Lower White Matter Volume Research Articles

Dissociable morphometric profiles of the affective and cognitive dimensions of alexithymia

Alexithymia (“no words for feelings”) is a psychological construct that can be divided in a cognitive and affective dimension. The cognitive dimension reflects the ability to identify, verbalize and analyze feelings, whereas the affective dimension reflects the degree to which individuals get aroused by emotional stimuli and their ability to fantasize. These two alexithymia dimensions may differentially put individuals at risk to develop psychopathology. However, their neural correlates have rarely been investigated. The aim of the current study was to investigate whether the cognitive and affective alexithymia dimension are associated with unique anatomical profiles. Structural MRI scans of 57 participants (29 males; mean age: 34) were processed using a voxel-based morphometry (VBM) – Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL) approach. Multiple regression analyses were performed to examine the common and specific associations between gray and white matter volume and alexithymia subdimensions. The results revealed that the cognitive dimension was related to lower dorsal anterior cingulate volume. In contrast, the affective alexithymia was associated with lower gray matter volume in the medial orbitofrontal cortex (OFC) and lower white matter volume in the superior longitudinal fasciculus (SLF) near the angular gyrus. No relationship between corpus callosum volume and alexithymia was observed. These results are consistent with the idea that there are two separable neural systems underlying alexithymia. This finding might encourage future research into the link between specific alexithymia subtypes and the development of psychopathology.

Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers.

In children, CNS-directed cancer therapy is thought to result in decreased cerebral white matter volumes (WMV) and subsequent neurocognitive deficits. This study was designed as a prospective validation of the purported reduction in WMV, associated influential factors, and its relationship to neurocognitive deficits in a very large cohort of both acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) survivors in comparison to an age similar cohort of healthy sibling controls. The effects of host characteristics and CNS treatment intensity on WMV were investigated in 383 childhood cancer survivors (199 ALL, 184 BT) at least 12 months post-completion of therapy and 67 healthy siblings that served as a control group. t-Tests and multiple variable linear models were used to assess cross-sectional WMV and its relation with neurocognitive function. BT survivors had lower WMV than ALL survivors, who had less than the control group. Increased CNS treatment intensity, younger age at treatment, and greater time since treatment were significantly associated with lower WMV. Additionally, cancer survivors did not perform as well as the control group on neurocognitive measures of intelligence, attention, and academic achievement. Reduced WMV had a larger impact on estimated IQ among females and children treated at a younger age. Survivors of childhood cancer that have undergone higher intensity therapy at a younger age have significantly less WMV than their peers and this difference increases with time since therapy. Decreased WMV is associated with significantly lower scores in intelligence, attention, and academic performance in survivors.

Widespread decreased grey and white matter in paediatric obsessive-compulsive disorder (OCD): A voxel-based morphometric MRI study

Obsessive-compulsive disorder (OCD) is a chronic, relapsing anxiety disorder. To date, neuroimaging investigations of OCD have been variable and few studies have examined paediatric populations. Eight children with OCD and 12 typically developing children matched for age, gender, handedness and performance IQ underwent a high resolution T1-weighted structural magnetic resonance imaging (MRI) scan. A voxel-based morphometry (VBM) protocol (using DARTEL) compared the brains of the paediatric OCD children with those of typically developing children. Overall, children with OCD demonstrated significantly lower intra-cranial volume (ICV) and grey- and white-matter volumes. ICV was significantly reduced (∼9%) in the OCD group compared with the typically developing group. The VBM analysis demonstrated lower volumes in widespread grey matter in bilateral frontal, cingulate, temporal–parietal, occipital–frontal and right precuneus regions for OCD. Lower white matter volume was found bilaterally in the cingulate and occipital cortex, right frontal and parietal and left temporal regions, and the corpus callosum. In summary, this study provides further evidence of brain dysmorphology in paediatric OCD patients. In addition to fronto–striatal–thalamic neural networks, abnormalities in other brain regions, such as the parietal lobe and corpus callosum, were demonstrated. These brain regions may play an additional role in the pathophysiology of OCD.

