entorhinal cortex and inferior temporal gyrus significantly predicted longitudinal hippocampal volume loss in both amyloid positive and p-tau positive individuals. Amongst cognitively normal older adults, thinning only within the medial portion of the orbital frontal cortex significantly differentiated amyloid positive from amyloid negative individuals whereas thinning only within the entorhinal cortex significantly discriminated p-tau positive from p-tau negative individuals.nnCONCLUSIONS/SIGNIFICANCE: Cortical Aβ and tau pathology affects gray matter thinning within select neocortical regions and potentially contributes to downstream hippocampal degeneration. Neocortical Alzheimer's pathology is evident even amongst older asymptomatic individuals suggesting the existence of a preclinical phase of dementia.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Alzheimer's disease (AD) and its transitional state mild cognitive impairment (MCI) are characterized by amyloid plaque and tau neurofibrillary tangle (NFT) deposition within the cerebral neocortex and neuronal loss within the hippocampal formation. However, the precise relationship between pathologic changes in neocortical regions and hippocampal atrophy is largely unknown.nnMETHODOLOGY/PRINCIPAL FINDINGS: In this study, combining structural MRI scans and automated image analysis tools with reduced cerebrospinal fluid (CSF) Aβ levels, a surrogate for intra-cranial amyloid plaques and elevated CSF phosphorylated tau (p-tau) levels, a surrogate for neocortical NFTs, we examined the relationship between the presence of Alzheimer's pathology, gray matter thickness of select neocortical regions, and hippocampal volume in cognitively normal older participants and individuals with MCI and AD (n = 724). Amongst all 3 groups, only select heteromodal cortical regions significantly correlated with hippocampal volume. Amongst MCI and AD individuals, gray matter thickness of the entorhinal cortex and inferior temporal gyrus significantly predicted longitudinal hippocampal volume loss in both amyloid positive and p-tau positive individuals. Amongst cognitively normal older adults, thinning only within the medial portion of the orbital frontal cortex significantly differentiated amyloid positive from amyloid negative individuals whereas thinning only within the entorhinal cortex significantly discriminated p-tau positive from p-tau negative individuals.nnCONCLUSIONS/SIGNIFICANCE: Cortical Aβ and tau pathology affects gray matter thinning within select neocortical regions and potentially contributes to downstream hippocampal degeneration. Neocortical Alzheimer's pathology is evident even amongst older asymptomatic individuals suggesting the existence of a preclinical phase of dementia.
Desikan, Rahul S; Cabral, Howard J; Settecase, Fabio; Hess, Christopher P; Dillon, William P; Glastonbury, Christine M; Weiner, Michael W; Schmansky, Nicholas J; Salat, David H; and, Bruce Fischl
Automated MRI measures predict progression to Alzheimer's disease Journal Article
In: Neurobiol Aging, vol. 31, no. 8, pp. 1364–1374, 2010, ISSN: 1558-1497.
@article{pmid20570399,
title = {Automated MRI measures predict progression to Alzheimer's disease},
author = {Rahul S Desikan and Howard J Cabral and Fabio Settecase and Christopher P Hess and William P Dillon and Christine M Glastonbury and Michael W Weiner and Nicholas J Schmansky and David H Salat and Bruce Fischl and },
doi = {10.1016/j.neurobiolaging.2010.04.023},
issn = {1558-1497},
year = {2010},
date = {2010-08-01},
journal = {Neurobiol Aging},
volume = {31},
number = {8},
pages = {1364--1374},
abstract = {The prediction of individuals with mild cognitive impairment (MCI) destined to develop Alzheimer's disease (AD) is of increasing clinical importance. In this study, using baseline T1-weighted MRI scans of 324 MCI individuals from two cohorts and automated software tools, we employed factor analyses and Cox proportional hazards models to identify a set of neuroanatomic measures that best predicted the time to progress from MCI to AD. For comparison, cerebrospinal fluid (CSF) assessments of cellular pathology and positron emission tomography (PET) measures of metabolic activity were additionally examined. By 3 years follow-up, 60 MCI individuals from the first cohort and 58 MCI individuals from the second cohort had progressed to a diagnosis of AD. Cox models on the first cohort demonstrated significant effects for the medial temporal factor [Hazards Ratio (HR) = 0.43{95% confidence interval (CI), 0.32-0.55}, p < 0.0001], the fronto-parietoccipital factor [HR = 0.59{95% CI, 0.48-0.80}, p < 0.001], and the lateral temporal factor [HR = 0.67 {95% CI, 0.52-0.87}, p < 0.01]. When applied to the second cohort, these Cox models showed significant effects for the medial temporal factor [HR = 0.44 {0.32-0.61}, p < 0.001] and lateral temporal factor [HR = 0.49 {0.38-0.62}, p < 0.001]. In a combined Cox model, consisting of individual CSF, PET, and MRI measures that best predicted disease progression, only the medial temporal factor [HR = 0.53 {95% CI, 0.34-0.81}, p < 0.001] demonstrated a significant effect. These findings illustrate that automated MRI measures of the medial temporal cortex accurately and reliably predict time to disease progression, outperform cellular and metabolic measures as predictors of clinical decline, and can potentially serve as a predictive marker for AD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The prediction of individuals with mild cognitive impairment (MCI) destined to develop Alzheimer's disease (AD) is of increasing clinical importance. In this study, using baseline T1-weighted MRI scans of 324 MCI individuals from two cohorts and automated software tools, we employed factor analyses and Cox proportional hazards models to identify a set of neuroanatomic measures that best predicted the time to progress from MCI to AD. For comparison, cerebrospinal fluid (CSF) assessments of cellular pathology and positron emission tomography (PET) measures of metabolic activity were additionally examined. By 3 years follow-up, 60 MCI individuals from the first cohort and 58 MCI individuals from the second cohort had progressed to a diagnosis of AD. Cox models on the first cohort demonstrated significant effects for the medial temporal factor [Hazards Ratio (HR) = 0.43{95% confidence interval (CI), 0.32-0.55}, p < 0.0001], the fronto-parietoccipital factor [HR = 0.59{95% CI, 0.48-0.80}, p < 0.001], and the lateral temporal factor [HR = 0.67 {95% CI, 0.52-0.87}, p < 0.01]. When applied to the second cohort, these Cox models showed significant effects for the medial temporal factor [HR = 0.44 {0.32-0.61}, p < 0.001] and lateral temporal factor [HR = 0.49 {0.38-0.62}, p < 0.001]. In a combined Cox model, consisting of individual CSF, PET, and MRI measures that best predicted disease progression, only the medial temporal factor [HR = 0.53 {95% CI, 0.34-0.81}, p < 0.001] demonstrated a significant effect. These findings illustrate that automated MRI measures of the medial temporal cortex accurately and reliably predict time to disease progression, outperform cellular and metabolic measures as predictors of clinical decline, and can potentially serve as a predictive marker for AD.
Leritz, Elizabeth C; Salat, David H; Milberg, William P; Williams, Victoria J; Chapman, Caroline E; Grande, Laura J; Rudolph, James L; Schnyer, David M; Barber, Colleen E; Lipsitz, Lewis A; McGlinchey, Regina E
Variation in blood pressure is associated with white matter microstructure but not cognition in African Americans Journal Article
In: Neuropsychology, vol. 24, no. 2, pp. 199–208, 2010, ISSN: 1931-1559.
@article{pmid20230114,
title = {Variation in blood pressure is associated with white matter microstructure but not cognition in African Americans},
author = {Elizabeth C Leritz and David H Salat and William P Milberg and Victoria J Williams and Caroline E Chapman and Laura J Grande and James L Rudolph and David M Schnyer and Colleen E Barber and Lewis A Lipsitz and Regina E McGlinchey},
doi = {10.1037/a0018108},
issn = {1931-1559},
year = {2010},
date = {2010-03-01},
journal = {Neuropsychology},
volume = {24},
number = {2},
pages = {199--208},
abstract = {Although hypertension is a major risk factor for cerebrovascular disease (CVD) and is highly prevalent in African Americans, little is known about how blood pressure (BP) affects brain-behavior relationships in this population. In predominantly Caucasian populations, high BP is associated with alterations in frontal-subcortical white matter and in executive functioning aspects of cognition. We investigated associations among BP, brain structure, and neuropsychological functioning in 52 middle-older-age African Americans without diagnosed history of CVD. All participants underwent diffusion tensor imaging for examination of white matter integrity, indexed by fractional anisotropy (FA). Three regions of interest were derived in the anterior (genu) and posterior (splenium) corpus callosum and across the whole brain. A brief neuropsychological battery was administered from which composite scores of executive function and memory were derived. Blood pressure was characterized by mean arterial blood pressure (MABP). When controlling for age, higher MABP was associated with lower FA in the genu, and there was a trend for this same relationship with regard to whole-brain FA. When the sample was broken into groups on the basis of treatment for BP regulation (medicated vs. nonmedicated), MABP was related to genu and whole-brain FA only in the nonmedicated group. Neither MABP nor FA was significantly related to either neuropsychological composite score regardless of medication use. These data provide important evidence that variation in BP may contribute to significant alterations in specific neural regions of white matter in nonmedicated individuals without symptoms of overt CVD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Although hypertension is a major risk factor for cerebrovascular disease (CVD) and is highly prevalent in African Americans, little is known about how blood pressure (BP) affects brain-behavior relationships in this population. In predominantly Caucasian populations, high BP is associated with alterations in frontal-subcortical white matter and in executive functioning aspects of cognition. We investigated associations among BP, brain structure, and neuropsychological functioning in 52 middle-older-age African Americans without diagnosed history of CVD. All participants underwent diffusion tensor imaging for examination of white matter integrity, indexed by fractional anisotropy (FA). Three regions of interest were derived in the anterior (genu) and posterior (splenium) corpus callosum and across the whole brain. A brief neuropsychological battery was administered from which composite scores of executive function and memory were derived. Blood pressure was characterized by mean arterial blood pressure (MABP). When controlling for age, higher MABP was associated with lower FA in the genu, and there was a trend for this same relationship with regard to whole-brain FA. When the sample was broken into groups on the basis of treatment for BP regulation (medicated vs. nonmedicated), MABP was related to genu and whole-brain FA only in the nonmedicated group. Neither MABP nor FA was significantly related to either neuropsychological composite score regardless of medication use. These data provide important evidence that variation in BP may contribute to significant alterations in specific neural regions of white matter in nonmedicated individuals without symptoms of overt CVD.
