Weak correlations between body height and several brain metrics in healthy elderly subjects

The question whether body height is related to different brain size measures has recently gained renewed interest as some studies have reported that body height correlates with intelligence and several brain size measures. In this study, we re‐evaluated this question by examining the relationship between body height and different brain size measures including intracranial volume, total brain volume, total cortical surface area, total cortical volume, volume of normal‐appearing white matter, white matter hyperintensity, cortical surface area, cortical thickness, subcortical grey matter volume, cerebellar cortex and cerebellar white matter in a relatively large sample (n = 216) of physically and cognitively healthy elderly subjects (mean age 71 years, age range 65–85 years). We identified small correlations (r = .11–.19) between body height and seven out of 10 brain metrics (total brain volume, cortical surface area, cortical volume, subcortical volume, normal‐appearing white matter volume and cerebellar grey as well as white matter volumes) when controlling for sex and age. Based on these small relationships between body height and various brain size measures, we discuss the possible reasons and theoretical problems for these small relationships.     

The effect of meditation on brain structure: cortical thickness mapping and diffusion tensor imaging

A convergent line of neuroscientific evidence suggests that meditation alters the functional and structural plasticity of distributed neural processes underlying attention and emotion. The purpose of this study was to examine the brain structural differences between a well-matched sample of long-term meditators and controls. We employed whole-brain cortical thickness analysis based on magnetic resonance imaging, and diffusion tensor imaging to quantify white matter integrity in the brains of 46 experienced meditators compared with 46 matched meditation-naïve volunteers. Meditators, compared with controls, showed significantly greater cortical thickness in the anterior regions of the brain, located in frontal and temporal areas, including the medial prefrontal cortex, superior frontal cortex, temporal pole and the middle and interior temporal cortices. Significantly thinner cortical thickness was found in the posterior regions of the brain, located in the parietal and occipital areas, including the postcentral cortex, inferior parietal cortex, middle occipital cortex and posterior cingulate cortex. Moreover, in the region adjacent to the medial prefrontal cortex, both higher fractional anisotropy values and greater cortical thickness were observed. Our findings suggest that long-term meditators have structural differences in both gray and white matter.     

Brain and intracranial cavity volumes: in vivo determination by MRI

Brain volume is altered by pathological processes such as swelling or atrophy yet until now this is a parameter which could only be determined at post mortem. This paper describes a non-invasive technique using MRI which permits the in vivo determination of brain volume (BV), intracranial cavity volume (ICV), ventricular, cortical sulcal and total intracranial CSF volumes. The technique was applied to 40 normal volunteers (20 males, 20 females) to investigate the variation of these parameters with age and sex after normalisation with respect to ICV. There was found to be a significant decrease in normalised brain volume between the ages of 20 and 60 years in males by 1.6% per decade. In females the decrease was less (0.5%) but was not statistically significant. This technique will make it possible, for the first time, to investigate prospectively the correlation between mental function and brain volume in illness and ageing.     

The effect of white matter signal abnormalities on default mode network connectivity in mild cognitive impairment

Regions within the default mode network (DMN) are particularly vulnerable to Alzheimer's disease pathology and mechanisms of DMN disruption in mild cognitive impairment (MCI) are still unclear. White matter lesions are presumed to be mechanistically linked to vascular dysfunction whereas cortical atrophy may be related to neurodegeneration. We examined associations between DMN seed‐based connectivity, white matter lesion load, and cortical atrophy in MCI and cognitively healthy controls. MCI showed decreased functional connectivity (FC) between the precuneus‐seed and bilateral lateral temporal cortex (LTC), medial prefrontal cortex (mPFC), posterior cingulate cortex, and inferior parietal lobe compared to those with controls. When controlling for white matter lesion volume, DMN connectivity differences between groups were diminished within bilateral LTC, although were significantly increased in the mPFC explained by significant regional associations between white matter lesion volume and DMN connectivity only in the MCI group. When controlling for cortical thickness, DMN FC was similarly decreased across both groups. These findings suggest that white matter lesions and cortical atrophy are differentially associated with alterations in FC patterns in MCI. Associations between white matter lesions and DMN connectivity in MCI further support at least a partial but important vascular contribution to age‐associated neural and cognitive impairment.     

Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy.

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.     

Loss of entorhinal cortex and hippocampal volumes compared to whole brain volume in normal aging: The SMART-Medea study

In non-demented elderly age-related decline in hippocampal volume has often been observed, but it is not clear if this loss is disproportionate relative to other brain tissue. Few studies examined age-related volume loss of the entorhinal cortex. We investigated the association of age with hippocampal and entorhinal cortex (ERC) volumes in a large sample of middle-aged and older persons without dementia. Within the SMART-Medea study, cross-sectional analyses were performed in 453 non-demented subjects (mean age 62±9years, 81% male) with a history of arterial disease. Hippocampal and ERC volumes were assessed by manual segmentation on three-dimensional fast field-echo sequence T1-weighted magnetic resonance images. Automated segmentation was used to quantify volumes of BV and ICV. Hippocampal and ERC volumes were divided by intracranial volume (ICV) as well as total brain volume (BV) to determine whether age-related differences were disproportionate relative to other brain tissue. Total crude hippocampal volume was 5.96±0.7ml and total crude ERC volume was 0.34±0.06ml. Linear regression analyses adjusted for sex showed that with increasing age, hippocampal volume divided by ICV decreased (B per year older=-0.01ml; 95% CI -0.02 to -0.004). However, no age-related decline in hippocampal volume relative to BV was observed (B per year older=0.005ml; 95% CI -0.002 to 0.01). No age-related decline in ERC volume relative to ICV or BV was observed. In this population of nondemented patients with a history of vascular disease no age-related decline in entorhinal cortex volume was observed and although hippocampal volume decreased with age, it was not disproportionate relative to total brain volume.     

Ventricular dilatation and brain atrophy of normal elderly individuals and patients with Alzheimer-type dementia: A retrospective longitudinal computed tomographic study of autopsy cases

A retrospective longitudinal study of autopsy cases was performed in order to investigate the time course of ventricular dilatation and brain atrophy in normal individuals and patients with Alzheimer-type dementia (ATD) subjects over 70 years of age. The brains of eight non-demented individuals with no neurological or psychiatric illness (normal subjects, aged between 73 and 91 years), and the brains of seven ATD subjects (aged 68–96 years) were studied. The clinical records, including computed tomographic (CT) films, and autopsy findings were examined to eliminate subjects with conditions other than ATD. The rate of ventricular dilatation and brain atrophy was determined by volumetric measurement using serial CT films. Alzheimer-type dementia was diagnosed on the basis of clinical findings, the presence of laminar cortical degeneration of the medial temporal cortex, and the density of senile plaques and neurofibrillary tangles. Ventricular dilatation was not detected in the normal subjects but was detected in the ATD patients during the follow-up period. Brain atrophy was detected in both groups of subjects. However, the mean rate of brain atrophy of the ATD subjects was four times greater than that in the normal subjects. In addition, brain atrophy was accompanied by ventricular dilatation in all of the ATD patients, but was not evident in six of the eight normal subjects. Thus, the rate of ventricular dilatation was correlated with that of brain atrophy in the ATD patients, but not in the normal subjects. These results show that after 70 years of age: (i) the ventricular dilatation in normal subjects probably does not progress; (ii) brain atrophy in most normal subjects may continue; and (iii) rapidly progressive brain atrophy with ventricular dilatation is probably a common characteristic of ATD patients.     

