Cerebellar Gray Matter Volume Research Articles

Morphological changes of cerebellar substructures in temporal lobe epilepsy: A complex phenomenon, not mere atrophy

PurposeTo evaluate cerebellar volume changes in temporal lobe epilepsy (TLE) patients in greater detail. We aimed to determine which discrete substructures significantly differ in patients with TLE compared to controls and the nature of this difference. Correlations with age at epilepsy onset, epilepsy duration, seizure frequency, and total number of antiepileptic drugs (AED) in the patient’s history were studied. We analyzed the potential association between cerebellar atrophy and epilepsy surgery outcome. MethodsStudy participants were 36 TLE patients; 22 hippocampal sclerosis (HS) only and 38 healthy controls. All patients later underwent temporal lobe resection. All subjects were examined using 1.5T MRI. Cerebellar volume was adjusted for total intracranial volume, age, and gender, and measured using voxel-based morphometry. Cerebellar substructures were defined using the AAL atlas. Data processing was performed automatically. Separate analyses for HS only subset were performed. ResultsTotal cerebellar gray matter volume (GMV) appeared non-significantly smaller in epilepsy patients. Within the substructures, the GMV of the selected vermian segments were significantly larger in patients. The GMV of the whole cerebellum and of all individual cerebellar substructures non-significantly decreased with increasing complex partial seizure frequency and total number of AEDs in the patient’s history. Total cerebellar GMV was significantly smaller in patients with persistent seizures after epilepsy surgery than in seizure-free patients. ConclusionCerebellar atrophy is a complex phenomenon, the character of changes differs significantly within the cerebellar substructures.Total cerebellar GMV reduction is associated with worse outcome of temporal lobe resection.

Lobular patterns of cerebellar resting-state connectivity in adults with Autism Spectrum Disorder.

Autism spectrum disorder is a neurodevelopmental disorder characterized by core deficits in social functioning. Core autistics traits refer to poor social and imagination skills, poor attention-switching/strong focus of attention, exceptional attention to detail, as expressed by the autism-spectrum quotient. Over the years, the importance of the cerebellum in the aetiology of autism spectrum disorder has been acknowledged. Neuroimaging studies have provided a strong support to this view, showing both structural and functional connectivity alterations to affect the cerebellum in autism spectrum disorder. According to the underconnectivity theory, disrupted connectivity within cerebello-cerebral networks has been specifically implicated in the aetiology of autism spectrum disorder. However, inconsistent results have been generated across studies. In this study, an integrated approach has been used in a selected population of adults with autism spectrum disorder to analyse both cerebellar morphometry and functional connectivity. In individuals with autism spectrum disorder, a decreased cerebellar grey matter volume affected the right Crus II, a region showing extensive connections with cerebral areas related to social functions. This grey matter reduction correlates with the degree of autistic traits as measured by autism-spectrum quotient. Interestingly, altered functional connectivity was found between the reduced cerebellar Crus II and contralateral cerebral regions, such as frontal and temporal areas. Overall, the present data suggest that adults with autism spectrum disorder present with specific cerebellar structural alterations that may affect functional connectivity within cerebello-cerebral modules relevant to social processing and account for core autistics traits.

Distinct cerebellar regions related to motor and cognitive performance in SCA6 patients

