Interindividual differences in gray and white matter properties are associated with early complex motor skill acquisition

Brain circuits mediate but also constrain experience‐induced plasticity and corresponding behavioral changes. Here we tested whether interindividual behavioral differences in learning a challenging new motor skill correlate with variations in brain anatomy. Young, healthy participants were scanned using structural magnetic resonance imaging (T1‐weighted MPRAGE, n = 75 and/or diffusion‐weighted MRI, n = 59) and practiced a complex whole‐body balancing task on a seesaw‐like platform. Using conjunction tests based on the nonparametric combination (NPC) methodology, we found that gray matter volume (GMV) in the right orbitrofrontal cortex was positively related to the subjects' initial level of proficiency and their ability to improve performance during practice. Similarly, we obtained a strong trend toward a positive correlation between baseline fractional anisotropy (FA) in commissural prefrontal fiber pathways and later motor learning. FA results were influenced more strongly by radial than axial diffusivity. However, we did not find unique anatomical correlates of initial performance and learning to rate. Our findings reveal structural predispositions for successful motor skill performance and acquisition in frontal brain structures and underlying frontal white matter tracts. Together with previous results, these findings support the view that structural constraints imposed by the brain determine subsequent behavioral success and underline the importance of structural brain network constitution before learning starts.     

Patterns of regional gray matter and white matter atrophy in cortical multiple sclerosis

We investigated the patterns of regional distribution of focal lesions, white matter (WM) and gray matter (GM) atrophy in patients with cortical (cort) MS in comparison to classical (c) MS patients. Nine cort-MS, nine c-MS and nine age-matched healthy controls (HC) underwent a brain MRI exam, including FLAIR and high-resolution T1-weighted scans. MS patients underwent neurological and neuropsychological assessment. Between-group differences of GM and WM volumes and their correlations with neuropsychological performances were assessed with voxel-based morphometry. FLAIR and T1 lesion probability maps (LPMs) were also obtained. Performance at neuropsychological tests was worse in cort-MS than in c-MS patients. Compared to HC, MS patients had a distributed pattern of GM and WM atrophy. No GM/WM area was more atrophic in c-MS vs cort-MS patients. Compared to c-MS, cort-MS patients experienced GM atrophy of frontal–temporal–parietal areas and cingulate cortex and WM atrophy of the cingulum bundle, bilateral cerebral peduncles, right inferior longitudinal fasciculus and left superior longitudinal fasciculus. FLAIR and T1 LPMs did not differ between c-MS vs cort-MS patients. A higher susceptibility to neurodegenerative processes in key brain regions known to be related to cognitive functions is likely to underlie the clinical manifestations of cort-MS.     

A forward application of age associated gray and white matter networks

To capture patterns of normal age-associated atrophy, we previously used a multivariate statistical approach applied to voxel based morphometry that identified age-associated gray and white matter covariance networks (Brickman et al. [2007]: Neurobiol Aging 28:284-295). The current study sought to examine the stability of these patterns by forward applying the identified networks to an independent sample of neurologically healthy younger and older adults. Forty-two younger and 35 older adults were imaged with standard high-resolution structural magnetic resonance imaging. Individual images were spatially normalized and segmented into gray and white matter. Covariance patterns that were previously identified with scaled subprofile model analyses were prospectively applied to the current sample to identify to what degree the age-associated patterns were manifested. Older individuals were also assessed with a modified version of the Mini Mental State Examination (mMMSE). Gray matter covariance pattern expression discriminated between younger and older participants with high optimal sensitivity (100%) and specificity (90.5%). While the two groups differed in the degree of white matter pattern expression (t (75) = 5.26, P < 0.001), classification based on white matter expression was relatively low (sensitivity = 80% and specificity = 61.9%). Among older adults, chronological age was significantly associated with increased gray matter pattern expression (r (32) = 0.591, P < 0.001) but not with performance on the mMMSE (r (31) = -0.314, P = 0.085). However, gray matter pattern expression was significantly associated with performance on the mMMSE (r (31) = -0.405, P = 0.024). The findings suggest that the previously derived age-associated covariance pattern for gray matter is reliable and may provide information that is more functionally meaningful than chronological age.     