Age-associated changes in rhesus CNS composition identified by MRI

Multispectral automated segmentation of MR images of the brains of 10 young (5-8 years), 10 middle-aged (12-17 years), and 11 old (21-27 years) female rhesus monkeys revealed age-associated changes in brain volume and composition. Total brain parenchymal volume (expressed as fraction of intracranial volume-%ICV) decreased at a linear rate of 0.3+/-0.04% ICV/year. Up to age approximately 15 years, this loss was almost entirely due to gray matter loss, with a compensatory increase in cerebrospinal fluid (CSF), and possibly some white matter. Brain tissue composition, expressed as the gray matter/white matter volume ratio confirmed that gray matter loss exceeded white matter loss, but the rate of decline in the gray/white ratio began to slow after approximately 15 years. Comparison of these age-associated changes in rhesus brain with those in humans suggest that the brain aging in rhesus is a good model of human brain aging, but occurs approximately 3-fold faster.     

Brain atrophy in chronic alcoholic patients: a quantitative pathological study.

There are essentially no objective neuropathological data on brain atrophy in chronic alcoholic patients despite numerous neuroradiological studies which show a high incidence of shrinkage or atrophy. Therefore measurements were made of the intracranial volume (ICV) and brain volume (BV) in a necropsy study of 25 chronic alcoholic patients and 44 controls. The pericerebral space (PICS) was calculated according to the formula (formula; see text) The PICS will increase in patients with brain atrophy since the ICV remains constant throughout life. The mean PICS value was 8.3% in controls, 11.3% in the alcoholic group, 14.7% in alcoholics with superimposed Wernicke's encephalopathy (thiamine deficiency) and 16.2% in those alcoholics with associated liver disease. Thus there was a statistically significant loss of brain tissue in chronic alcoholic patients which appeared to be more severe in those with associated nutritional vitamin deficiencies or alcoholic liver disease.     

Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder.

BACKGROUND: Reduced hippocampal volumes in posttraumatic stress disorder (PTSD) patients are thought to reflect specific changes of this structure. Previous magnetic resonance imaging (MRI) studies have not consistently examined indices of overall brain atrophy, therefore it cannot be completely ruled out that hippocampal changes are explained by whole-brain atrophy. The purpose of this study was to assess hippocampal and whole-brain volume in civilian PTSD. METHODS: Twelve subjects with PTSD and 10 control subjects underwent brain MRI. Hippocampal volumes were visually quantified using a computerized volumetric program. Whole-brain volumes were obtained with automated k-means-based segmentation. RESULTS: No differences were found in intracranial volumes (ICV). Subjects with PTSD had higher cerebrospinal fluid (CSF)/ICV ratios and lower white matter/ICV ratios, consistent with generalized white matter (WM) atrophy. The effect of age on CSF/ICV was more pronounced in the PTSD group. Subjects with PTSD had smaller absolute and normalized bilateral hippocampal volumes. These differences persisted after adjusting for lifetime weeks of alcohol intoxication. Posttraumatic stress disorder and depression scores correlated negatively with left hippocampal volume, but PTSD scores were a better predictor of hippocampal volumes. CONCLUSIONS: Our results replicate previous findings of reduced hippocampal volume in PTSD but also suggest independent, generalized, white matter atrophy.     

Association of white matter lesions and brain atrophy with the development of dementia in a community: the Hisayama Study

Aim

To investigate the association of white matter lesions volume (WMLV) levels with dementia risk and the association between dementia risk and the combined measures of WMLV and either total brain atrophy or dementia-related gray matter atrophy in a general older population.

Methods

One thousand one hundred fifty-eight Japanese dementia-free community-residents aged ≥65 years who underwent brain magnetic resonance imaging were followed for 5.0 years. WMLV were segmented using the Lesion Segmentation Toolbox. Total brain volume (TBV) and regional gray matter volume were estimated by voxel-based morphometry. The WMLV-to-intracranial brain volume ratio (WMLV/ICV) was calculated, and its association with dementia risk was estimated using Cox proportional hazard models. Total brain atrophy, defined as the TBV-to-ICV ratio (TBV/ICV), and dementia-related regional brain atrophy defined based on our previous report were calculated. The association between dementia risk and the combined measures of WMLV/ICV and either total brain atrophy or the number of atrophied regions was also tested.