ObjectiveTo demonstrate a correlation between anatomic regional changes in Spinocerebellar Ataxia type 6 (SCA6) patients and measures of cognitive performance on neuropsychological tests. MethodsNeurocognitive testing was conducted on 24 SCA6 and 28 control subjects. For each cognitive test, SCA6 patients were compared against the controls using Student's t-test. For the cerebellar patients, using voxel based morphometry, correlations between cerebellar gray matter volume at each voxel and performance on the neuropsychological exams were calculated using the Pearson correlation coefficient implemented in SPM8. ResultsCompared to controls, SCA6 patients exhibited significantly impaired performance on the following cognitive tests: Rey-Auditory Verbal Learning Test Trial V, Controlled Oral Word Association phonemic test and semantic-verb test, Rey-Osterrieth Complex Figure copy test as well as immediate and delayed visuo-spatial memory recall test, Trail Making Test (TMT) Part A and Part B, Stroop Color Task completion time, Stroop Color-Word Task score, and Grooved Pegboard Test (GPT) Dominant and Non-Dominant Hand time. Correlations of gray matter density with cognitive test performance were determined for all SCA6 subjects. Using a p-value threshold of 0.001 and family-wise small volume error correction, significant correlations were found for GPT Non-Dominant, GPT Dominant, TMT Part A, and TMT Part B. ConclusionDifferent regional patterns of cerebellar involvement were found for the motoric GPT task and the executive version of the TMT. The results for the GPT strongly indicated that the integrity of medial superior hemispheric regions was associated with motor task performance, whereas executive cognitive function was localized in distinctly different inferior regions. This is the first VBM study to differentiate cognitive and motor contributions of the cerebellum.

Network-specific resting-state connectivity changes in the premotor-parietal axis in writer's cramp

BackgroundWriter's cramp is a task-specific dystonia impairing writing and sometimes other fine motor tasks. Neuroimaging studies using manifold designs have shown varying results regarding the nature of changes in the disease.ObjectiveTo clarify and extend the knowledge of underlying changes by investigating functional connectivity (FC) in intrinsic connectivity networks with putative sensorimotor function at rest in an increased number of study subjects.MethodsResting-state functional magnetic resonance imaging with independent component analysis was performed in 26/27 writer's cramp patients/healthy controls, and FC within and between resting state networks with putative sensorimotor function was compared. Additionally, voxel-based morphometry was carried out on the subjects' structural images.ResultsPatients displayed increased left- and reduced right-hemispheric primary sensorimotor FC in the premotor-parietal network. Mostly bilaterally altered dorsal/ventral premotor FC, as well as altered parietal FC were observed within multiple sensorimotor networks and showed differing network-dependent directionality. Beyond within-network FC changes and reduced right cerebellar grey matter volume in the structural analysis, the positive between-network FC of the cerebellar network and the basal ganglia network was reduced.ConclusionsAbnormal resting-state FC in multiple networks with putative sensorimotor function may act as basis of preexisting observations made during task-related neuroimaging. Further, altered connectivity between the cerebellar and basal ganglia network underlines the important role of these structures in the disease.

Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum

Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce. The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders. In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video-documented movement disorders was assessed. Voxel-based morphometry from high-resolution MRI was employed to compare cerebral and cerebellar gray matter volume between mitochondrial disease patients with and without movement disorders and healthy controls. Of the 50 (30%) patients with genetically confirmed mitochondrial disease, 15 presented with hypokinesia (parkinsonism 3/15), hyperkinesia (dystonia 5/15, myoclonus 3/15, chorea 2/15), and ataxia (3/15). In 3 patients, mitochondrial disease presented as adult-onset isolated dystonia. In comparison to healthy controls and mitochondrial disease patients without movement disorders, patients with hypo- and hyperkinetic movement disorders had significantly more cerebellar atrophy and an atrophy pattern predominantly involving cerebellar lobules VI and VII. This series provides clinical, genetic, volumetric imaging, and histologic data that indicate major involvement of the cerebellum in mitochondrial disease when it presents with hyper- and hypokinetic movement disorders. As a working hypothesis addressing the particular vulnerability of the cerebellum to energy deficiency, this adds substantially to the pathophysiological understanding of movement disorders in mitochondrial disease. Furthermore, it provides evidence that mitochondrial disease can present as adult-onset isolated dystonia. © 2017 International Parkinson and Movement Disorder Society.