A voxel-based morphometry study of regional gray and white matter correlate of self-disclosure

Self-disclosure is an important performance in human social communication. Generally, an individual is likely to have a good physical and mental health if he is prone to self-disclosure under stressful life events. However, as for now, little is known about the neural structure associated with self-disclosure. Therefore, in this study, we used voxel-based morphometry to explore regional gray matter volume (rGMV) and white matter volume (rWMV) associated with self-disclosure measured by the Jourard Self-disclosure Questionnaire in a large sample of college students. Results showed that individual self-disclosure was significantly and positively associated with rGMV of the left postcentral gyrus, which might be related to strengthen individual’s ability of body feeling; while self-disclosure was significantly and negatively associated with rGMV of the right orbitofrontal cortex (OFC), which might be involved in increased positive emotion experience seeking (intrinsically rewarding). In addition, individual self-disclosure was also associated with smaller rWMV in the right inferior parietal lobule (IPL). These findings suggested a biological basis for individual self-disclosure, distributed across different gray and white matter areas of the brain.     

Deviations from normative brain white and gray matter structure are associated with psychopathology in youth

Combining imaging modalities and metrics that are sensitive to various aspects of brain structure and maturation may help identify individuals that show deviations in relation to same-aged peers, and thus benefit early-risk-assessment for mental disorders. We used one timepoint multimodal brain imaging, cognitive, and questionnaire data from 1280 eight- to twenty-one-year-olds from the Philadelphia Neurodevelopmental Cohort. We estimated age-related gray and white matter properties and estimated individual deviation scores using normative modeling. Next, we tested for associations between the estimated deviation scores, and with psychopathology domain scores and cognition. More negative deviations in DTI-based fractional anisotropy (FA) and the first principal eigenvalue of the diffusion tensor (L1) were associated with higher scores on psychosis positive and prodromal symptoms and general psychopathology. A more negative deviation in cortical thickness (CT) was associated with a higher general psychopathology score. Negative deviations in global FA, surface area, L1 and CT were also associated with poorer cognitive performance. No robust associations were found between the deviation scores based on CT and DTI. The low correlations between the different multimodal magnetic resonance imaging-based deviation scores suggest that psychopathological burden in adolescence can be mapped onto partly distinct neurobiological features.     

Structural gray and white matter changes in patients with HIV

In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 ± 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson’s Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder.     

Trait conscientiousness and the personality meta-trait stability are associated with regional white matter microstructure

Establishing the neural bases of individual differences in personality has been an enduring topic of interest. However, while a growing literature has sought to characterize grey matter correlates of personality traits, little attention to date has been focused on regional white matter correlates of personality, especially for the personality traits agreeableness, conscientiousness and openness. To rectify this gap in knowledge we used a large sample (n > 550) of older adults who provided data on both personality (International Personality Item Pool) and white matter tract-specific fractional anisotropy (FA) from diffusion tensor MRI. Results indicated that conscientiousness was associated with greater FA in the left uncinate fasciculus (β = 0.17, P < 0.001). We also examined links between FA and the personality meta-trait ‘stability’, which is defined as the common variance underlying agreeableness, conscientiousness, and neuroticism/emotional stability. We observed an association between left uncinate fasciculus FA and stability (β = 0.27, P < 0.001), which fully accounted for the link between left uncinate fasciculus FA and conscientiousness. In sum, these results provide novel evidence for links between regional white matter microstructure and key traits of human personality, specifically conscientiousness and the meta-trait, stability. Future research is recommended to replicate and address the causal directions of these associations.     