The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives

We investigated the role of variation in putative psychosis genes coding for elements of the white matter system by examining the contribution of genotypic variation in three single-nucleotide polymorphisms (SNPs) neuregulin 1 (NRG1) SNP8NRG221533, myelin oligodendrocytes glycoprotein (MOG) rs2857766 and CNP (rs2070106) and one haplotype HAPICE (deCODE) to white matter volume in patients with psychotic disorder and their unaffected relatives. Structural magnetic resonance imaging and blood samples for genotyping were collected on 189 participants including patients with schizophrenia (SZ) or bipolar I disorder (BDI), unaffected first-degree relatives of these patients and healthy volunteers. The association of genotypic variation with white matter volume was assessed using voxel-based morphometry in SPM5. The NRG1 SNP and the HAPICE haplotype were associated with abnormal white matter volume in the BDI group in the fornix, cingulum and parahippocampal gyrus circuit. In SZ the NRG1 SNP risk allele was associated with lower white matter volume in the uncinate fasciculus (UF), right inferior longitudinal fasciculus and the anterior limb of the internal capsule. Healthy G-homozygotes of the MOG SNP had greater white matter volume in areas of the brainstem and cerebellum; this relationship was absent in those with a psychotic disorder and the unaffected relatives groups. The CNP SNP did not contribute to white matter volume variation in the diagnostic groups studied. Variation in the genes coding for structural and protective components of myelin are implicated in abnormal white matter volume in the emotion circuitry of the cingulum, fornix, parahippocampal gyrus and UF in psychotic disorders.

Revisiting Brain Atrophy and Its Relationship to Disability in Multiple Sclerosis

BackgroundBrain atrophy is a well-accepted imaging biomarker of multiple sclerosis (MS) that partially correlates with both physical disability and cognitive impairment.Methodology/Principal FindingsBased on MRI scans of 60 MS cases and 37 healthy volunteers, we measured the volumes of white matter (WM) lesions, cortical gray matter (GM), cerebral WM, caudate nucleus, putamen, thalamus, ventricles, and brainstem using a validated and completely automated segmentation method. We correlated these volumes with the Expanded Disability Status Scale (EDSS), MS Severity Scale (MSSS), MS Functional Composite (MSFC), and quantitative measures of ankle strength and toe sensation. Normalized volumes of both cortical and subcortical GM structures were abnormally low in the MS group, whereas no abnormality was found in the volume of the cerebral WM. High physical disability was associated with low cerebral WM, thalamus, and brainstem volumes (partial correlation coefficients ∼0.3–0.4) but not with low cortical GM volume. Thalamus volumes were inversely correlated with lesion load (r = −0.36, p<0.005).ConclusionThe GM is atrophic in MS. Although lower WM volume is associated with greater disability, as might be expected, WM volume was on average in the normal range. This paradoxical result might be explained by the presence of coexisting pathological processes, such as tissue damage and repair, that cause both atrophy and hypertrophy and that underlie the observed disability.

Trait impulsivity and prefrontal gray matter reductions in cocaine dependent individuals

BackgroundImpulsivity is thought to play a key role in cocaine addiction onset and progression; therefore, we hypothesized that different facets of impulsive personality may be significantly associated with brain structural abnormalities in cocaine-dependent individuals. MethodsThirty-eight cocaine-dependent individuals and 38 non-drug using controls completed the UPPS-P scale (measuring five different facets of impulsivity: sensation seeking, lack of premeditation, lack of perseverance, and positive and negative urgency) and were scanned on a 3T MRI scanner. We used whole-brain voxel-based morphometry analyses (VBM) to detect differences in gray matter (GM) and white matter (WM) volumes between cocaine users and controls, and to measure differences in the way that impulsivity relates to GM and WM volumes in cocaine users vs. controls. ResultsCocaine-dependent individuals had lower GM volumes in a number of sections of the orbitofrontal cortex, right inferior frontal gyrus, right insula, left amygdala and parahippocampal gyrus, temporal gyrus, and bilateral caudate. They also had lower WM volumes in the left inferior and medial frontal gyrus, superior temporal gyrus, right anterior cingulate cortex, insula and caudate. There was a positive correlation between trait impulsivity and GM volume in the left inferior/middle frontal gyrus of cocaine-dependent individuals, a pattern directly opposed to the association in controls. Conversely, in cocaine users lack of premeditation was negatively correlated with GM volume in the insula and the putamen. ConclusionsTrait impulsivity may influence cocaine dependence by impacting its neurobiological underpinnings in frontostriatal systems.

The neuroanatomy of genetic subtype differences in Prader–Willi syndrome

Despite behavioral differences between genetic subtypes of Prader-Willi syndrome (PWS), no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of PWS [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)]. Fifteen individuals with PWS due to a typical deletion [(DEL) type I; n = 5, type II; n = 10], eight with PWS due to UPD, and 25 age-matched healthy-weight individuals (HWC) participated in structural magnetic resonance imaging (MRI) scans. A custom voxel-based morphometry processing stream was used to examine regional differences in gray and white matter volume (WMV) between groups, covarying for age, sex, and body mass index (BMI). Overall, compared to HWC, PWS individuals had lower gray matter volumes (GMV) that encompassed the prefrontal, orbitofrontal and temporal cortices, hippocampus and parahippocampal gyrus, and lower WMVs in the brain stem, cerebellum, medial temporal, and frontal cortex. Compared to UPD, the DEL subtypes had lower GMV primarily in the prefrontal and temporal cortices, and lower white matter in the parietal cortex. The UPD subtype had more extensive lower gray and WMVs in the orbitofrontal and limbic cortices compared to HWC. These preliminary findings are the first structural neuroimaging findings to support potentially separate neural mechanisms mediating the behavioral differences seen in these genetic subtypes.