P 3 Cerebellar gray matter volume decrease is associated with epileptic seizures in multiple sclerosis

Background Prevalence rates of epileptic seizures are three times higher in patients with multiple sclerosis (MS) compared to healthy controls ( van Munster et al., 2015 ). There is some evidence of gray matter (GM) as well as white matter (WM) lesions associated with epilepsy in MS ( van Munster et al., 2015 ). Here, we compared regional GM volume decrease using voxel based morphometry (VBM) to compare MS patients with and without epilepsy. Methods MRI images of 30 MS patients (15 with, 15 without epilepsy, matched due to disease duration, disease course, EDSS and age) were analyzed using voxel based morphometry. Second level analysis was done comparing regional GM volume in MS patients without compared to with epileptic seizures. Results MS-patients with epilepsy had regional GM volume decrease in the cerebellum compared to MS patients without epilepsy, mainly in the posterior lobe. Neither cerebral or deep GM structures revealed significant regional GM volume decrease. Discussion There is some evidence of hippocampal GM pathology associated with epilepsy ( Nicholas et al., 2016 ). In contrast, our VBM analyses did not reveal any association to cortical or subcortical GM volume decrease. Against our expectations, we found significant cerebellar GM volume decrease in the patients with, compared to without epileptic seizures. Interestingly, there is some evidence of cerebellar lesions generating seizures ( Foit et al., 2016 ), cerebellar abnormalities in idiopathic generalized epilepsy ( Li et al., 2010 ) as well as a cerebellar mediated, inhibitory effect on hippocampal seizures ( Krook-Magnuson et al., 2014 ). Our data has to be confirmed in larger samples, but at least are indicating a possible role of the cerebellum in MS patients with epilepsy.

129 Chronic Pain and Advanced MRI Techniques

Abstract INTRODUCTION Chronic Pain is a difficult entity to define and treat. The usual definition is that of pain that persists beyond expected healing period of 3–6 months. The pathophysiology, in particular changing neural connections, are still not widely agreed on. In recent years neuroimaging has shown evidence of structural reorganization and change. These new developments can further improve understanding of the brains plasticity and potentially new strategies to either help identify those experiencing acute pain at risk of transition to chronic pain, but also as a potential target for therapy. METHODS The study population of 67 patients includes: a group of 26 selected from a pain management service and a group of 41 normal controls. The participants were matched on age, gender and ethnicity. Each patient has undergone structural and diffusion-weighted MRI scans. Voxel based morphometry was used to investigate differences in grey matter volumes between the groups, as well as to investigate correlations with neurocognitive outcomes. Cortical thickness was also calculated. Tract-based spatial statistics (TBSS) were used to investigate differences and correlation with neurocognitive outcomes between diffusion metrics (fractional anisotropy, mean diffusivity). RESULTS >The chronic pain group showed smaller cerebellar grey matter volume relative to healthy controls. There was no difference in cortical thickness observed. Furthermore, those experiencing chronic pain exhibited significantly decreased FA and increased MD in multiple white matter tracts, relative to controls. CONCLUSION These findings suggest that cerebellar atrophy maybe involved in chronic pain.

Cerebellar Gray Matter Reductions Associate With Decreased Functional Connectivity in Nicotine-Dependent Individuals.

Nicotine dependence (ND) is a chronic, relapsing mental disorder characterized by compulsive cigarette seeking and smoking. Although the cerebellum plays an increasingly implicated role in ND, the exact cerebellar alterations in ND remain unclear. Identifying the localization of these cerebellar abnormalities in ND may help to further understand the role of the cerebellum in ND. Thus, we investigated the structural and functional alterations in the cerebellum in a large sample of smokers using the spatially unbiased infratentorial template (SUIT). High-resolution structural magnetic resonance imaging (MRI) data were acquired from 85 smokers and 41 nonsmokers. We applied voxel-based morphometry (VBM) and the SUIT cerebellar atlas to compare the cerebellar gray matter (GM) volume between smokers and nonsmokers. Using resting-state functional MRI data, we also performed seed-based functional connectivity (FC) analysis to examine the functional correlates of the GM volume changes. Both VBM and lobular analyses revealed smaller GM volume in the bilateral Crus I in smokers. The GM volume of the left Crus I was inversely correlated with the severity of nicotine dependence as assessed by Fagerström Test for Nicotine Dependence (r = -.268, p = .013). We also found reduced FC between the bilateral Crus I and brain regions involved in the default mode network and motor system, as well as the frontal and temporal cortex in smokers. Our results indicate that decreased cerebellar GM volume and corticocerebellar FC are associated with ND, and these may underlie the core ND phenotypes, including automatized smoking behavior, cognitive, and emotional deficits. As smoking remains a worldwide public health problem, identifying the related neural alterations may help to understand the pathophysiology of ND. Based on previous findings in the cerebellum, we investigated the localization of the GM differences and related FC changes in ND subjects. Our findings highlight altered corticocerebellar circuits in ND, suggesting an association between the cerebellum and the phenotypes of ND.