Rosas, H Diana; Lee, Stephanie Y; Bender, Alexander C; Zaleta, Alexandra K; Vangel, Mark; Yu, Peng; Fischl, Bruce; Pappu, Vasanth; Onorato, Christina; Cha, Jang-Ho; Salat, David H; Hersch, Steven M
Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical "disconnection" Journal Article
In: Neuroimage, vol. 49, no. 4, pp. 2995–3004, 2010, ISSN: 1095-9572.
@article{pmid19850138,
title = {Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical "disconnection"},
author = {H Diana Rosas and Stephanie Y Lee and Alexander C Bender and Alexandra K Zaleta and Mark Vangel and Peng Yu and Bruce Fischl and Vasanth Pappu and Christina Onorato and Jang-Ho Cha and David H Salat and Steven M Hersch},
doi = {10.1016/j.neuroimage.2009.10.015},
issn = {1095-9572},
year = {2010},
date = {2010-02-01},
journal = {Neuroimage},
volume = {49},
number = {4},
pages = {2995--3004},
abstract = {The corpus callosum (CC) is the major conduit for information transfer between the cerebral hemispheres and plays an integral role in relaying sensory, motor and cognitive information between homologous cortical regions. The majority of fibers that make up the CC arise from large pyramidal neurons in layers III and V, which project contra-laterally. These neurons degenerate in Huntington's disease (HD) in a topographically and temporally selective way. Since any focus of cortical degeneration could be expected to secondarily de-afferent homologous regions of cortex, we hypothesized that regionally selective cortical degeneration would be reflected in regionally selective degeneration of the CC. We used conventional T1-weighted, diffusion tensor imaging (DTI), and a modified corpus callosum segmentation scheme to examine the CC in healthy controls, huntingtin gene-carriers and symptomatic HD subjects. We measured mid-sagittal callosal cross-sectional thickness and several DTI parameters, including fractional anisotropy (FA), which reflects the degree of white matter organization, radial diffusivity, a suggested index of myelin integrity, and axial diffusivity, a suggested index of axonal damage of the CC. We found a topologically selective pattern of alterations in these measures in pre-manifest subjects that were more extensive in early symptomatic HD subjects and that correlated with performance on distinct cognitive measures, suggesting an important role for disrupted inter-hemispheric transfer in the clinical symptoms of HD. Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The corpus callosum (CC) is the major conduit for information transfer between the cerebral hemispheres and plays an integral role in relaying sensory, motor and cognitive information between homologous cortical regions. The majority of fibers that make up the CC arise from large pyramidal neurons in layers III and V, which project contra-laterally. These neurons degenerate in Huntington's disease (HD) in a topographically and temporally selective way. Since any focus of cortical degeneration could be expected to secondarily de-afferent homologous regions of cortex, we hypothesized that regionally selective cortical degeneration would be reflected in regionally selective degeneration of the CC. We used conventional T1-weighted, diffusion tensor imaging (DTI), and a modified corpus callosum segmentation scheme to examine the CC in healthy controls, huntingtin gene-carriers and symptomatic HD subjects. We measured mid-sagittal callosal cross-sectional thickness and several DTI parameters, including fractional anisotropy (FA), which reflects the degree of white matter organization, radial diffusivity, a suggested index of myelin integrity, and axial diffusivity, a suggested index of axonal damage of the CC. We found a topologically selective pattern of alterations in these measures in pre-manifest subjects that were more extensive in early symptomatic HD subjects and that correlated with performance on distinct cognitive measures, suggesting an important role for disrupted inter-hemispheric transfer in the clinical symptoms of HD. Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing.
2009
Fjell, Anders M; Westlye, Lars T; Amlien, Inge; Espeseth, Thomas; Reinvang, Ivar; Raz, Naftali; Agartz, Ingrid; Salat, David H; Greve, Doug N; Fischl, Bruce; Dale, Anders M; Walhovd, Kristine B
High consistency of regional cortical thinning in aging across multiple samples Journal Article
In: Cereb Cortex, vol. 19, no. 9, pp. 2001–2012, 2009, ISSN: 1460-2199.
@article{pmid19150922,
title = {High consistency of regional cortical thinning in aging across multiple samples},
author = {Anders M Fjell and Lars T Westlye and Inge Amlien and Thomas Espeseth and Ivar Reinvang and Naftali Raz and Ingrid Agartz and David H Salat and Doug N Greve and Bruce Fischl and Anders M Dale and Kristine B Walhovd},
doi = {10.1093/cercor/bhn232},
issn = {1460-2199},
year = {2009},
date = {2009-09-01},
journal = {Cereb Cortex},
volume = {19},
number = {9},
pages = {2001--2012},
abstract = {Cross-sectional magnetic resonance imaging (MRI) studies of cortical thickness and volume have shown age effects on large areas, but there are substantial discrepancies across studies regarding the localization and magnitude of effects. These discrepancies hinder understanding of effects of aging on brain morphometry, and limit the potential usefulness of MR in research on healthy and pathological age-related brain changes. The present study was undertaken to overcome this problem by assessing the consistency of age effects on cortical thickness across 6 different samples with a total of 883 participants. A surface-based segmentation procedure (FreeSurfer) was used to calculate cortical thickness continuously across the brain surface. The results showed consistent age effects across samples in the superior, middle, and inferior frontal gyri, superior and middle temporal gyri, precuneus, inferior and superior parietal cortices, fusiform and lingual gyri, and the temporo-parietal junction. The strongest effects were seen in the superior and inferior frontal gyri, as well as superior parts of the temporal lobe. The inferior temporal lobe and anterior cingulate cortices were relatively less affected by age. The results are discussed in relation to leading theories of cognitive aging.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cross-sectional magnetic resonance imaging (MRI) studies of cortical thickness and volume have shown age effects on large areas, but there are substantial discrepancies across studies regarding the localization and magnitude of effects. These discrepancies hinder understanding of effects of aging on brain morphometry, and limit the potential usefulness of MR in research on healthy and pathological age-related brain changes. The present study was undertaken to overcome this problem by assessing the consistency of age effects on cortical thickness across 6 different samples with a total of 883 participants. A surface-based segmentation procedure (FreeSurfer) was used to calculate cortical thickness continuously across the brain surface. The results showed consistent age effects across samples in the superior, middle, and inferior frontal gyri, superior and middle temporal gyri, precuneus, inferior and superior parietal cortices, fusiform and lingual gyri, and the temporo-parietal junction. The strongest effects were seen in the superior and inferior frontal gyri, as well as superior parts of the temporal lobe. The inferior temporal lobe and anterior cingulate cortices were relatively less affected by age. The results are discussed in relation to leading theories of cognitive aging.
Knake, Susanne; Salat, David H; Halgren, Eric; Halko, Mark A; Greve, Douglas N; Grant, P Ellen
Changes in white matter microstructure in patients with TLE and hippocampal sclerosis Journal Article
In: Epileptic Disord, vol. 11, no. 3, pp. 244–250, 2009, ISSN: 1294-9361.
@article{pmid19736169,
title = {Changes in white matter microstructure in patients with TLE and hippocampal sclerosis},
author = {Susanne Knake and David H Salat and Eric Halgren and Mark A Halko and Douglas N Greve and P Ellen Grant},
doi = {10.1684/epd.2009.0272},
issn = {1294-9361},
year = {2009},
date = {2009-09-01},
journal = {Epileptic Disord},
volume = {11},
number = {3},
pages = {244--250},
abstract = {OBJECTIVE: Patients with mesial temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often show ictal and interictal propagation of epileptiform EEG activity to the ipsilateral temporal neocortex, the ipsilateral frontal lobe or the contralateral hippocampus, although structural MRI only shows unilateral involvement of the hippocampal formation. We used whole-head diffusion Tensor Imaging (DTI) to delineate a network that facilitates propagation of interictal epileptiform and seizure activity in this patient group.nnMETHODS: Isotropic 2 mm DTI was performed at 3 Tesla in 12 patients with medically intractable left TLE due to HS and compared to 12 controls. Whole-brain maps of fractional anisotropy (FA) were compared using a voxel based t-test to search for regions affected in patients with HS. This preliminary analysis was complementary to a set of anatomically guided region of interest (ROI) analyses that were manually defined on each individual's FA map.nnRESULTS: Left HS patients showed FA decreases in the temporal lobe white matter bilaterally, the ipsilateral frontal lobe white matter (WM) and in the genu and trunk of the corpus callosum. ROI analysis identified a significant FA decrease in left HS subjects in the affected hippocampus, WM of the ipsilateral parahippocampal gyrus and the genu and trunk of the corpus callosum.nnCONCLUSION: WM alterations occur bilaterally in the temporal lobe and in the ipsilateral superior frontal gyrus in left HS. The etiology and significance of these changes are unclear but the role of these regions in epileptogenesis and for pathways of epileptic spread should be further investigated.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Patients with mesial temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often show ictal and interictal propagation of epileptiform EEG activity to the ipsilateral temporal neocortex, the ipsilateral frontal lobe or the contralateral hippocampus, although structural MRI only shows unilateral involvement of the hippocampal formation. We used whole-head diffusion Tensor Imaging (DTI) to delineate a network that facilitates propagation of interictal epileptiform and seizure activity in this patient group.nnMETHODS: Isotropic 2 mm DTI was performed at 3 Tesla in 12 patients with medically intractable left TLE due to HS and compared to 12 controls. Whole-brain maps of fractional anisotropy (FA) were compared using a voxel based t-test to search for regions affected in patients with HS. This preliminary analysis was complementary to a set of anatomically guided region of interest (ROI) analyses that were manually defined on each individual's FA map.nnRESULTS: Left HS patients showed FA decreases in the temporal lobe white matter bilaterally, the ipsilateral frontal lobe white matter (WM) and in the genu and trunk of the corpus callosum. ROI analysis identified a significant FA decrease in left HS subjects in the affected hippocampus, WM of the ipsilateral parahippocampal gyrus and the genu and trunk of the corpus callosum.nnCONCLUSION: WM alterations occur bilaterally in the temporal lobe and in the ipsilateral superior frontal gyrus in left HS. The etiology and significance of these changes are unclear but the role of these regions in epileptogenesis and for pathways of epileptic spread should be further investigated.