Morphometric Differences in the Heschl's Gyrus of Hearing Impaired and Normal Hearing Infants

This study investigates the morphometry of Heschl's gyrus and its included primary auditory cortex (PAC) in hearing impaired (HI) and normal hearing (NH) infants. Fourty-two infants, age 8-19 months, with NH (n = 26) or hearing impairment (n = 16) were studied using high-resolution 3D magnetic resonance imaging. Gray matter (GM) and white matter (WM) volumes were obtained using software for automatic brain imaging segmentation to estimate the volume of each tissue within manually defined regions for the anterior portion of Heschl's gyrus (aHG) in each individual subject, transformed to an infant brain template space. Interactions among group (HI, NH), tissue type (GM, WM), and hemisphere (left, right) were examined using analysis of variance. Whole-brain voxel-based morphometry was utilized to explore volume differences between groups across the entire brain. The HI group showed increased GM and decreased WM in aHG compared with the NH group; likely effects of auditory deprivation. The HI group did not exhibit their typical L > R asymmetry pattern that the NH group showed. Increased GM in aHG in HI infants may represent abnormal cortical development in PAC as seen in animal models of sensory deprivation. Lower WM volume is consistent with studies with deaf adults.

Homocysteine, neural atrophy, and the effect of caloric restriction in rhesus monkeys

Higher serum homocysteine (Hcy) levels in humans are associated with vascular pathology and greater risk for dementia, as well as lower global and regional volumes in frontal lobe and hippocampus. Calorie restriction (CR) in rhesus monkeys (Macaca mulatta) may confer neural protection against age- or Hcy-related vascular pathology. Hcy was collected proximal to a magnetic resonance imaging (MRI) acquisition in aged rhesus monkeys and regressed against volumetric and diffusion tensor imaging indexes using voxel-wise analyses. Higher Hcy was associated with lower white matter volume in pons and corpus callosum. Hcy was correlated with lower gray matter volume and density in prefrontal cortices and striatum. CR did not influence Hcy levels. However, control monkeys exhibited a strong negative correlation between Hcy and global gray matter, whereas no relationship was evident for the CR monkeys. Similar group differences were also seen across modalities in the splenium of the corpus callosum, prefrontal cortices, hippocampus, and somatosensory areas. The data suggest that CR may ameliorate the influence of Hcy on several important age-related parameters of parenchymal health.

Coronary Artery Calcium, Brain Function and Structure

Several cardiovascular risk factors are associated with cognitive disorders in older persons. Little is known about the association of the burden of coronary atherosclerosis with brain structure and function. This is a cross-sectional analysis of data from the Age, Gene, Environment Susceptibility (AGES)-Reykjavik Study cohort of men and women born 1907 to 1935. Coronary artery calcification (CAC), a marker of atherosclerotic burden, was measured with CT. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. Dementia was assessed in a multistep procedure and diagnosed according to international guidelines. Quantitative data on total intracranial and tissue volumes (total, gray matter volume, white matter volume, and white matter lesion volume), cerebral infarcts, and cerebral microbleeds were obtained with brain MRI. The association of CAC with dementia (n=165 cases) and cognitive function in nondemented subjects (n=4085), and separately with MRI outcomes, was examined in multivariate models adjusting for demographic and vascular risk factors. Analyses tested whether brain structure mediated the associations of CAC to cognitive function. Subjects with higher CAC were more likely to have dementia and lower cognitive scores, more likely to have lower white matter volume, gray matter volume, and total brain tissue, and to have more cerebral infarcts, cerebral microbleeds, and white matter lesions. The relations of cognitive performance and dementia to CAC were significantly attenuated when the models were adjusted for brain lesions and volumes. In a population-based sample, increasing atherosclerotic load assessed by CAC is associated with poorer cognitive performance and dementia, and these relations are mediated by evidence of brain pathology.