Cerebellar Contributions to Persistent Auditory Verbal Hallucinations in Patients with Schizophrenia.

There is growing evidence that the cerebellum plays a crucial role in the pathophysiology of schizophrenia symptoms. Despite increasing evidence for cerebellar involvement in affective, attentive, and cognitive functions including language processing and perception, investigations of cerebellar contributions to auditory verbal hallucinations (AVH) in schizophrenia are lacking. Using structural magnetic resonance imaging at 3T, we investigated the data of 20 patients with schizophrenia and 14 matched healthy controls. Ten patients were classified as having chronic and treatment resistant AVH (pAVH), whereas the remaining ten patients either never had AVH in the past or were in full remission with regard to AVH (nAVH). Employing cerebellum-optimized segmentation techniques, i.e., the Spatially Unbiased Infratentorial Template (SUIT) toolbox, we investigated cerebellar gray matter volume (GMV) differences among the pAVH, nAVH, and a healthy control group, the magnitude of their expression between these groups and the relationship between GMV and schizophrenia symptom load. Lower GMV in pAVH patients compared to controls was found in lobules VIIb and VIIIa. Additionally, lower GMV in pAVH compared to nAVH patients was found in lobule VIIIa. A negative relationship between VIIIa GMV and overall positive symptoms was detected. Correlations with AVH-specific psychometric scores were not significant. This study shows that there are structural changes in the cognitive regions of the cerebellum that are linked to a clinical phenotype presenting with persistent positive symptoms such as AVH. The results suggest that the cerebellum and its associated neural circuits do play a role in the emergence of positive symptoms in schizophrenia, but probably not exclusively in AVH symptom expression.

Impairments in Walking Ability, Dexterity, and Cognitive Function in Multiple Sclerosis Are Associated with Different Regional Cerebellar Gray Matter Loss.

Both histological and neuroimaging studies highlight the role of the cerebellum in multiple sclerosis (MS). There is at least some evidence for associations of cerebellar gray matter (GM) loss with motor and cognitive ability. We therefore correlated motor and cognitive ability scores (the multiple sclerosis functional composite MSFC) with regional cerebellar GM volumes. We used voxel-based morphometry (VBM) to assess the regional GM volume loss in a cohort of 45 MS patients. For the regression analysis, we used the clinical subscores of the multiple sclerosis functional composite (25-ft walk test (T25FW), nine-hole peg test (9HPT), paced auditory serial addition task (PASAT)). Decreased GM in distinct cerebellar areas was associated with different subscores of the MSFC in Larsell's lobule VI with the T25FW (t=5.16), in lobule IX with the 9HPT (t=3.95), and in lobule IX with the PASAT (t=4.81). Regional volume decrease in distinct cerebellar areas involved in motor and cognitive domains were associated with clinical impairment in these fields. Our data confirm the relationship between cerebellar GM volume loss and disability, extending the knowledge in the functional neuroanatomical perspective.

Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls.

Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=-0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.

Greater cerebellar gray matter volume in car drivers: an exploratory voxel-based morphometry study

Previous functional neuroimaging studies have identified multiple brain areas associated with distinct aspects of car driving in simulated traffic environments. Few studies, however, have examined brain morphology associated with everyday car-driving experience in real traffic. Thus, the aim of the current study was to identify gray matter volume differences between drivers and non-drivers. We collected T1-weighted structural brain images from 73 healthy young adults (36 drivers and 37 non-drivers). We performed a whole-brain voxel-based morphometry analysis to examine between-group differences in regional gray matter volume. Compared with non-drivers, drivers showed significantly greater gray matter volume in the left cerebellar hemisphere, which has been associated with cognitive rather than motor functioning. In contrast, we found no brain areas with significantly greater gray matter volume in non-drivers compared with drivers. Our findings indicate that experience with everyday car driving in real traffic is associated with greater gray matter volume in the left cerebellar hemisphere. This brain area may be involved in abilities that are critical for driving a car, but are not commonly or frequently used during other daily activities.

Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders.

Accumulating mental health research encourages a shift in focus towards transdiagnostic dimensional features that are shared across categorical disorders. In support of this shift, recent studies have identified a general liability factor for psychopathology – sometimes called the ‘p factor’ – that underlies shared risk for a wide range of mental disorders. Identifying neural correlates of this general liability would substantiate its importance in characterizing the shared origins of mental disorders and help us begin to understand the mechanisms through which the ‘p factor’ contributes to risk. Here we first replicate the ‘p factor’ using cross-sectional data from a volunteer sample of 1,246 university students, and then, using high-resolution multimodal structural neuroimaging, demonstrate that individuals with higher ‘p factor’ scores show reduced structural integrity of white matter pathways, as indexed by lower fractional anisotropy values, uniquely within the pons. Whole-brain analyses further revealed that higher ‘p factor’ scores are associated with reduced gray matter volume in the occipital lobe and left cerebellar lobule VIIb, which is functionally connected with prefrontal regions supporting cognitive control. Consistent with the preponderance of cerebellar afferents within the pons, we observed a significant positive correlation between the white matter integrity of the pons and cerebellar gray matter volume associated with higher ‘p factor’ scores. The results of our analyses provide initial evidence that structural alterations in cortico-cerebellar circuitry supporting core functions related to the basic integration, coordination, and monitoring of information may contribute to a general liability for common mental disorders.

Brain anatomy of symptom stratification in schizophrenia: A voxel based morphometry study

IntroductionAlthough some magnetic resonance imaging (MRI) studies have investigated the existence of a relationship between clinical severity and neuroanatomical alterations in patients with schizophrenia (SCZ), the biological signature associated with illness severity in schizophrenia is still uncertain.ObjectivesThis study aims to investigate structural brain abnormalities in SCZ with particular regards to the identification of potential deficits associated to the severity of illness.Methods1.5 T MRI data were acquired for 61 subjects with SCZ and 59 matched healthy controls (HC). The patient group was divided in two subgroups based on clinical severity, one composed by 34 mild-to-moderately ill patients and the other one by 27 severely ill patients, and compared with matched HC.ResultsThe whole group of patients with SCZ had significantly reduced gray matter (GM) volumes in left inferior and middle temporal gyrus compared to HC (P < 0.05, pFWE corrected). Furthermore, compared to HC, patients with mild-to-moderate illness showed decreased GM volumes in inferior temporal gyrus (P < 0.05, pFWE corrected) whereas those with severe illness had reduced right cerebellum (P < 0.05, cFWE corrected). No differences were observed between the two subgroups of patients.ConclusionsOur results showed significant GM volume reductions in left inferior and middle temporal gyrus in patients with SCZ compared to matched HC, confirming the role of this region in the pathophysiology of SCZ. Furthermore, we identified specific cerebellar gray matter volume reductions in patients with severe illness, which may contribute to stratify patients with SCZ according to their clinical phenotype expression, ultimately helping in guiding targeted therapeutic/rehabilitation interventions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Global brain atrophy and metabolic dysfunction in LGI1 encephalitis: A prospective multimodal MRI study