Fischl, Bruce; Stevens, Allison A; Rajendran, Niranjini; Yeo, B T Thomas; Greve, Douglas N; Leemput, Koen Van; Polimeni, Jonathan R; Kakunoori, Sita; Buckner, Randy L; Pacheco, Jennifer; Salat, David H; Melcher, Jennifer; Frosch, Matthew P; Hyman, Bradley T; Grant, P Ellen; Rosen, Bruce R; van der Kouwe, André J W; Wiggins, Graham C; Wald, Lawrence L; Augustinack, Jean C
Predicting the location of entorhinal cortex from MRI Journal Article
In: Neuroimage, vol. 47, no. 1, pp. 8–17, 2009, ISSN: 1095-9572.
@article{pmid19376238,
title = {Predicting the location of entorhinal cortex from MRI},
author = {Bruce Fischl and Allison A Stevens and Niranjini Rajendran and B T Thomas Yeo and Douglas N Greve and Koen Van Leemput and Jonathan R Polimeni and Sita Kakunoori and Randy L Buckner and Jennifer Pacheco and David H Salat and Jennifer Melcher and Matthew P Frosch and Bradley T Hyman and P Ellen Grant and Bruce R Rosen and André J W van der Kouwe and Graham C Wiggins and Lawrence L Wald and Jean C Augustinack},
doi = {10.1016/j.neuroimage.2009.04.033},
issn = {1095-9572},
year = {2009},
date = {2009-08-01},
journal = {Neuroimage},
volume = {47},
number = {1},
pages = {8--17},
abstract = {Entorhinal cortex (EC) is a medial temporal lobe area critical to memory formation and spatial navigation that is among the earliest parts of the brain affected by Alzheimer's disease (AD). Accurate localization of EC would thus greatly facilitate early detection and diagnosis of AD. In this study, we used ultra-high resolution ex vivo MRI to directly visualize the architectonic features that define EC rostrocaudally and mediolaterally, then applied surface-based registration techniques to quantify the variability of EC with respect to cortical geometry, and made predictions of its location on in vivo scans. The results indicate that EC can be localized quite accurately based on cortical folding patterns, within 3 mm in vivo, a significant step forward in our ability to detect the earliest effects of AD when clinical intervention is most likely to be effective.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Entorhinal cortex (EC) is a medial temporal lobe area critical to memory formation and spatial navigation that is among the earliest parts of the brain affected by Alzheimer's disease (AD). Accurate localization of EC would thus greatly facilitate early detection and diagnosis of AD. In this study, we used ultra-high resolution ex vivo MRI to directly visualize the architectonic features that define EC rostrocaudally and mediolaterally, then applied surface-based registration techniques to quantify the variability of EC with respect to cortical geometry, and made predictions of its location on in vivo scans. The results indicate that EC can be localized quite accurately based on cortical folding patterns, within 3 mm in vivo, a significant step forward in our ability to detect the earliest effects of AD when clinical intervention is most likely to be effective.
Desikan, Rahul S; Cabral, Howard J; Hess, Christopher P; Dillon, William P; Glastonbury, Christine M; Weiner, Michael W; Schmansky, Nicholas J; Greve, Douglas N; Salat, David H; Buckner, Randy L; and, Bruce Fischl
Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease Journal Article
In: Brain, vol. 132, no. Pt 8, pp. 2048–2057, 2009, ISSN: 1460-2156.
@article{pmid19460794,
title = {Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease},
author = {Rahul S Desikan and Howard J Cabral and Christopher P Hess and William P Dillon and Christine M Glastonbury and Michael W Weiner and Nicholas J Schmansky and Douglas N Greve and David H Salat and Randy L Buckner and Bruce Fischl and },
doi = {10.1093/brain/awp123},
issn = {1460-2156},
year = {2009},
date = {2009-08-01},
journal = {Brain},
volume = {132},
number = {Pt 8},
pages = {2048--2057},
abstract = {Mild cognitive impairment can represent a transitional state between normal ageing and Alzheimer's disease. Non-invasive diagnostic methods are needed to identify mild cognitive impairment individuals for early therapeutic interventions. Our objective was to determine whether automated magnetic resonance imaging-based measures could identify mild cognitive impairment individuals with a high degree of accuracy. Baseline volumetric T1-weighted magnetic resonance imaging scans of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with mild cognitive impairment, while the second cohort included 94 older controls and 57 mild cognitive impairment individuals. Sixty-five patients with probable Alzheimer's disease were also included for comparison. For the discrimination of mild cognitive impairment, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94%, sensitivity 74%, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91%, sensitivity 90%, positive likelihood ratio 10.0, negative likelihood ratio 0.11) for the second cohort. For the discrimination of Alzheimer's disease, these three measures demonstrated an area under the curve of 1.0. The three magnetic resonance imaging measures demonstrated significant correlations with clinical and neuropsychological assessments as well as with cerebrospinal fluid levels of tau, hyperphosphorylated tau and abeta 42 proteins. These results demonstrate that automated magnetic resonance imaging measures can serve as an in vivo surrogate for disease severity, underlying neuropathology and as a non-invasive diagnostic method for mild cognitive impairment and Alzheimer's disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mild cognitive impairment can represent a transitional state between normal ageing and Alzheimer's disease. Non-invasive diagnostic methods are needed to identify mild cognitive impairment individuals for early therapeutic interventions. Our objective was to determine whether automated magnetic resonance imaging-based measures could identify mild cognitive impairment individuals with a high degree of accuracy. Baseline volumetric T1-weighted magnetic resonance imaging scans of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with mild cognitive impairment, while the second cohort included 94 older controls and 57 mild cognitive impairment individuals. Sixty-five patients with probable Alzheimer's disease were also included for comparison. For the discrimination of mild cognitive impairment, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94%, sensitivity 74%, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91%, sensitivity 90%, positive likelihood ratio 10.0, negative likelihood ratio 0.11) for the second cohort. For the discrimination of Alzheimer's disease, these three measures demonstrated an area under the curve of 1.0. The three magnetic resonance imaging measures demonstrated significant correlations with clinical and neuropsychological assessments as well as with cerebrospinal fluid levels of tau, hyperphosphorylated tau and abeta 42 proteins. These results demonstrate that automated magnetic resonance imaging measures can serve as an in vivo surrogate for disease severity, underlying neuropathology and as a non-invasive diagnostic method for mild cognitive impairment and Alzheimer's disease.
Fjell, Anders M; Westlye, Lars T; Amlien, Inge; Espeseth, Thomas; Reinvang, Ivar; Raz, Naftali; Agartz, Ingrid; Salat, David H; Greve, Doug N; Fischl, Bruce; Dale, Anders M; Walhovd, Kristine B
Minute effects of sex on the aging brain: a multisample magnetic resonance imaging study of healthy aging and Alzheimer's disease Journal Article
In: J Neurosci, vol. 29, no. 27, pp. 8774–8783, 2009, ISSN: 1529-2401.
@article{pmid19587284,
title = {Minute effects of sex on the aging brain: a multisample magnetic resonance imaging study of healthy aging and Alzheimer's disease},
author = {Anders M Fjell and Lars T Westlye and Inge Amlien and Thomas Espeseth and Ivar Reinvang and Naftali Raz and Ingrid Agartz and David H Salat and Doug N Greve and Bruce Fischl and Anders M Dale and Kristine B Walhovd},
doi = {10.1523/JNEUROSCI.0115-09.2009},
issn = {1529-2401},
year = {2009},
date = {2009-07-01},
journal = {J Neurosci},
volume = {29},
number = {27},
pages = {8774--8783},
abstract = {Age is associated with substantial macrostructural brain changes. While some recent magnetic resonance imaging studies have reported larger age effects in men than women, others find no sex differences. As brain morphometry is a potentially important tool in diagnosis and monitoring of age-related neurological diseases, e.g., Alzheimer's disease (AD), it is important to know whether sex influences brain aging. We analyzed cross-sectional magnetic resonance scans from 1143 healthy participants from seven subsamples provided by four independent research groups. In addition, 96 patients with mild AD were included. Estimates of cortical thickness continuously across the brain surface, as well as volume of 17 subcortical structures, were obtained by use of automated segmentation tools (FreeSurfer). In the healthy participants, no differences in aging slopes between women and men were found in any part of the cortex. Pallidum corrected for intracranial volume showed slightly higher age correlations for men. The analyses were repeated in each of the seven subsamples, and the lack of age x sex interactions was largely replicated. Analyses of the AD sample showed no interactions between sex and age for any brain region. We conclude that sex has negligible effects on the age slope of brain volumes both in healthy participants and in AD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Age is associated with substantial macrostructural brain changes. While some recent magnetic resonance imaging studies have reported larger age effects in men than women, others find no sex differences. As brain morphometry is a potentially important tool in diagnosis and monitoring of age-related neurological diseases, e.g., Alzheimer's disease (AD), it is important to know whether sex influences brain aging. We analyzed cross-sectional magnetic resonance scans from 1143 healthy participants from seven subsamples provided by four independent research groups. In addition, 96 patients with mild AD were included. Estimates of cortical thickness continuously across the brain surface, as well as volume of 17 subcortical structures, were obtained by use of automated segmentation tools (FreeSurfer). In the healthy participants, no differences in aging slopes between women and men were found in any part of the cortex. Pallidum corrected for intracranial volume showed slightly higher age correlations for men. The analyses were repeated in each of the seven subsamples, and the lack of age x sex interactions was largely replicated. Analyses of the AD sample showed no interactions between sex and age for any brain region. We conclude that sex has negligible effects on the age slope of brain volumes both in healthy participants and in AD.
Dickerson, Bradford C; Bakkour, Akram; Salat, David H; Feczko, Eric; Pacheco, Jenni; Greve, Douglas N; Grodstein, Fran; Wright, Christopher I; Blacker, Deborah; Rosas, H Diana; Sperling, Reisa A; Atri, Alireza; Growdon, John H; Hyman, Bradley T; Morris, John C; Fischl, Bruce; Buckner, Randy L
In: Cereb Cortex, vol. 19, no. 3, pp. 497–510, 2009, ISSN: 1460-2199.
@article{pmid18632739,
title = {The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals},
author = {Bradford C Dickerson and Akram Bakkour and David H Salat and Eric Feczko and Jenni Pacheco and Douglas N Greve and Fran Grodstein and Christopher I Wright and Deborah Blacker and H Diana Rosas and Reisa A Sperling and Alireza Atri and John H Growdon and Bradley T Hyman and John C Morris and Bruce Fischl and Randy L Buckner},
doi = {10.1093/cercor/bhn113},
issn = {1460-2199},
year = {2009},
date = {2009-03-01},
journal = {Cereb Cortex},
volume = {19},
number = {3},
pages = {497--510},
abstract = {Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This "disease signature" approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This "disease signature" approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases.