Plexin B3 is genetically associated with verbal performance and white matter volume in human brain

The presence of genetic influences on cognitive performance and brain volume is well established. However, specific genetic determinants of the variance of these quantitative traits are not yet known. Plexins act as receptors for semaphorins and are implicated in axon guidance, which is a key process in brain development. We have previously shown that plexin B3 is a highly potent stimulator of neurite outgrowth, which makes its gene PLXNB3 an intriguing candidate gene for traits related to human brain development and cerebral connectivity. We identified several polymorphisms in PLXNB3 predicting changes of amino acids (V598I, E1156D and V1596E) conserved at the corresponding positions of the orthologs in mouse and chimpanzee. PLXNB3 was genotyped in 303 healthy volunteers and 42 male patients with schizophrenia. Cognitive performance was measured with the vocabulary test (Wortschatztest (WST)), a method to estimate roughly general intelligence (g). Brain morphology was characterized by magnetic resonance imaging. Compared to subjects not carrying the modern, human-specific haplotype A, carriers of A scored higher in vocabulary test (WST) irrespective of diagnosis (P=0.0004). This effect could be observed in three independent groups (healthy males: P=0.048; schizophrenic males: P=0.034 and healthy females: P=0.037). Additionally, the haplotype A was associated with increased volume of brain white matter that in turn correlated with performance in the vocabulary test. These findings suggest that plexin B3 may influence cognitive performance, and the development of white matter in vivo in a way similar to its known stimulating effect on neurite outgrowth in vitro. These novel observations warrant further replication in independent samples.     

Elevated protein carbonylation in the brain white matter and gray matter of patients with multiple sclerosis

Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). Increased levels of reactive oxygen species (ROS) derived from infiltrating macrophages and microglial cells have been shown to reduce the levels of endogenous antioxidants and to cause the oxidation of various substrates within the MS plaque. To determine whether oxidative damage takes place beyond visible MS plaques, the occurrence of total carbonyls (TCOs) and protein carbonyls (PCOs) in the normal-appearing white matter (NAWM) and gray matter (NAGM) of eight MS brains was assessed and compared with those of four control brains. The data show that most (7/8) of the MS-WM samples contain increased amounts of PCOs as determined by reaction with 2,4-dinitrophenylhydrazine and Western blot analysis. These samples also have high levels of glial fibrilary acidic protein (GFAP), suggesting that oxidative damage is related to the presence of small lesions. In contrast, we detected no evidence of protein thiolation (glutathionylation and cysteinylation) in the diseased tissue. To our surprise, MS-NAGM specimens with high GFAP content also showed three times the concentration of TCOs and PCOs as the controls. The increase in PCOs is likely to be a consequence of reduced levels of antioxidants, in that the concentration of nonprotein thiols in both MS-WM and -GM decreased by 30%. Overall, our data support the current view that both NAWM and -GM from MS brains contain considerable biochemical alterations. The involvement of GM in MS was also supported by the decrease in the levels of neurofilament light protein in all the specimens analyzed. To the best of our knowledge, this is the first study demonstrating the presence of increased protein carbonylation in post-mortem WM and GM tissue of MS patients.     

Childhood trauma is associated with social anhedonia and brain gray matter volume differences in healthy subjects

Brain Imaging and Behavior - The present study tested the effects of childhood trauma (CT) on trait social anhedonia (SA) and on gray matter volume (GMV) and explored the possible relationships...     

Smoking is associated with reduced cortical regional gray matter density in brain regions associated with incipient Alzheimer disease.

OBJECTIVES: The results of observational studies suggest that smoking increases the risk of Alzheimer disease (AD). The authors designed this study to determine if older people who smoke have decreased gray matter density in brain regions associated with incipient AD. METHODS: The authors recruited 39 pairs (N = 78) of smokers/never-smokers 70 to 83 years of age who were matched for age, sex, education, and handedness. Participants were free of clinically significant cognitive impairment, depression, stroke, or other serious medical conditions. Gray matter density was determined by voxel-based morphometry using statistical parametric mapping of T1-weighted magnetic resonance images. RESULTS: Smokers had decreased gray matter density in the posterior cingulum and precuneus (bilateral), right thalamus, and frontal cortex (bilateral) compared with never-smokers. CONCLUSIONS: Smoking is associated with decreased gray matter density in brain regions previously associated with incipient AD. Longitudinal investigations are required to clarify whether these changes are progressive in nature.     