Results

During the follow-up, 113 participants developed dementia. The risks of dementia increased significantly with higher WMLV/ICV levels. In addition, dementia risk increased additively both in participants with higher WMLV/ICV levels and lower TBV/ICV levels and in those with higher WMLV/ICV levels and a higher number of dementia-related brain regional atrophy.

Conclusion

The risk of dementia increased significantly with higher WMLV/ICV levels. An additive increment in dementia risk was observed with higher WMLV/ICV levels and lower TBV/ICV levels or a higher number of dementia-related brain regional atrophy, suggesting the importance of prevention or control of cardiovascular risk factors.     

Regional brain morphometry and lissencephaly in the Sirenia

Neuroanatomical structure was examined in the brains of West Indian manatees (Trichechus manatus) using computer-based morphometric methods. Although manatees have a small relative brain size, volume estimates of the major brain regions indicate that the telencephalon comprises 71% of total brain volume and is 90% cerebral cortex. These values are comparable to those seen among a diversity of taxa having large relative brain size, including many primates. Manatee brains also exhibit well-defined cortical lamination. The measured gyration index (an index of cortical folding) was 1.06, representing a highly lissencephalic condition. These findings demonstrate that small relative brain size and lissencephaly do not constrain the elaboration of internal brain structures. The marked lissencephalic condition is unusual for brains of this absolute size range, and may be related to the thickness of the cortical gray matter and underlying white matter.     

Regional Specificity of Brain Atrophy in Huntington''s Disease

The present study analyzes the relationship between cortical and subcortical brain volumes in patients with Huntington's disease. The brains of seven patients with a clinical diagnosis and positive family history of Huntington's disease and 12 controls were collected at autopsy with consent from relatives. Detailed clinical assessments were available for all study subjects with genotype confirmation for patients with Huntington's disease. Volume analysis of the brain on serial 3-mm coronal slices was performed as previously described. All patients with Huntington's disease exhibited significant brain atrophy resulting from volume reductions in both cortical and subcortical grey matter. Atrophy of the cortex was relatively uniform, although the medial temporal lobe structures were spared. The caudate nucleus and putamen were strikingly reduced in all cases and this atrophy correlated with the severity of cortical atrophy, suggesting an associated disease process. The rate of cortical but not subcortical atrophy correlated with CAG repeat numbers. Loss of frontal white matter correlated with both cortical and striatal atrophy. Age of onset of chorea correlated with the amount of subcortical atrophy, while duration of chorea correlated negatively with atrophy of the white matter. These results suggest a more widespread and global disease process in patients with Huntington's disease.     

Intracranial cerebrospinal fluid measurement studies in suspected idiopathic normal pressure hydrocephalus,secondary normal pressure hydrocephalus,and brain atrophy

OBJECTIVE: To investigate intracranial cerebrospinal fluid (CSF) distribution in patients with a clinical diagnosis of idiopathic normal pressure hydrocephalus (INPH). METHODS: 24 patients with a clinical diagnosis of INPH were studied. Control groups comprised 17 patients with secondary normal pressure hydrocephalus (SNPH), 21 patients with brain atrophy, and 18 healthy volunteers. Ventricular volume (VV) and intracranial CSF volume (ICV) were measured using a magnetic resonance based method and the VV/ICV ratio was calculated. RESULTS: The SNPH group showed a marked increase in the VV/ICV ratio compared with the healthy volunteers (37.8% v 15.6%, p < 0.0001). The brain atrophy group showed a significant increase in ICV compared with the healthy volunteers (284.4 ml v 194.7 ml, p =0.0002). The INPH group showed an increase in ICV (281.2 ml, p = 0.0002) and an increase in the VV/ICV ratio (38.0%, p < 0.0001). Fifteen of 24 INPH patients underwent shunting; 11 improved and four did not. CONCLUSIONS: The results suggest that INPH patients have brain atrophy in addition to hydrocephalic features. This may help to explain the difficulties encountered in the diagnosis and the unpredictable response rate to shunt surgery in INPH patients.     