Salat, David H; Greve, Douglas N; Pacheco, Jennifer L; Quinn, Brian T; Helmer, Karl G; Buckner, Randy L; Fischl, Bruce
Regional white matter volume differences in nondemented aging and Alzheimer's disease Journal Article
In: Neuroimage, vol. 44, no. 4, pp. 1247–1258, 2009, ISSN: 1095-9572.
@article{pmid19027860,
title = {Regional white matter volume differences in nondemented aging and Alzheimer's disease},
author = {David H Salat and Douglas N Greve and Jennifer L Pacheco and Brian T Quinn and Karl G Helmer and Randy L Buckner and Bruce Fischl},
doi = {10.1016/j.neuroimage.2008.10.030},
issn = {1095-9572},
year = {2009},
date = {2009-02-01},
journal = {Neuroimage},
volume = {44},
number = {4},
pages = {1247--1258},
abstract = {Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer's disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD associated volume loss that may contribute to cognitive decline.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer's disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD associated volume loss that may contribute to cognitive decline.
2008
Rosas, H Diana; Salat, David H; Lee, Stephanie Y; Zaleta, Alexandra K; Hevelone, Nathanael; Hersch, Steven M
Complexity and heterogeneity: what drives the ever-changing brain in Huntington's disease? Journal Article
In: Ann N Y Acad Sci, vol. 1147, pp. 196–205, 2008, ISSN: 1749-6632.
@article{pmid19076442,
title = {Complexity and heterogeneity: what drives the ever-changing brain in Huntington's disease?},
author = {H Diana Rosas and David H Salat and Stephanie Y Lee and Alexandra K Zaleta and Nathanael Hevelone and Steven M Hersch},
doi = {10.1196/annals.1427.034},
issn = {1749-6632},
year = {2008},
date = {2008-12-01},
journal = {Ann N Y Acad Sci},
volume = {1147},
pages = {196--205},
abstract = {Significant advances are being made in our understanding of basic pathophyiological and biochemical mechanisms that cause Huntington's disease (HD). There is increasing reason to believe that pathologic alterations occur in the brain for years before symptoms manifest. The "classic" hallmark of neuropathology in HD is selective neurodegeneration in which vulnerable populations of neurons degenerate while less vulnerable populations are spared. While the earliest and most striking neuropathologic changes have been found in the neostriatum, neuronal loss has been identified in many other regions of the brain. We report topologically selective, early, and progressive changes in the cortex, striatum, extrastriatal brain structures, and white matter throughout the spectrum of disease. Our growing understanding of HD underscores the reality that points to the complexity of HD. A single, well-defined, genetic mutation causes a cascade of events whose final result is an aggregate insult of the homeostatic process. We explore possible explanations for the selective vulnerability of the brain in HD. The ultimate goal in HD is to develop disease-modifying therapies that will prevent the onset of clinical symptoms in those individuals who are at risk and slow the progression of symptoms in those individuals already affected with symptoms. Understanding changes in brain morphometry and their relationship to clinical symptoms may provide important and new insights into basic pathophysiological mechanisms at play in the disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Significant advances are being made in our understanding of basic pathophyiological and biochemical mechanisms that cause Huntington's disease (HD). There is increasing reason to believe that pathologic alterations occur in the brain for years before symptoms manifest. The "classic" hallmark of neuropathology in HD is selective neurodegeneration in which vulnerable populations of neurons degenerate while less vulnerable populations are spared. While the earliest and most striking neuropathologic changes have been found in the neostriatum, neuronal loss has been identified in many other regions of the brain. We report topologically selective, early, and progressive changes in the cortex, striatum, extrastriatal brain structures, and white matter throughout the spectrum of disease. Our growing understanding of HD underscores the reality that points to the complexity of HD. A single, well-defined, genetic mutation causes a cascade of events whose final result is an aggregate insult of the homeostatic process. We explore possible explanations for the selective vulnerability of the brain in HD. The ultimate goal in HD is to develop disease-modifying therapies that will prevent the onset of clinical symptoms in those individuals who are at risk and slow the progression of symptoms in those individuals already affected with symptoms. Understanding changes in brain morphometry and their relationship to clinical symptoms may provide important and new insights into basic pathophysiological mechanisms at play in the disease.
van der Kouwe, André J W; Benner, Thomas; Salat, David H; Fischl, Bruce
Brain morphometry with multiecho MPRAGE Journal Article
In: Neuroimage, vol. 40, no. 2, pp. 559–569, 2008, ISSN: 1053-8119.
@article{pmid18242102,
title = {Brain morphometry with multiecho MPRAGE},
author = {André J W van der Kouwe and Thomas Benner and David H Salat and Bruce Fischl},
doi = {10.1016/j.neuroimage.2007.12.025},
issn = {1053-8119},
year = {2008},
date = {2008-04-01},
journal = {Neuroimage},
volume = {40},
number = {2},
pages = {559--569},
abstract = {In brain morphometry studies using magnetic resonance imaging, several scans with a range of contrasts are often collected. The images may be locally distorted due to imperfect shimming in regions where magnetic susceptibility changes rapidly, and all scans may not be distorted in the same way. In multispectral studies it is critical that the edges of structures align precisely across all contrasts. The MPRAGE (MPR) sequence has excellent contrast properties for cortical segmentation, while multiecho FLASH (MEF) provides better contrast for segmentation of subcortical structures. Here, a multiecho version of the MPRAGE (MEMPR) is evaluated using SIENA and FreeSurfer. The higher bandwidth of the MEMPR results in reduced distortions that match those of the MEF while the SNR is recovered by combining the echoes. Accurate automatic identification of cortex and thickness estimation is frustrated by the presence of dura adjacent to regions such as the entorhinal cortex. In the typical MPRAGE protocol, dura and cortex are approximately isointense. However, dura has substantially smaller T2* than cortex. This information is represented in the multiple echoes of the MEMPR. An algorithm is described for correcting cortical thickness using T2*. It is shown that with MEMPR, SIENA generates more reliable percentage brain volume changes and FreeSurfer generates more reliable cortical models. The regions where cortical thickness is affected by dura are shown. MEMPR did not substantially improve subcortical segmentations. Since acquisition time is the same for MEMPR as for MPRAGE, and it has better distortion properties and additional T2* information, MEMPR is recommended for morphometry studies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In brain morphometry studies using magnetic resonance imaging, several scans with a range of contrasts are often collected. The images may be locally distorted due to imperfect shimming in regions where magnetic susceptibility changes rapidly, and all scans may not be distorted in the same way. In multispectral studies it is critical that the edges of structures align precisely across all contrasts. The MPRAGE (MPR) sequence has excellent contrast properties for cortical segmentation, while multiecho FLASH (MEF) provides better contrast for segmentation of subcortical structures. Here, a multiecho version of the MPRAGE (MEMPR) is evaluated using SIENA and FreeSurfer. The higher bandwidth of the MEMPR results in reduced distortions that match those of the MEF while the SNR is recovered by combining the echoes. Accurate automatic identification of cortex and thickness estimation is frustrated by the presence of dura adjacent to regions such as the entorhinal cortex. In the typical MPRAGE protocol, dura and cortex are approximately isointense. However, dura has substantially smaller T2* than cortex. This information is represented in the multiple echoes of the MEMPR. An algorithm is described for correcting cortical thickness using T2*. It is shown that with MEMPR, SIENA generates more reliable percentage brain volume changes and FreeSurfer generates more reliable cortical models. The regions where cortical thickness is affected by dura are shown. MEMPR did not substantially improve subcortical segmentations. Since acquisition time is the same for MEMPR as for MPRAGE, and it has better distortion properties and additional T2* information, MEMPR is recommended for morphometry studies.
Rosas, H Diana; Salat, David H; Lee, Stephanie Y; Zaleta, Alexandra K; Pappu, Vasanth; Fischl, Bruce; Greve, Doug; Hevelone, Nathanael; Hersch, Steven M
Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity Journal Article
In: Brain, vol. 131, no. Pt 4, pp. 1057–1068, 2008, ISSN: 1460-2156.
@article{pmid18337273,
title = {Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity},
author = {H Diana Rosas and David H Salat and Stephanie Y Lee and Alexandra K Zaleta and Vasanth Pappu and Bruce Fischl and Doug Greve and Nathanael Hevelone and Steven M Hersch},
doi = {10.1093/brain/awn025},
issn = {1460-2156},
year = {2008},
date = {2008-04-01},
journal = {Brain},
volume = {131},
number = {Pt 4},
pages = {1057--1068},
abstract = {The clinical phenotype of Huntington's disease (HD) is far more complex and variable than depictions of it as a progressive movement disorder dominated by neostriatal pathology represent. The availability of novel neuro-imaging methods has enabled us to evaluate cerebral cortical changes in HD, which we have found to occur early and to be topographically selective. What is less clear, however, is how these changes influence the clinical expression of the disease. In this study, we used a high-resolution surface based analysis of in vivo MRI data to measure cortical thickness in 33 individuals with HD, spanning the spectrum of disease and 22 age- and sex-matched controls. We found close relationships between specific functional and cognitive measures and topologically specific cortical regions. We also found that distinct motor phenotypes were associated with discrete patterns of cortical thinning. The selective topographical associations of cortical thinning with clinical features of HD suggest that we are not simply correlating global worsening with global cortical degeneration. Our results indicate that cortical involvement contributes to important symptoms, including those that have been ascribed primarily to the striatum, and that topologically selective changes in the cortex might explain much of the clinical heterogeneity found in HD. Additionally, a significant association between regional cortical thinning and total functional capacity, currently the leading primary outcome measure used in neuroprotection trials for HD, establishes cortical MRI morphometry as a potential biomarker of disease progression.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The clinical phenotype of Huntington's disease (HD) is far more complex and variable than depictions of it as a progressive movement disorder dominated by neostriatal pathology represent. The availability of novel neuro-imaging methods has enabled us to evaluate cerebral cortical changes in HD, which we have found to occur early and to be topographically selective. What is less clear, however, is how these changes influence the clinical expression of the disease. In this study, we used a high-resolution surface based analysis of in vivo MRI data to measure cortical thickness in 33 individuals with HD, spanning the spectrum of disease and 22 age- and sex-matched controls. We found close relationships between specific functional and cognitive measures and topologically specific cortical regions. We also found that distinct motor phenotypes were associated with discrete patterns of cortical thinning. The selective topographical associations of cortical thinning with clinical features of HD suggest that we are not simply correlating global worsening with global cortical degeneration. Our results indicate that cortical involvement contributes to important symptoms, including those that have been ascribed primarily to the striatum, and that topologically selective changes in the cortex might explain much of the clinical heterogeneity found in HD. Additionally, a significant association between regional cortical thinning and total functional capacity, currently the leading primary outcome measure used in neuroprotection trials for HD, establishes cortical MRI morphometry as a potential biomarker of disease progression.