The scaling of white matter to gray matter in cerebellum and neocortex

It is known that the white matter of neocortex increases disproportionately with brain size. However, relatively few measurements have been made of white matter/gray matter scaling in the cerebellum. We present data on the volumes of white and gray matter in both structures, taken from 45 species of mammals. We find a scaling exponent of 1.13 for cerebellum and 1.28 for neocortex. The 95% confidence intervals for our estimates of these two exponents do not overlap. This difference likely reflects differences in the connectivity and/or micro-structure of white matter in the two regions.     

Relation between cerebrospinal fluid, gray matter and white matter changes in families with schizophrenia

BACKGROUND: Gray matter reduction and ventricular enlargement belong to the best replicated findings in schizophrenia. Brain morphologic changes were also found in non-schizophrenic family members (FM). The intention of this study was to examine whether non-psychotic first-degree relatives reveal similar morphologic changes as schizophrenic patients and how state of genetic loading contribute to these abnormalities. METHODS: Forty-nine schizophrenic patients, 71 non-schizophrenic FM and 48 control subjects took part in this volumetric MRI study. All subjects were between 18 and 59 years old. Dependent variables were gray matter, white matter and total cerebrospinal fluid (CSF) volume, determined by SPM99 segmentation algorithm. As an important part of CSF lateral ventricle volume was determined manually by removing surrounding CSF areas. RESULTS: In schizophrenic patients compared to controls and non-schizophrenic FM total CSF volumes and lateral ventricles were increased. Gray and, to a lesser degree, white matter volumes were decreased as well. For CSF, gray and white matter there was no significant difference between uni- and multiple affected families. CSF correlated significantly negative with gray matter (r=-0.78) and, less intensive, with white matter (r=-0.40). There were negative correlations between gray and white matter volume as well (r=-0.26). These correlations were not significantly different between the diagnostic groups. CONCLUSION: CSF enlargement and gray matter reductions in schizophrenic patients compared to controls and non-affected FM seem to be interdependent findings. However, this correlation is independent of the factor diagnosis and is therefore not specific for schizophrenia.     

Quantitative analysis of gray and white matter in Williams syndrome

Williams syndrome is a developmental disorder with a genetic basis, which results in an uneven cognitive profile with relatively strong language skills and severely impaired visuospatial abilities. To better understand the brain structure underlying this profile, we compared individuals with Williams syndrome with controls using multimodal neuroimaging data and new analytic methods (diffeomorphic mapping and atlas-based analysis). People with Williams syndrome had basal ganglia atrophy, while the fusiform, the medium temporal gyri, and the cerebellar cortex were relatively preserved. The right superior longitudinal fasciculus, the left frontooccipital fasciculus, the caudate, and the cingulum demonstrated increased fractional anisotropy, whereas the corticospinal tract revealed decreased values. These findings may be linked to the uneven cognitive profile evident in Williams syndrome.     

Gray matter volume differences and the effects of smoking on gray matter in schizophrenia

OBJECTIVE: Many studies have evaluated differences in gray matter volume in schizophrenia, but have not considered the possible effects of smoking, which is extraordinarily common in people with the illness. The present study used voxel-based morphometry (VBM) to examine differences in gray matter in subjects with schizophrenia and evaluate the effects of smoking on this measure. METHODS: Thirty-two subjects with schizophrenia (14 smokers, 18 non-smokers) and 32 healthy comparison subjects participated in the study. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). RESULTS: Reduced gray matter was observed in the schizophrenia group in the orbitofrontal cortex, bilateral insula and superior temporal gyri (STG), bilateral dorsolateral prefrontal cortices (DLPFC), medial frontal gyrus, and cingulate gyrus. Within this group, smoking subjects had greater lateral prefrontal and STG gray matter volumes relative to non-smoking subjects. CONCLUSIONS: The finding of reduced gray matter volume in prefrontal and temporal regions in schizophrenia is consistent with prior anatomical tracing and whole-brain voxel-based studies. Greater gray matter volumes in smoking relative to non-smoking subjects with schizophrenia highlight a potential experimental confound in volumetric studies and suggests that smoking may be associated with a relative preservation of lateral prefrontal and temporal gray matter in schizophrenia.