BackgroundChronic cognitive deficits are frequent in leucin-rich glioma-inactivated 1 protein (LGI1) encephalitis. We examined structural and metabolic brain abnormalities following LGI1 encephalitis and correlated findings with acute and follow-up clinical outcomes. MethodsNine patients underwent prospective multimodal 3 Tesla MRI 33.1±18months after disease onset, including automated volumetry, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Data were compared to 9 age- and sex-matched healthy controls. ResultsAlthough extratemporal lesions were not present on MRI in the acute stage, tract-based spatial statistics analyses of DTI during follow-up showed widespread changes in the cerebral and cerebellar white matter (WM), most prominent in the anterior parts of the corona radiata, capsula interna and corpus callosum. MRS revealed lower glutamine/glutamate WM levels compared to controls. Higher cerebellar gray matter volume was associated with better function at disease onset (measured by the modified Rankin Scale), and higher putaminal volume was associated with better cognition by Addenbrooke's Cognitive Examination test at 23.4±7.6months. ConclusionsPoor clinical outcome following LGI1 encephalitis is associated with global brain atrophy and disintegration of white matter tracts. The pathological changes affect not only temporomesial structures but also frontal lobes and the cerebellum.

Brain anatomy of symptom stratification in schizophrenia: a voxel-based morphometry study

Background: Although some Magnetic Resonance Imaging (MRI) studies have investigated the relationship between clinical severity and neuroanatomical alterations in patients with schizophrenia (SCZ), the biological signature associated with illness severity in schizophrenia is still uncertain. Therefore, this study aims to investigate structural brain abnormalities in SCZ, with particular regards to the identification of potential deficits associated with the severity of illness.Methods: In total, 1.5T MRI data were acquired for 61 subjects with SCZ and 59 matched healthy controls (HC). The patient group was divided in two sub-groups based on clinical severity, one composed of 34 mild-to-moderately ill patients, and the other of 27 severely ill patients, and compared with matched HC.Results: The whole group of patients with SCZ had significantly reduced grey matter (GM) volumes in the left inferior and middle temporal gyrus compared to HC (p < 0.05, pFWE corrected). Furthermore, compared to HC, patients with mild-to-moderate illness showed decreased GM volumes in the inferior and middle temporal gyrus, whereas those with severe illness had reduced GM volumes in the middle temporal gyrus and cerebellum bilaterally (all p < 0.001 uncorrected). No differences were observed between the two sub-groups of patients.Conclusion: The results showed significant GM volume reductions in temporal regions in patients with SCZ compared to matched HC, confirming the role of these regions in the pathophysiology of SCZ. Furthermore, specific cerebellar grey matter volume reductions were identified in patients with severe illness, which may contribute to stratifying patients with SCZ according to their clinical phenotype expression, ultimately helping in guiding targeted therapeutic/rehabilitation interventions.

Exploring the role of testosterone in the cerebellum link to neuroticism: From adolescence to early adulthood

Previous research has found an association between a smaller cerebellar volume and higher levels of neuroticism. The steroid hormone testosterone reduces stress responses and the susceptibility to negative mood. Together with in vitro studies showing a positive effect of testosterone on cerebellar gray matter volumes, we set out to explore the role of testosterone in the relation between cerebellar gray matter and neuroticism. Structural magnetic resonance imaging scans were acquired, and indices of neurotic personality traits were assessed by administering the depression and anxiety scale of the revised NEO personality inventory and Gray’s behavioural avoidance in one hundred and forty-nine healthy volunteers between 12 and 27 years of age. Results demonstrated an inverse relation between total brain corrected cerebellar volumes and neurotic personality traits in adolescents and young adults. In males, higher endogenous testosterone levels were associated with lower scores on neurotic personality traits and larger cerebellar gray matter volumes. No such relations were observed in the female participants. Analyses showed that testosterone significantly mediated the relation between male cerebellar gray matter and measures of neuroticism. Our findings on the interrelations between endogenous testosterone, neuroticism and cerebellar morphology provide a cerebellum-oriented framework for the susceptibility to experience negative emotions and mood in adolescence and early adulthood.

The obese brain as a heritable phenotype: a combined morphometry and twin study.