2007
Johnson, Keith A; Gregas, Matt; Becker, John A; Kinnecom, Catherine; Salat, David H; Moran, Erin K; Smith, Erin E; Rosand, Jonathan; Rentz, Dorene M; Klunk, William E; Mathis, Chester A; Price, Julie C; Dekosky, Steven T; Fischman, Alan J; Greenberg, Steven M
Imaging of amyloid burden and distribution in cerebral amyloid angiopathy Journal Article
In: Ann Neurol, vol. 62, no. 3, pp. 229–234, 2007, ISSN: 0364-5134.
@article{pmid17683091,
title = {Imaging of amyloid burden and distribution in cerebral amyloid angiopathy},
author = {Keith A Johnson and Matt Gregas and John A Becker and Catherine Kinnecom and David H Salat and Erin K Moran and Erin E Smith and Jonathan Rosand and Dorene M Rentz and William E Klunk and Chester A Mathis and Julie C Price and Steven T Dekosky and Alan J Fischman and Steven M Greenberg},
doi = {10.1002/ana.21164},
issn = {0364-5134},
year = {2007},
date = {2007-09-01},
journal = {Ann Neurol},
volume = {62},
number = {3},
pages = {229--234},
abstract = {OBJECTIVE: Cerebrovascular deposition of beta-amyloid (cerebral amyloid angiopathy [CAA]) is a major cause of hemorrhagic stroke and a likely contributor to vascular cognitive impairment. We evaluated positron emission tomographic imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB) as a potential noninvasive method for detection of CAA. We hypothesized that amyloid deposition would be observed with PiB in CAA, and based on the occipital predilection of CAA pathology and associated hemorrhages, that specific PiB retention would be disproportionately greater in occipital lobes.nnMETHODS: We compared specific cortical PiB retention in 6 nondemented subjects diagnosed with probable CAA with 15 healthy control subjects and 9 patients with probable Alzheimer's disease (AD).nnRESULTS: All CAA and AD subjects were PiB-positive, both by distribution volume ratio measurements and by visual inspection of positron emission tomographic images. Global cortical PiB retention was significantly increased in CAA (distribution volume ratio 1.18 +/- 0.06) relative to healthy control subjects (1.04 +/- 0.10; p = 0.0009), but was lower in CAA than in AD subjects (1.41 +/- 0.17; p = 0.002). The occipital-to-global PiB ratio, however, was significantly greater in CAA than in AD subjects (0.99 +/- 0.07 vs 0.86 +/- 0.05; p = 0.003).nnINTERPRETATION: We conclude that PiB-positron emission tomography can detect cerebrovascular beta-amyloid and may serve as a method for identifying the extent of CAA in living subjects.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Cerebrovascular deposition of beta-amyloid (cerebral amyloid angiopathy [CAA]) is a major cause of hemorrhagic stroke and a likely contributor to vascular cognitive impairment. We evaluated positron emission tomographic imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB) as a potential noninvasive method for detection of CAA. We hypothesized that amyloid deposition would be observed with PiB in CAA, and based on the occipital predilection of CAA pathology and associated hemorrhages, that specific PiB retention would be disproportionately greater in occipital lobes.nnMETHODS: We compared specific cortical PiB retention in 6 nondemented subjects diagnosed with probable CAA with 15 healthy control subjects and 9 patients with probable Alzheimer's disease (AD).nnRESULTS: All CAA and AD subjects were PiB-positive, both by distribution volume ratio measurements and by visual inspection of positron emission tomographic images. Global cortical PiB retention was significantly increased in CAA (distribution volume ratio 1.18 +/- 0.06) relative to healthy control subjects (1.04 +/- 0.10; p = 0.0009), but was lower in CAA than in AD subjects (1.41 +/- 0.17; p = 0.002). The occipital-to-global PiB ratio, however, was significantly greater in CAA than in AD subjects (0.99 +/- 0.07 vs 0.86 +/- 0.05; p = 0.003).nnINTERPRETATION: We conclude that PiB-positron emission tomography can detect cerebrovascular beta-amyloid and may serve as a method for identifying the extent of CAA in living subjects.
2006
Rosas, H Diana; Tuch, David S; Hevelone, Nathanael D; Zaleta, Alexandra K; Vangel, Mark; Hersch, Steven M; Salat, David H
In: Mov Disord, vol. 21, no. 9, pp. 1317–1325, 2006, ISSN: 0885-3185.
@article{pmid16755582,
title = {Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures},
author = {H Diana Rosas and David S Tuch and Nathanael D Hevelone and Alexandra K Zaleta and Mark Vangel and Steven M Hersch and David H Salat},
doi = {10.1002/mds.20979},
issn = {0885-3185},
year = {2006},
date = {2006-09-01},
journal = {Mov Disord},
volume = {21},
number = {9},
pages = {1317--1325},
abstract = {Atrophy of cortical and subcortical gray matter is apparent in Huntington's disease (HD) before symptoms manifest. We hypothesized that the white matter (WM) connecting cortical and subcortical regions must also be affected early and that select clinical symptoms were related to systems degeneration. We used diffusion tensor magnetic resonance imaging (DTI) to examine the regional nature of WM abnormalities in early HD, including the preclinical period, and to determine whether regional changes correlated with clinical features. We studied individuals in early stages (HD), presymptomatic individuals known to carry the genetic mutation that causes HD (Pre-HD), and matched healthy controls. DTI indices of tissue integrity were obtained from several regions of interest, including the corpus callosum (CC), internal capsule (IC), and basal ganglia, were compared across groups by t tests, and were correlated to cognitive and clinical measures. WM alterations were found throughout the CC, in the anterior and posterior limbs of the IC, and in frontal subcortical WM in HD subjects, supporting the selective involvement of the pyramidal tracts in HD; a similar distribution of changes was seen in Pre-HD subjects, supporting presymptomatic alterations. There was a significant relationship between select DTI measures and cognitive performance. Alterations in diffusion indices were also seen in the striatum that were independent of atrophy. Our findings support that WM alterations occur very early in HD. The distribution of the changes suggests that these changes contribute to the disruption of pyramidal and extrapyramidal circuits and also support a role of compromised cortical circuitry in early cognitive and subtle motor impairment during the preclinical stages of HD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Atrophy of cortical and subcortical gray matter is apparent in Huntington's disease (HD) before symptoms manifest. We hypothesized that the white matter (WM) connecting cortical and subcortical regions must also be affected early and that select clinical symptoms were related to systems degeneration. We used diffusion tensor magnetic resonance imaging (DTI) to examine the regional nature of WM abnormalities in early HD, including the preclinical period, and to determine whether regional changes correlated with clinical features. We studied individuals in early stages (HD), presymptomatic individuals known to carry the genetic mutation that causes HD (Pre-HD), and matched healthy controls. DTI indices of tissue integrity were obtained from several regions of interest, including the corpus callosum (CC), internal capsule (IC), and basal ganglia, were compared across groups by t tests, and were correlated to cognitive and clinical measures. WM alterations were found throughout the CC, in the anterior and posterior limbs of the IC, and in frontal subcortical WM in HD subjects, supporting the selective involvement of the pyramidal tracts in HD; a similar distribution of changes was seen in Pre-HD subjects, supporting presymptomatic alterations. There was a significant relationship between select DTI measures and cognitive performance. Alterations in diffusion indices were also seen in the striatum that were independent of atrophy. Our findings support that WM alterations occur very early in HD. The distribution of the changes suggests that these changes contribute to the disruption of pyramidal and extrapyramidal circuits and also support a role of compromised cortical circuitry in early cognitive and subtle motor impairment during the preclinical stages of HD.
Salat, David H; Smith, Eric E; Tuch, David S; Benner, Thomas; Pappu, Vasanth; Schwab, Kristin M; Gurol, M Edip; Rosas, H Diana; Rosand, Jonathan; Greenberg, Steven M
White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging Journal Article
In: Stroke, vol. 37, no. 7, pp. 1759–1764, 2006, ISSN: 1524-4628.
@article{pmid16763176,
title = {White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging},
author = {David H Salat and Eric E Smith and David S Tuch and Thomas Benner and Vasanth Pappu and Kristin M Schwab and M Edip Gurol and H Diana Rosas and Jonathan Rosand and Steven M Greenberg},
doi = {10.1161/01.STR.0000227328.86353.a7},
issn = {1524-4628},
year = {2006},
date = {2006-07-01},
journal = {Stroke},
volume = {37},
number = {7},
pages = {1759--1764},
abstract = {BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) represents beta-amyloid deposition in the small- and medium-sized vessels of the brain and meninges. CAA contributes to altered vessel function and is associated with white matter damage, cognitive impairment, and most salient, hemorrhagic stroke. We used diffusion tensor imaging to evaluate the anatomic distribution of white matter degeneration in participants diagnosed with advanced CAA.nnMETHODS: Diffusion tensor imaging was obtained from 11 participants diagnosed with CAA-related intracerebral hemorrhage and 13 matched healthy control participants. Fractional anisotropy (FA) and diffusivity maps were compared using voxel based t test and region-of-interest analyses.nnRESULTS: FA was reduced in CAA in temporal white matter and in the splenium of the corpus callosum (P<0.001 with approximately 17% reduction in temporal white matter and 15% reduction in the splenium). FA was marginally increased in CAA in the posterior limb of the internal capsule and subthalamic gray matter regions (approximately 7% increase in subthalamic gray). FA changes were bilateral, remained significant in cluster analysis controlling for multiple comparisons, and did not depend on the hemisphere of the cerebral hemorrhage. Diffusivity was not substantially altered.nnCONCLUSIONS: These findings suggest that a pattern of regional brain tissue degeneration is a characteristic feature of advanced CAA.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) represents beta-amyloid deposition in the small- and medium-sized vessels of the brain and meninges. CAA contributes to altered vessel function and is associated with white matter damage, cognitive impairment, and most salient, hemorrhagic stroke. We used diffusion tensor imaging to evaluate the anatomic distribution of white matter degeneration in participants diagnosed with advanced CAA.nnMETHODS: Diffusion tensor imaging was obtained from 11 participants diagnosed with CAA-related intracerebral hemorrhage and 13 matched healthy control participants. Fractional anisotropy (FA) and diffusivity maps were compared using voxel based t test and region-of-interest analyses.nnRESULTS: FA was reduced in CAA in temporal white matter and in the splenium of the corpus callosum (P<0.001 with approximately 17% reduction in temporal white matter and 15% reduction in the splenium). FA was marginally increased in CAA in the posterior limb of the internal capsule and subthalamic gray matter regions (approximately 7% increase in subthalamic gray). FA changes were bilateral, remained significant in cluster analysis controlling for multiple comparisons, and did not depend on the hemisphere of the cerebral hemorrhage. Diffusivity was not substantially altered.nnCONCLUSIONS: These findings suggest that a pattern of regional brain tissue degeneration is a characteristic feature of advanced CAA.