Patterns of cortical thinning in idiopathic rapid eye movement sleep behavior disorder

Idiopathic rapid eye movement sleep behavior disorder is a parasomnia that is a risk factor for dementia with Lewy bodies and Parkinson's disease. Brain function impairments have been identified in this disorder, mainly in the frontal and posterior cortical regions. However, the anatomical support for these dysfunctions remains poorly understood. We investigated gray matter thickness, gray matter volume, and white matter integrity in patients with idiopathic rapid eye movement sleep behavior disorder. Twenty‐four patients with polysomnography‐confirmed idiopathic rapid eye movement sleep behavior disorder and 42 healthy individuals underwent a 3‐tesla structural and diffusion magnetic resonance imaging examination using corticometry, voxel‐based morphometry, and diffusion tensor imaging. In the patients with idiopathic rapid eye movement sleep behavior disorder, decreased cortical thickness was observed in the frontal cortex, the lingual gyrus, and the fusiform gyrus. Gray matter volume was reduced in the superior frontal sulcus only. Patients showed no increased gray matter thickness or volume. Diffusion tensor imaging analyses revealed no significant white matter differences between groups. Using corticometry in patients with idiopathic rapid eye movement sleep behavior disorder, several new cortical regions with gray matter alterations were identified, similar to those reported in dementia with Lewy bodies and Parkinson's disease. These findings provide some anatomical support for previously identified brain function impairments in this disorder. © 2014 International Parkinson and Movement Disorder Society     

Brain volumetric MRI study in healthy elderly persons using statistical parametric mapping]

PURPOSE: To investigate the age-related changes in the brains of healthy elderly subjects, a volumetric MRI was performed using Statistical Parametric Mapping (SPM) and Region of Interest (ROI) methods. We determined the volumes of the whole brain, the gray matter, the prefrontal cortex, the hippocampus and the entorhinal cortex. SUBJECTS AND METHODS: We examined 61 subjects (29 males and 32 females) aged 61 to 91 years (mean +/- SD = 72.4 +/- 7.85) who were residents of Okinawa prefecture, living at home and highly active as demonstrated by sustained participation in senior citizens clubs and/or group activities at senior citizen welfare centers. They had no history of psychiatric disorders, neurological or significant physical illness. They had Mini-Mental State Examination scores of 24 or above (mean +/- SD = 28.3 +/- 1.57), Japanese version of the Geriatric Depression Scale scores of 9 or below, and Tokyo Metropolitan Institute of Gerontology scores of 11 or above. All subjects were dextral. This study received prior approval by the participating medical institution. Informed consent was obtained from the individual subjects. Volumetric MRI was performed using a 1.5 Tesla MRI scanner (Magnetom Vision, Siemens). T1-weighted images were acquired in the coronal plane (perpendicular to anterior commissure-posterior commissure line) using a 3D-FLASH (fast low angle shot) sequence. Imaging parameters were: TR = 35 ms, TE = 5 ms, Flip angle = 45 deg., Field of View = 240 mm, Matrix 256 x 256, Pixel 0.9375 x 0.9375, Slice thickness 1.5 mm, Gapless. MR image data were analyzed by SPM using an imaging analysis software MEDx (Sensor Systems Inc.) running on UNIX workstation (Sun SPARC Solaris 7, Sun Microsystems, Inc.). Volumetry was performed by automatic segmentation technique using SPM for the whole brain and the gray matter, and manual tracing using ROI based quantitative methods for the prefrontal cortex, the hippocampus and the entorhinal cortex. Local volumes were normalized by the intracranial volume and the gray matter volume. Correlation to age was determined by Pearson's correlation coefficient. Volumetric MRI was performed under blinded conditions. RESULTS: Volumetric MRI of normal brain in healthy elderly subjects showed age-related changes. The whole brain (r = -0.568, p < 0.01), the gray matter (r = -0.406, p < 0.01), the prefrontal cortex (r = -0.470, p < 0.01), the hippocampus (r = -0.305, p < 0.05), and the entorhinal cortex (r = -0.455, p < 0.01) volume significantly decreased with age. The age-related hippocampal volume reduction was similar to the gray matter reduction, but the age-related prefrontal cortex and entorhinal cortex volume reductions were greater than the gray matter volume reduction. The prefrontal cortex and the hippocampal volumes differed by sex, being greater in females (p < 0.05). The hippocampal volume was lateralized: right side was greater than the left (p < 0.01). The entorhinal cortex volume was lateralized so that the left side was greater than the right (p < 0.01). CONCLUSION: As a result of volumetric MRI using SPM, age-related changes of normal brain in healthy elderly persons did not always show unified atrophy. The ratio of atrophy was different by a local area. Our findings suggested that the most marked age-related brain volume reductions were seen in the prefrontal cortex and the entorhinal cortex. The age-related hippocampal volume reduction was similar to the gray matter reduction.     

Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease

OBJECTIVE: To examine volumetric MRI correlates of longitudinal cognitive decline in normal aging, AD, and subcortical cerebrovascular brain injury (SCVBI). BACKGROUND: Previous cross-sectional studies examining the relationship between cognitive impairment and dementia have shown that hippocampal and cortical gray matter atrophy are the most important predictors of cognitive impairment, even in cases with SCVBI. The authors hypothesized that hippocampal and cortical gray matter volume also would best predict rate of cognitive decline in cases with and without SCVBI. METHODS: Subjects were recruited for a multicenter study of contributions to dementia of AD and SCVBI. The sample (n = 120) included cognitively normal, cognitively impaired, and demented cases with and without lacunes identified by MRI. Cases with cortical strokes were excluded. Average length of follow-up was 3.0 years. Measures of hippocampal volume, volume of cortical gray matter, presence of subcortical lacunes, and volume of white matter hyperintensity were derived from MRI. Random effects modeling of longitudinal data was used to assess effects of baseline MRI variables on longitudinal change in a measure of global cognitive ability. RESULTS: Cortical gray matter atrophy predicted cognitive decline regardless of whether lacunes were present. Hippocampal atrophy predicted decline only in those without lacunes. Neither lacunes nor white matter hyperintensity independently predicted decline. CONCLUSIONS: Results suggest that cortical atrophy is an index of disease severity in both AD and subcortical cerebrovascular brain injury and consequently predicts faster progression. Hippocampal volume may index disease severity and predict progression in AD. The absence of this effect in cases with lacunes suggests that this group is etiologically heterogeneous and is not composed simply of cases of AD with incidental stroke.     

Longitudinal brain atrophy distribution in advanced Parkinson's disease: What makes the difference in “cognitive status” converters?

We investigated the brain atrophy distribution pattern and rate of regional atrophy change in Parkinson's disease (PD) in association with the cognitive status to identify the morphological characteristics of conversion to mild cognitive impairment (MCI) and dementia (PDD). T1‐weighted longitudinal 3T MRI data (up to four follow‐up assessments) from neuropsychologically well‐characterized advanced PD patients (n = 172, 8.9 years disease duration) and healthy elderly controls (n = 85) enrolled in the LANDSCAPE study were longitudinally analyzed using a linear mixed effect model and atlas‐based volumetry and cortical thickness measures. At baseline, PD patients presented with cerebral atrophy and cortical thinning including striatum, temporoparietal regions, and primary/premotor cortex. The atrophy was already observed in “cognitively normal” PD patients (PD‐N) and was considerably more pronounced in cognitively impaired PD patients. Linear mixed effect modeling revealed almost similar rates of atrophy change in PD and controls. The group comparison at baseline between those PD‐N whose cognitive performance remained stable (n = 42) and those PD‐N patients who converted to MCI/PDD (“converter” cPD‐N, n = 26) indicated suggested cortical thinning in the anterior cingulate cortex in cPD‐N patients which was correlated with cognitive performance. Our results suggest that cortical brain atrophy has been already expanded in advanced PD patients without overt cognitive deficits while atrophy progression in late disease did not differ from “normal” aging regardless of the cognitive status. It appears that cortical atrophy begins early and progresses already in the initial disease stages emphasizing the need for therapeutic interventions already at disease onset.     