BackgroundBody weight and adiposity are heritable traits. To date it remains unknown whether obesity-associated brain structural alterations are under a similar level of genetic control.MethodsFor this study we utilized magnetic resonance imaging (MRI) data from the Human Connectome Project. Voxel based morphometry (VBM) was used to investigate associations between body mass index (BMI) and regional gray matter volume (GMV) in a sample of 875 young adults with a wide BMI range (386m/489f; age 28.8 ± 3.7y; BMI 26.6 ± 5.3 kg*m-2), that included 86 pairs of monozygotic twins and 82 pairs of dizygotic twins. Twin data were analyzed by applying the additive genetic, common environmental and residual effects (ACE) model to determine heritability of brain regions that were associated with BMI.ResultsWe observed positive associations between BMI and GMV in the ventromedial prefrontal cortex and the right cerebellum and widespread negative associations within the prefrontal cortex, cerebellum, temporal lobes and distinct subcortical structures. Varying degrees of heritability were found for BMI-associated brain regions, with highest heritability estimates for cerebellar GMV and subcortical structures.ConclusionsThese data indicate that brain regions associated with obesity are subject to differing levels of genetic control and environmental influences. Specific brain regions with high heritability might represent an inherent vulnerability factor for obesity.

Associations Between Cerebellar Subregional Morphometry and Alcoholism History in Men and Women.

Alcoholism has been linked to deficits in cognitive, behavioral, and emotional functions, and the cerebellum is important for optimal functioning of these abilities. However, little is known about how individual differences such as gender and drinking history might influence regional cerebellar abnormalities. Volumetric analyses of the cerebellum and its subregions were performed in relation to the interaction of gender and measures of drinking history. Structural magnetic resonance imaging scans of 44 alcoholic individuals (23 men) and 39 nonalcoholic controls (18 men) were obtained. In addition to measuring total cerebellar gray and white matter volumes, we measured 64 individual cerebellar parcellation units, as well as functionally defined a priori regions of interest that have been shown to correspond to functions impaired in alcoholism. Total cerebellar white matter volume was smaller in alcoholic relative to nonalcoholic participants. Moreover, volumes of parcellation units varied with drinking history, showing negative associations between years of heavy drinking and the anterior lobe, the vestibulocerebellar lobe, and the spinocerebellar subdivision. The negative association between anterior volume and years of heavy drinking was driven primarily by alcoholic men. Additionally, we observed larger white and gray matter volumes for alcoholic women than for alcoholic men. The identification of drinking-related abnormalities in cerebellar subregions lays a foundation that can be utilized to inform how cerebro-cerebellar networks are perturbed in this pathological condition. These results also provide estimates of how gender and individual differences in drinking history can predict cerebellar volumes.

Apolipoprotein E ε4 genotype status is not associated with neuroimaging outcomes in a large cohort of HIV+ individuals.

Previous neuroimaging studies suggest a negative relationship between the apolipoprotein (ApoE) ε4 allele and brain integrity in human immunodeficiency virus (HIV)-infected (HIV+) individuals, although the presence of this relationship across adulthood remains unclear. The purpose of this study is to clarify the discrepancies using a large, diverse group of HIV+ individuals and multiple imaging modalities sensitive to HIV. The association of ApoE ε4 with structural neuroimaging and magnetic resonance spectroscopy (MRS) was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Cortical and subcortical gray matter, abnormal and total white matter, ventricles, sulcal cerebrospinal fluid (CSF), and cerebellar gray matter, white matter, and CSF volumes, and MRS concentrations of myo-inositol, creatine, N-acetyl-aspartate, and choline in the frontal white matter (FWM), frontal gray matter (FGM), and basal ganglia were examined. Secondary analyses explored this relationship separately in individuals ≥50years old (n = 173) and <50years old (n = 63). No significant differences were observed between ApoE ε4+ (ApoE ε3/ε4 and ApoE ε4/ε4) individuals (n = 69) and ApoE ε4- (ApoE ε2/ε3 and ApoE ε3/ε3) individuals (n = 167). When individuals were further divided by age, no significant genotype group differences were identified in individuals <50 or ≥50years of age on any neuroimaging outcome. The ApoE ε4 allele did not affect brain integrity in this large, diverse sample of HIV+ individuals. The effects of ApoE ε4 may not be apparent until more advanced ages and may be more prominent when present along with other risk factors for neuronal damage.