2005
Tuch, David S; Salat, David H; Wisco, Jonathan J; Zaleta, Alexandra K; Hevelone, Nathanael D; Rosas, H Diana
Choice reaction time performance correlates with diffusion anisotropy in white matter pathways supporting visuospatial attention Journal Article
In: Proc Natl Acad Sci U S A, vol. 102, no. 34, pp. 12212–12217, 2005, ISSN: 0027-8424.
@article{pmid16103359,
title = {Choice reaction time performance correlates with diffusion anisotropy in white matter pathways supporting visuospatial attention},
author = {David S Tuch and David H Salat and Jonathan J Wisco and Alexandra K Zaleta and Nathanael D Hevelone and H Diana Rosas},
doi = {10.1073/pnas.0407259102},
issn = {0027-8424},
year = {2005},
date = {2005-08-01},
journal = {Proc Natl Acad Sci U S A},
volume = {102},
number = {34},
pages = {12212--12217},
abstract = {Humans exhibit significant interindividual variability in behavioral reaction time (RT) performance yet the underlying neural mechanisms for this variability remain largely unknown. It has been proposed that interindividual variability in RT performance may be due to differences in white matter (WM) physiological properties, although such a relationship has never been demonstrated in cortical projection or association pathways in healthy young adults. Using diffusion tensor MRI (DTI), we sought to test whether diffusion tensor fractional anisotropy (FA), a measure of the orientational coherence of water self-diffusion, is regionally correlated with RT on a visual self-paced choice RT (CRT) task. CRT was found to be significantly correlated with FA in projection and association pathways supporting visuospatial attention including the right optic radiation, right posterior thalamus, and right medial precuneus WM. Significant correlations were also observed in left superior temporal sulcus WM and the left parietal operculum. The lateralization of the CRT-FA correlation to right visual and parietal WM pathways is consistent with the specialization of right visual and parietal cortices for visuospatial attention. The localization of the CRT-FA correlations to predominantly visual and parietal WM pathways, but not to motor pathways or the corpus callosum indicates that individual differences in visual CRT performance are associated with variations in the WM underlying the visuospatial attention network as opposed to pathways supporting motor movement or interhemispheric transmission.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Humans exhibit significant interindividual variability in behavioral reaction time (RT) performance yet the underlying neural mechanisms for this variability remain largely unknown. It has been proposed that interindividual variability in RT performance may be due to differences in white matter (WM) physiological properties, although such a relationship has never been demonstrated in cortical projection or association pathways in healthy young adults. Using diffusion tensor MRI (DTI), we sought to test whether diffusion tensor fractional anisotropy (FA), a measure of the orientational coherence of water self-diffusion, is regionally correlated with RT on a visual self-paced choice RT (CRT) task. CRT was found to be significantly correlated with FA in projection and association pathways supporting visuospatial attention including the right optic radiation, right posterior thalamus, and right medial precuneus WM. Significant correlations were also observed in left superior temporal sulcus WM and the left parietal operculum. The lateralization of the CRT-FA correlation to right visual and parietal WM pathways is consistent with the specialization of right visual and parietal cortices for visuospatial attention. The localization of the CRT-FA correlations to predominantly visual and parietal WM pathways, but not to motor pathways or the corpus callosum indicates that individual differences in visual CRT performance are associated with variations in the WM underlying the visuospatial attention network as opposed to pathways supporting motor movement or interhemispheric transmission.
van der Kouwe, André J W; Benner, Thomas; Fischl, Bruce; Schmitt, Franz; Salat, David H; Harder, Martin; Sorensen, A Gregory; Dale, Anders M
On-line automatic slice positioning for brain MR imaging Journal Article
In: Neuroimage, vol. 27, no. 1, pp. 222–230, 2005, ISSN: 1053-8119.
@article{pmid15886023,
title = {On-line automatic slice positioning for brain MR imaging},
author = {André J W van der Kouwe and Thomas Benner and Bruce Fischl and Franz Schmitt and David H Salat and Martin Harder and A Gregory Sorensen and Anders M Dale},
doi = {10.1016/j.neuroimage.2005.03.035},
issn = {1053-8119},
year = {2005},
date = {2005-08-01},
journal = {Neuroimage},
volume = {27},
number = {1},
pages = {222--230},
abstract = {In clinical brain MR imaging protocols, the technician collects a quick localizer and manually positions the subsequent scans using the localizer as a guide. We present a method for automatic slice positioning using a rapidly acquired 3D localizer. The localizer is automatically aligned to a statistical atlas representing 40 healthy subjects. The atlas contains the probability of a given tissue type occurring at a given location in atlas space and the conditional probability distribution of the multi-spectral MRI intensity values for a given tissue class. Accurate rigid alignment of each subject to an atlas ensures that all patients' scans are acquired in a consistent manner. A further benefit is that slices are positioned consistently over time, so that scans of patients returning for follow-up imaging can be compared side-by-side to accurately monitor the progression of illness. The procedure also helps ensure that left/right asymmetries reflect true anatomy rather than being the result of oblique slice positioning relative to the underlying anatomy. The use of an atlas-based procedure eliminates the need to refer to a database of previously scanned images of the same patient and ensures corresponding alignment across scanners and sites, without requiring fiducial markers. Since the registration method is probabilistic, the registration error tends to increase smoothly in the presence of increasing noise and unusual anatomy or pathology rather than failing catastrophically. Translations and rotations relative to the atlas can be set so that planning can be done in anatomical space, rather than scanner coordinates, and stored as part of the protocol allowing standardization of slice orientations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In clinical brain MR imaging protocols, the technician collects a quick localizer and manually positions the subsequent scans using the localizer as a guide. We present a method for automatic slice positioning using a rapidly acquired 3D localizer. The localizer is automatically aligned to a statistical atlas representing 40 healthy subjects. The atlas contains the probability of a given tissue type occurring at a given location in atlas space and the conditional probability distribution of the multi-spectral MRI intensity values for a given tissue class. Accurate rigid alignment of each subject to an atlas ensures that all patients' scans are acquired in a consistent manner. A further benefit is that slices are positioned consistently over time, so that scans of patients returning for follow-up imaging can be compared side-by-side to accurately monitor the progression of illness. The procedure also helps ensure that left/right asymmetries reflect true anatomy rather than being the result of oblique slice positioning relative to the underlying anatomy. The use of an atlas-based procedure eliminates the need to refer to a database of previously scanned images of the same patient and ensures corresponding alignment across scanners and sites, without requiring fiducial markers. Since the registration method is probabilistic, the registration error tends to increase smoothly in the presence of increasing noise and unusual anatomy or pathology rather than failing catastrophically. Translations and rotations relative to the atlas can be set so that planning can be done in anatomical space, rather than scanner coordinates, and stored as part of the protocol allowing standardization of slice orientations.
Augustinack, Jean C; van der Kouwe, Andre J W; Blackwell, Megan L; Salat, David H; Wiggins, Christopher J; Frosch, Matthew P; Wiggins, Graham C; Potthast, Andreas; Wald, Lawrence L; Fischl, Bruce R
Detection of entorhinal layer II using 7Tesla [corrected] magnetic resonance imaging Journal Article
In: Ann Neurol, vol. 57, no. 4, pp. 489–494, 2005, ISSN: 0364-5134.
@article{pmid15786476,
title = {Detection of entorhinal layer II using 7Tesla [corrected] magnetic resonance imaging},
author = {Jean C Augustinack and Andre J W van der Kouwe and Megan L Blackwell and David H Salat and Christopher J Wiggins and Matthew P Frosch and Graham C Wiggins and Andreas Potthast and Lawrence L Wald and Bruce R Fischl},
doi = {10.1002/ana.20426},
issn = {0364-5134},
year = {2005},
date = {2005-04-01},
journal = {Ann Neurol},
volume = {57},
number = {4},
pages = {489--494},
abstract = {The entorhinal cortex lies in the mediotemporal lobe and has major functional, structural, and clinical significance. The entorhinal cortex has a unique cytoarchitecture with large stellate neurons in layer II that form clusters. The entorhinal cortex receives vast sensory association input, and its major output arises from the layer II and III neurons that form the perforant pathway. Clinically, the neurons in layer II are affected with neurofibrillary tangles, one of the two pathological hallmarks of Alzheimer's disease. We describe detection of the entorhinal layer II islands using magnetic resonance imaging. We scanned human autopsied temporal lobe blocks in a 7T human scanner using a solenoid coil. In 70 and 100 microm isotropic data, the entorhinal islands were clearly visible throughout the anterior-posterior extent of entorhinal cortex. Layer II islands were prominent in both the magnetic resonance imaging and corresponding histological sections, showing similar size and shape in two types of data. Area borders and island location based on cytoarchitectural features in the mediotemporal lobe were robustly detected using the magnetic resonance images. Our ex vivo results could break ground for high-resolution in vivo scanning that could ultimately benefit early diagnosis and treatment of neurodegenerative disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The entorhinal cortex lies in the mediotemporal lobe and has major functional, structural, and clinical significance. The entorhinal cortex has a unique cytoarchitecture with large stellate neurons in layer II that form clusters. The entorhinal cortex receives vast sensory association input, and its major output arises from the layer II and III neurons that form the perforant pathway. Clinically, the neurons in layer II are affected with neurofibrillary tangles, one of the two pathological hallmarks of Alzheimer's disease. We describe detection of the entorhinal layer II islands using magnetic resonance imaging. We scanned human autopsied temporal lobe blocks in a 7T human scanner using a solenoid coil. In 70 and 100 microm isotropic data, the entorhinal islands were clearly visible throughout the anterior-posterior extent of entorhinal cortex. Layer II islands were prominent in both the magnetic resonance imaging and corresponding histological sections, showing similar size and shape in two types of data. Area borders and island location based on cytoarchitectural features in the mediotemporal lobe were robustly detected using the magnetic resonance images. Our ex vivo results could break ground for high-resolution in vivo scanning that could ultimately benefit early diagnosis and treatment of neurodegenerative disease.