Brain Volume and Survival from Age 78 to 85: The Contribution of Alzheimer‐Type Magnetic Resonance Imaging Findings

To test the prediction of survival using magnetic resonance imaging (MRI)-derived global and regional brain volumes in subjects aged 78 to 79 without dementia. Observational follow-up study. University teaching hospital. Participants born in 1921, recruited in 1997/98 to a longitudinal study, who underwent brain MRI in 1999/2000. Vital status on May 12, 2006, global and regional brain volumes. Thirty-seven of 98 (34.9%) participants died during follow-up. After adjustment for cognitive ability at time of MRI examination, childhood intelligence, sex, hypertension, smoking history, obesity, hyperlipidemia, and age at MRI, proportion of intracranial volume occupied by the brain (brain fraction) predicted death before age 85 (P=.04). Participants with brain fraction less than 0.726 had more than twice the relative risk (2.8, 95% confidence interval=1.1-7.3) of death than participants with brain fraction greater 0.726. Lower survival was significantly associated with lower gray matter volumes in bilateral parietal and left frontoparietal areas and with lower white matter volumes in left parietal and right posterior temporal regions. Cox regression analysis showed that parietal white matter volume (P=.003), a subsequent diagnosis of dementia (P<.001), and sex (P=.004) were independent predictors of survival. In participants aged 78 to 79, a lower global brain fraction predicted survival to approximately age 85. Smaller regional volumetric brain reductions, seen in Alzheimer's disease (AD), also predicted survival independent of dementia. The presence of prodromal AD probably explain the main findings.

Early imaging predicts later cognitive impairment in primary progressive multiple sclerosis

Cognitive impairment in primary progressive multiple sclerosis (PPMS) is common and correlates modestly with contemporary lesion burden and brain volume. Using a cohort/case control methodology, we explore the ability of MRI abnormalities, including those in the normal-appearing brain tissue, to predict future cognitive dysfunction in PPMS. Thirty-one patients recruited into a longitudinal study within 5 years of onset of PPMS were assessed neuropsychologically on average 5.5 years later along with 31 matched healthy controls. MRI data obtained at entry into the study (lesion metrics, brain volumes, magnetization transfer ratio histogram metrics, and magnetic resonance spectroscopy metabolite concentrations) were used to predict cognitive impairment at follow-up. Twenty-nine percent of patients were categorized as cognitively impaired. T2 lesion volume was the best MRI predictor of overall cognitive function and performance on tests of verbal memory and attention/speed of information processing. Low gray matter magnetization transfer ratio was the best predictor of poor performance on a further test of attention/speed of information processing and an executive function test. Low gray and white matter volumes were independent predictors of poor performance on a second test of executive function. MRI abnormalities observed in early primary progressive multiple sclerosis can predict cognitive impairment 5 years later. While focal damage disrupting white matter tracts appears to be the most important predictor of subsequent cognitive dysfunction, gray matter pathology also plays a role.

Evaluation of Older Persons with Mild Cognitive Deficits: Potential Utility of Magnetic Resonance Imaging

This study evaluated brain volumes in healthy older subjects without dementia who presented with memory complaints. The objective was to examine cortical volumes in relation to cognitive performance among patients who do not have dementia, but who do have mild cognitive deficits. Fifteen participants were evaluated (mean age = 71.8 +/- 6.2). Brain structure was measured via high-resolution magnetic resonance imaging to quantify gray and white matter volumes. Volumetric measures were assessed relative to cognitive function in separate regression models controlling for total cerebral volume. Reported here are measures of global cognitive performance using the Mattis Dementia Rating Scale (DRS) in relation to volumetric measures. Baseline MMSE scores ranged from 27 to 30 (mean = 29.3; SD = 0.9). After controlling for total cerebral volume, we observed that lower white matter volume in the temporal lobe [F(1,14) = 5.72, p = 0.03] was associated with lower performance on the Mattis Dementia Rating Scale (DRS). Structural imaging may help provide useful clinical information in the context of mild cognitive decline. Currently, the diagnosis of dementia relies on longitudinal measures of cognition. Future studies will help determine whether the addition of brain imaging may enhance diagnostic certainty as well as predict long-term outcome.

Lower White-Matter Volumes in Men with Pedophilia

Sexual interest in children has been associated with adverse life experiences, such as childhood trauma and abuse. However, neuropsychological findings

Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults

In the present study, we investigated age-related changes in interactions between efficiency of neuronal repair mechanisms and efficiency of cholinergic neurotransmission in the context of attentional orienting. In addition, we explored white matter volume changes as possible neuronal underpinnings. A sample of 230 healthy middle-aged (53-64 years) and older (65-75 years) adults was genotyped for polymorphisms of APOE and CHRNA4, a nicotinic receptor subunit gene. Participants were administered a visuospatial attention task involving letter discrimination with location cues of varying validity. Genotype effects on white matter volume were also investigated in a subset of participants who received MRI scans. APOE interacted with CHRNA4, such that APOE-epsilon4 carriers who were also CHRNA4 TT homozygotes showed disproportionately slowed reaction time (RT) following invalid location cues. The interaction was stronger in the middle-aged participants than in the older participants. There was also a trend for individuals with combined APOE-epsilon4/CHRNA4 TT genotypes to show both lower white matter volume and slower overall RT on the attention task The interaction of a neurotransmission gene (CHRNA4) and a susceptibility gene (APOE) suggests that the efficiency of neuronal repair mechanisms may modulate the cholinergic system to influence attentional function.