Gray matter integrity predicts white matter network reorganization in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease leading to gray matter atrophy and brain network reconfiguration as a response to increasing tissue damage. We evaluated whether white matter network reconfiguration appears subsequently to gray matter damage, or whether the gray matter degenerates following alterations in white matter networks. MRI data from 83 patients with clinically isolated syndrome and early relapsing–remitting MS were acquired at two time points with a follow‐up after 1 year. White matter network integrity was assessed based on probabilistic tractography performed on diffusion‐weighted data using graph theoretical analyses. We evaluated gray matter integrity by computing cortical thickness and deep gray matter volume in 94 regions at both time points. The thickness of middle temporal cortex and the volume of deep gray matter regions including thalamus, caudate, putamen, and brain stem showed significant atrophy between baseline and follow‐up. White matter network dynamics, as defined by modularity and distance measure changes over time, were predicted by deep gray matter volume of the atrophying anatomical structures. Initial white matter network properties, on the other hand, did not predict atrophy. Furthermore, gray matter integrity at baseline significantly predicted physical disability at 1‐year follow‐up. In a sub‐analysis, deep gray matter volume was significantly related to cognitive performance at baseline. Hence, we postulate that atrophy of deep gray matter structures drives the adaptation of white matter networks. Moreover, deep gray matter volumes are highly predictive for disability progression and cognitive performance.     

Brain Structure in Neuropsychologically Defined Subgroups of Schizophrenia and Psychotic Bipolar Disorder

Background:

Neuropsychological impairment is heterogeneous in psychosis. The association of intracranial volume (ICV) and total brain volume (TBV) with cognition suggests brain structure abnormalities in psychosis will covary with the severity of cognitive impairment. We tested the following hypotheses: (1) brain structure abnormalities will be more extensive in neuropsychologically impaired psychosis patients; (2) psychosis patients with premorbid cognitive limitations will show evidence of hypoplasia (ie, smaller ICV); and (3) psychosis patients with evidence of cognitive decline will demonstrate atrophy (ie, smaller TBV, but normal ICV).

Methods:

One hundred thirty-one individuals with psychosis and 97 healthy subjects underwent structural magnetic resonance imaging and neuropsychological testing. Patients were divided into neuropsychologically normal and impaired groups. Impaired patients were further subdivided into deteriorated and compromised groups if estimated premorbid intellect was average or below average, respectively. ICV and TBV were compared across groups. Localized brain volumes were qualitatively examined using voxel-based morphometry.

Results:

Compared to healthy subjects, neuropsychologically impaired patients exhibited smaller TBV, reduced grey matter volume in frontal, temporal, and subcortical brain regions, and widespread white matter volume loss. Neuropsychologically compromised patients had smaller ICV relative to healthy subjects, and neuropsychologically normal and deteriorated patient groups, but relatively normal TBV. Deteriorated patients exhibited smaller TBV compared to healthy subjects, but relatively normal ICV. Unexpectedly, TBV, adjusted for ICV, was reduced in neuropsychologically normal patients.

Conclusions:

Patients with long-standing cognitive limitations exhibit evidence of early cerebral hypoplasia, whereas neuropsychologically normal and deteriorated patients show evidence of brain tissue loss consistent with progression or later cerebral dysmaturation.Key words: psychosis, cognition, brain volume, neurodevelopmental, neuroprogressive