Gold, Brian T; Balota, Dave A; Cortese, Michael J; Sergent-Marshall, Susan D; Snyder, Abraham Z; Salat, David H; Fischl, Bruce; Dale, Anders M; Morris, John C; Buckner, Randy L
In: Neuropsychologia, vol. 43, no. 6, pp. 833–846, 2005, ISSN: 0028-3932.
@article{pmid15716156,
title = {Differing neuropsychological and neuroanatomical correlates of abnormal reading in early-stage semantic dementia and dementia of the Alzheimer type},
author = {Brian T Gold and Dave A Balota and Michael J Cortese and Susan D Sergent-Marshall and Abraham Z Snyder and David H Salat and Bruce Fischl and Anders M Dale and John C Morris and Randy L Buckner},
doi = {10.1016/j.neuropsychologia.2004.10.005},
issn = {0028-3932},
year = {2005},
date = {2005-01-01},
journal = {Neuropsychologia},
volume = {43},
number = {6},
pages = {833--846},
abstract = {Individuals with semantic dementia (SD) were differentiated neuropsychologically from individuals with dementia of the Alzheimer type (DAT) at very mild-to-mild stages (clinical dementia rating 0.5 or 1). A picture naming and recognition memory experiment provided a particularly useful probe for early identification, with SD individuals showing preserved picture recognition memory and impaired naming, and DAT individuals tending to show the reverse dissociation. The identification of an early SD group provided the opportunity to inform models of reading by exploring the influence of isolated lexical semantic impairment on reading regular words. Results demonstrated prolonged latency in both SD and DAT group reading compared to a control group but exaggerated influence of frequency and length only for the SD group. The SD reading pattern was associated with focal atrophy of the left temporal pole. These cognitive-neuroanatomical findings suggest a role for the left temporal pole in lexical/semantic components of reading and demonstrate that cortical thickness differences in the left temporal pole correlate with prolonged latency associated with increased reliance on sublexical components of reading.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Individuals with semantic dementia (SD) were differentiated neuropsychologically from individuals with dementia of the Alzheimer type (DAT) at very mild-to-mild stages (clinical dementia rating 0.5 or 1). A picture naming and recognition memory experiment provided a particularly useful probe for early identification, with SD individuals showing preserved picture recognition memory and impaired naming, and DAT individuals tending to show the reverse dissociation. The identification of an early SD group provided the opportunity to inform models of reading by exploring the influence of isolated lexical semantic impairment on reading regular words. Results demonstrated prolonged latency in both SD and DAT group reading compared to a control group but exaggerated influence of frequency and length only for the SD group. The SD reading pattern was associated with focal atrophy of the left temporal pole. These cognitive-neuroanatomical findings suggest a role for the left temporal pole in lexical/semantic components of reading and demonstrate that cortical thickness differences in the left temporal pole correlate with prolonged latency associated with increased reliance on sublexical components of reading.
2004
Dickerson, Bradford C; Salat, David H; Bates, Julianna F; Atiya, Monika; Killiany, Ronald J; Greve, Douglas N; Dale, Anders M; Stern, Chantal E; Blacker, Deborah; Albert, Marilyn S; Sperling, Reisa A
Medial temporal lobe function and structure in mild cognitive impairment Journal Article
In: Ann Neurol, vol. 56, no. 1, pp. 27–35, 2004, ISSN: 0364-5134.
@article{pmid15236399,
title = {Medial temporal lobe function and structure in mild cognitive impairment},
author = {Bradford C Dickerson and David H Salat and Julianna F Bates and Monika Atiya and Ronald J Killiany and Douglas N Greve and Anders M Dale and Chantal E Stern and Deborah Blacker and Marilyn S Albert and Reisa A Sperling},
doi = {10.1002/ana.20163},
issn = {0364-5134},
year = {2004},
date = {2004-07-01},
journal = {Ann Neurol},
volume = {56},
number = {1},
pages = {27--35},
abstract = {Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline.
Salat, David H; Buckner, Randy L; Snyder, Abraham Z; Greve, Douglas N; Desikan, Rahul S R; Busa, Evelina; Morris, John C; Dale, Anders M; Fischl, Bruce
Thinning of the cerebral cortex in aging Journal Article
In: Cereb Cortex, vol. 14, no. 7, pp. 721–730, 2004, ISSN: 1047-3211.
@article{pmid15054051,
title = {Thinning of the cerebral cortex in aging},
author = {David H Salat and Randy L Buckner and Abraham Z Snyder and Douglas N Greve and Rahul S R Desikan and Evelina Busa and John C Morris and Anders M Dale and Bruce Fischl},
doi = {10.1093/cercor/bhh032},
issn = {1047-3211},
year = {2004},
date = {2004-07-01},
journal = {Cereb Cortex},
volume = {14},
number = {7},
pages = {721--730},
abstract = {The thickness of the cerebral cortex was measured in 106 non-demented participants ranging in age from 18 to 93 years. For each participant, multiple acquisitions of structural T1-weighted magnetic resonance imaging (MRI) scans were averaged to yield high-resolution, high-contrast data sets. Cortical thickness was estimated as the distance between the gray/white boundary and the outer cortical surface, resulting in a continuous estimate across the cortical mantle. Global thinning was apparent by middle age. Men and women showed a similar degree of global thinning, and did not differ in mean thickness in the younger or older groups. Age-associated differences were widespread but demonstrated a patchwork of regional atrophy and sparing. Examination of subsets of the data from independent samples produced highly similar age-associated patterns of atrophy, suggesting that the specific anatomic patterns within the maps were reliable. Certain results, including prominent atrophy of prefrontal cortex and relative sparing of temporal and parahippocampal cortex, converged with previous findings. Other results were unexpected, such as the finding of prominent atrophy in frontal cortex near primary motor cortex and calcarine cortex near primary visual cortex. These findings demonstrate that cortical thinning occurs by middle age and spans widespread cortical regions that include primary as well as association cortex.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The thickness of the cerebral cortex was measured in 106 non-demented participants ranging in age from 18 to 93 years. For each participant, multiple acquisitions of structural T1-weighted magnetic resonance imaging (MRI) scans were averaged to yield high-resolution, high-contrast data sets. Cortical thickness was estimated as the distance between the gray/white boundary and the outer cortical surface, resulting in a continuous estimate across the cortical mantle. Global thinning was apparent by middle age. Men and women showed a similar degree of global thinning, and did not differ in mean thickness in the younger or older groups. Age-associated differences were widespread but demonstrated a patchwork of regional atrophy and sparing. Examination of subsets of the data from independent samples produced highly similar age-associated patterns of atrophy, suggesting that the specific anatomic patterns within the maps were reliable. Certain results, including prominent atrophy of prefrontal cortex and relative sparing of temporal and parahippocampal cortex, converged with previous findings. Other results were unexpected, such as the finding of prominent atrophy in frontal cortex near primary motor cortex and calcarine cortex near primary visual cortex. These findings demonstrate that cortical thinning occurs by middle age and spans widespread cortical regions that include primary as well as association cortex.
Fischl, Bruce; van der Kouwe, André; Destrieux, Christophe; Halgren, Eric; Ségonne, Florent; Salat, David H; Busa, Evelina; Seidman, Larry J; Goldstein, Jill; Kennedy, David; Caviness, Verne; Makris, Nikos; Rosen, Bruce; Dale, Anders M
Automatically parcellating the human cerebral cortex Journal Article
In: Cereb Cortex, vol. 14, no. 1, pp. 11–22, 2004, ISSN: 1047-3211.
@article{pmid14654453,
title = {Automatically parcellating the human cerebral cortex},
author = {Bruce Fischl and André van der Kouwe and Christophe Destrieux and Eric Halgren and Florent Ségonne and David H Salat and Evelina Busa and Larry J Seidman and Jill Goldstein and David Kennedy and Verne Caviness and Nikos Makris and Bruce Rosen and Anders M Dale},
doi = {10.1093/cercor/bhg087},
issn = {1047-3211},
year = {2004},
date = {2004-01-01},
journal = {Cereb Cortex},
volume = {14},
number = {1},
pages = {11--22},
abstract = {We present a technique for automatically assigning a neuroanatomical label to each location on a cortical surface model based on probabilistic information estimated from a manually labeled training set. This procedure incorporates both geometric information derived from the cortical model, and neuroanatomical convention, as found in the training set. The result is a complete labeling of cortical sulci and gyri. Examples are given from two different training sets generated using different neuroanatomical conventions, illustrating the flexibility of the algorithm. The technique is shown to be comparable in accuracy to manual labeling.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present a technique for automatically assigning a neuroanatomical label to each location on a cortical surface model based on probabilistic information estimated from a manually labeled training set. This procedure incorporates both geometric information derived from the cortical model, and neuroanatomical convention, as found in the training set. The result is a complete labeling of cortical sulci and gyri. Examples are given from two different training sets generated using different neuroanatomical conventions, illustrating the flexibility of the algorithm. The technique is shown to be comparable in accuracy to manual labeling.
Fischl, Bruce; Salat, David H; van der Kouwe, André J W; Makris, Nikos; Ségonne, Florent; Quinn, Brian T; Dale, Anders M
Sequence-independent segmentation of magnetic resonance images Journal Article
In: Neuroimage, vol. 23 Suppl 1, pp. S69–S84, 2004, ISSN: 1053-8119.
@article{pmid15501102,
title = {Sequence-independent segmentation of magnetic resonance images},
author = {Bruce Fischl and David H Salat and André J W van der Kouwe and Nikos Makris and Florent Ségonne and Brian T Quinn and Anders M Dale},
doi = {10.1016/j.neuroimage.2004.07.016},
issn = {1053-8119},
year = {2004},
date = {2004-01-01},
journal = {Neuroimage},
volume = {23 Suppl 1},
pages = {S69--S84},
abstract = {We present a set of techniques for embedding the physics of the imaging process that generates a class of magnetic resonance images (MRIs) into a segmentation or registration algorithm. This results in substantial invariance to acquisition parameters, as the effect of these parameters on the contrast properties of various brain structures is explicitly modeled in the segmentation. In addition, the integration of image acquisition with tissue classification allows the derivation of sequences that are optimal for segmentation purposes. Another benefit of these procedures is the generation of probabilistic models of the intrinsic tissue parameters that cause MR contrast (e.g., T1, proton density, T2*), allowing access to these physiologically relevant parameters that may change with disease or demographic, resulting in nonmorphometric alterations in MR images that are otherwise difficult to detect. Finally, we also present a high band width multiecho FLASH pulse sequence that results in high signal-to-noise ratio with minimal image distortion due to B0 effects. This sequence has the added benefit of allowing the explicit estimation of T2* and of reducing test-retest intensity variability.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present a set of techniques for embedding the physics of the imaging process that generates a class of magnetic resonance images (MRIs) into a segmentation or registration algorithm. This results in substantial invariance to acquisition parameters, as the effect of these parameters on the contrast properties of various brain structures is explicitly modeled in the segmentation. In addition, the integration of image acquisition with tissue classification allows the derivation of sequences that are optimal for segmentation purposes. Another benefit of these procedures is the generation of probabilistic models of the intrinsic tissue parameters that cause MR contrast (e.g., T1, proton density, T2*), allowing access to these physiologically relevant parameters that may change with disease or demographic, resulting in nonmorphometric alterations in MR images that are otherwise difficult to detect. Finally, we also present a high band width multiecho FLASH pulse sequence that results in high signal-to-noise ratio with minimal image distortion due to B0 effects. This sequence has the added benefit of allowing the explicit estimation of T2* and of reducing test-retest intensity variability.
2003
Kuperberg, Gina R; Broome, Matthew R; McGuire, Philip K; David, Anthony S; Eddy, Marianna; Ozawa, Fujiro; Goff, Donald; West, W Caroline; Williams, Steven C R; van der Kouwe, Andre J W; Salat, David H; Dale, Anders M; Fischl, Bruce
Regionally localized thinning of the cerebral cortex in schizophrenia Journal Article
In: Arch Gen Psychiatry, vol. 60, no. 9, pp. 878–888, 2003, ISSN: 0003-990X.
@article{pmid12963669,
title = {Regionally localized thinning of the cerebral cortex in schizophrenia},
author = {Gina R Kuperberg and Matthew R Broome and Philip K McGuire and Anthony S David and Marianna Eddy and Fujiro Ozawa and Donald Goff and W Caroline West and Steven C R Williams and Andre J W van der Kouwe and David H Salat and Anders M Dale and Bruce Fischl},
doi = {10.1001/archpsyc.60.9.878},
issn = {0003-990X},
year = {2003},
date = {2003-09-01},
journal = {Arch Gen Psychiatry},
volume = {60},
number = {9},
pages = {878--888},
abstract = {BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps.nnMETHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon.nnRESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels.nnCONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps.nnMETHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon.nnRESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels.nnCONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.
2002
Salat, David H; Kaye, Jeffrey A; Janowsky, Jeri S
Greater orbital prefrontal volume selectively predicts worse working memory performance in older adults Journal Article
In: Cereb Cortex, vol. 12, no. 5, pp. 494–505, 2002, ISSN: 1047-3211.
@article{pmid11950767,
title = {Greater orbital prefrontal volume selectively predicts worse working memory performance in older adults},
author = {David H Salat and Jeffrey A Kaye and Jeri S Janowsky},
doi = {10.1093/cercor/12.5.494},
issn = {1047-3211},
year = {2002},
date = {2002-05-01},
journal = {Cereb Cortex},
volume = {12},
number = {5},
pages = {494--505},
abstract = {Alterations of the prefrontal cortex (PFC) could contribute to cognitive decline in older adults. We examined the specificity of age-related PFC degeneration and whether cognitive abilities were related to volumetric measurements. Older and younger subjects were tested using a battery of tasks supported by different subregions within the PFC. The cognitive data from older subjects were related to PFC volumetric measurements in order to determine whether cortical morphology was predictive of individual differences in task performance within this age range (72-94 years). Working memory performance best distinguished older from younger subjects. Working memory measures but not other measures were correlated with age in both groups. A larger orbital PFC volume was related to a worse working memory performance and a larger superior PFC volume was related to worse conditional association learning. The volumes of these regions were not related to performance on other tasks. These results suggest that working memory is a sensitive measure of cognitive aging and that regional morphology is associated with specific cognitive abilities in older adults.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alterations of the prefrontal cortex (PFC) could contribute to cognitive decline in older adults. We examined the specificity of age-related PFC degeneration and whether cognitive abilities were related to volumetric measurements. Older and younger subjects were tested using a battery of tasks supported by different subregions within the PFC. The cognitive data from older subjects were related to PFC volumetric measurements in order to determine whether cortical morphology was predictive of individual differences in task performance within this age range (72-94 years). Working memory performance best distinguished older from younger subjects. Working memory measures but not other measures were correlated with age in both groups. A larger orbital PFC volume was related to a worse working memory performance and a larger superior PFC volume was related to worse conditional association learning. The volumes of these regions were not related to performance on other tasks. These results suggest that working memory is a sensitive measure of cognitive aging and that regional morphology is associated with specific cognitive abilities in older adults.
Fischl, Bruce; Salat, David H; Busa, Evelina; Albert, Marilyn; Dieterich, Megan; Haselgrove, Christian; van der Kouwe, Andre; Killiany, Ron; Kennedy, David; Klaveness, Shuna; Montillo, Albert; Makris, Nikos; Rosen, Bruce; Dale, Anders M
Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain Journal Article
In: Neuron, vol. 33, no. 3, pp. 341–355, 2002, ISSN: 0896-6273.
@article{pmid11832223,
title = {Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain},
author = {Bruce Fischl and David H Salat and Evelina Busa and Marilyn Albert and Megan Dieterich and Christian Haselgrove and Andre van der Kouwe and Ron Killiany and David Kennedy and Shuna Klaveness and Albert Montillo and Nikos Makris and Bruce Rosen and Anders M Dale},
doi = {10.1016/s0896-6273(02)00569-x},
issn = {0896-6273},
year = {2002},
date = {2002-01-01},
journal = {Neuron},
volume = {33},
number = {3},
pages = {341--355},
abstract = {We present a technique for automatically assigning a neuroanatomical label to each voxel in an MRI volume based on probabilistic information automatically estimated from a manually labeled training set. In contrast to existing segmentation procedures that only label a small number of tissue classes, the current method assigns one of 37 labels to each voxel, including left and right caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and amygdala. The classification technique employs a registration procedure that is robust to anatomical variability, including the ventricular enlargement typically associated with neurological diseases and aging. The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer's disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present a technique for automatically assigning a neuroanatomical label to each voxel in an MRI volume based on probabilistic information automatically estimated from a manually labeled training set. In contrast to existing segmentation procedures that only label a small number of tissue classes, the current method assigns one of 37 labels to each voxel, including left and right caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and amygdala. The classification technique employs a registration procedure that is robust to anatomical variability, including the ventricular enlargement typically associated with neurological diseases and aging. The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer's disease.
0000
Logue, Mark W.; van Rooij, Sanne J. H.; Dennis, Emily L.; Davis, Sarah L.; Hayes, Jasmeet P.; Stevens, Jennifer S.; Densmore, Maria; Haswell, Courtney C.; Ipser, Jonathan; Koch, Saskia B. J.; Korgaonkar, Mayuresh; Lebois, Lauren A. M.; Peverill, Matthew; Baker, Justin T.; Boedhoe, Premika S. W.; Frijling, Jessie L.; Gruber, Staci A.; Harpaz-Rotem, Ilan; Jahanshad, Neda; Koopowitz, Sheri; Levy, Ifat; Nawijn, Laura; O’Connor, Lauren; Olff, Miranda; Salat, David H.; Sheridan, Margaret A.; Spielberg, Jeffrey M.; van Zuiden, Mirjam; Winternitz, Sherry R.; Wolff, Jonathan D.; Wolf, Erika J.; Wang, Xin; Wrocklage, Kristen; Abdallah, Chadi G.; Bryant, Richard A.; Geuze, Elbert; Jovanovic, Tanja; Kaufman, Milissa L.; King, Anthony P.; Krystal, John H.; Lagopoulos, Jim; Bennett, Maxwell; Lanius, Ruth; Liberzon, Israel; McGlinchey, Regina E.; McLaughlin, Katie A.; Milberg, William P.; Miller, Mark W.; Ressler, Kerry J.; Veltman, Dick J.; Stein, Dan J.; Thomaes, Kathleen; Thompson, Paul M.; Morey, Rajendra A.
In: Biological Psychiatry, vol. 83, no. 3, pp. 244–253, 0000, ISSN: 0006-3223.
@article{Logue2018,
title = {Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia},
author = {Mark W. Logue and Sanne J.H. van Rooij and Emily L. Dennis and Sarah L. Davis and Jasmeet P. Hayes and Jennifer S. Stevens and Maria Densmore and Courtney C. Haswell and Jonathan Ipser and Saskia B.J. Koch and Mayuresh Korgaonkar and Lauren A.M. Lebois and Matthew Peverill and Justin T. Baker and Premika S.W. Boedhoe and Jessie L. Frijling and Staci A. Gruber and Ilan Harpaz-Rotem and Neda Jahanshad and Sheri Koopowitz and Ifat Levy and Laura Nawijn and Lauren O’Connor and Miranda Olff and David H. Salat and Margaret A. Sheridan and Jeffrey M. Spielberg and Mirjam van Zuiden and Sherry R. Winternitz and Jonathan D. Wolff and Erika J. Wolf and Xin Wang and Kristen Wrocklage and Chadi G. Abdallah and Richard A. Bryant and Elbert Geuze and Tanja Jovanovic and Milissa L. Kaufman and Anthony P. King and John H. Krystal and Jim Lagopoulos and Maxwell Bennett and Ruth Lanius and Israel Liberzon and Regina E. McGlinchey and Katie A. McLaughlin and William P. Milberg and Mark W. Miller and Kerry J. Ressler and Dick J. Veltman and Dan J. Stein and Kathleen Thomaes and Paul M. Thompson and Rajendra A. Morey},
doi = {10.1016/j.biopsych.2017.09.006},
issn = {0006-3223},
urldate = {2018-02-00},
journal = {Biological Psychiatry},
volume = {83},
number = {3},
pages = {244--253},
publisher = {Elsevier BV},
abstract = {Background
Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group.
Methods
We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium.
Results
In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063).
Conclusions
Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group.
Methods
We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium.
Results
In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063).
Conclusions
Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma.
Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group.
Methods
We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium.
Results
In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063).
Conclusions
Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma.