Patients with Parkinson's disease and a history of falls have decreased cerebellar grey matter volumes in the cognitive cerebellum

The objective of this study was to determine if cerebellar gray matter (GM) structure differs between fallers and non-fallers with Parkinson's disease (PD) and their respective association to cognitive function. A total of 48 fallers and 63 non-fallers with PD were identified from the Parkinson's Progression Markers Initiative database. Fallers were categorized as those who self-reported a fall within the past year. Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Montreal Cognitive Assessment (MoCA), Trail Making Test parts A (TMT-A) and B (TMT-B) scores were collected for each patient. Cerebellar GM volumes were derived from magnetic resonance imaging data. Analyses of covariance were used to compare group differences. Partial Pearson's correlations were used to assess the relationship between cerebellar GM volumes to UPDRS-III and cognitive outcomes. Significance was set at P ≤ 0.01. Fallers had significantly decreased GM volumes in lobules V, Crus-1, Crus-2, and VIIb (P < 0.01). Cerebellar GM volumes in non-fallers demonstrated little-to-no relationship with UPDRS-III, MoCA, and TMT-B (P > 0.01). However, TMT-A performance demonstrated significant, fair association to GM volumes in lobules I–IV, V, VI, Crus-1, and Crus-2 (r = ?0.44 – ?0.34, P < 0.01) in non-fallers. Patients with PD and a history of falls have significantly decreased GM volumes in cerebellar lobules associated with cognitive functions. However, these lobule volumes become disassociated with cognitive function compared to non-fallers.     

Infratentorial gray matter atrophy and excess in primary craniocervical dystonia

BackgroundPrimary craniocervical dystonia (CCD) is generally attributed to functional abnormalities in the cortico–striato–pallido–thalamocortical loops, but cerebellar pathways have also been implicated in neuroimaging studies. Hence, our purpose was to perform a volumetric evaluation of the infratentorial structures in CCD.MethodsWe compared 35 DYT1/DYT6 negative patients with CCD and 35 healthy controls. Cerebellar volume was evaluated using manual volumetry (DISPLAY software) and infratentorial volume by voxel based morphometry of gray matter (GM) segments derived from T1 weighted 3 T MRI using the SUIT tool (SPM8/Dartel). We used t-tests to compare infratentorial volumes between groups.ResultsCerebellar volume was (1.14 ± 0.17) × 10² cm³ for controls and (1.13 ± 0.14) × 10² cm³ for patients; p = 0.74. VBM demonstrated GM increase in the left I–IV cerebellar lobules and GM decrease in the left lobules VI and Crus I and in the right lobules VI, Crus I and VIIIb. In a secondary analysis, VBM demonstrated GM increase also in the brainstem, mostly in the pons.ConclusionWhile gray matter increase is observed in the anterior lobe of the cerebellum and in the brainstem, the atrophy is concentrated in the posterior lobe of the cerebellum, demonstrating a differential pattern of infratentorial involvement in CCD. This study shows subtle structural abnormalities of the cerebellum and brainstem in primary CCD.     

Meta-analytic investigations of common and distinct grey matter alterations in youths and adults with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a disabling illness with onset generally in childhood. OCD-youths differ from OCD-adults with regard to gender distribution, comorbidity patterns and treatment options. However, little is known about the neural correlate differences underpin those two populations. The current meta-analysis summarizes voxel based morphometry findings to elucidate whether differences of neural correlates exist between these two populations. Both OCD-youths and OCD-adults demonstrated greater striatal volume and smaller prefrontal grey matter volume (GMV). However, smaller GMV in left visual cortex was observed in OCD-youths only, while smaller GMV in anterior cingulate gyrus and greater GMV in cerebellum were demonstrated only in OCD-adults. Meta-regression showed greater GMV in left putamen was most prominent in samples with higher percentages of medicated OCD-adults. Our findings confirmed the most consistent GMV alterations in OCD were in prefrontal-striatal circuitry. Besides, other regions may involve at different developmental stages including deficits of visual cortex in OCD-youths and abnormalities of limbic-cerebellar circuit in OCD-adults. Medication effect may be more pronounced in the striatum, especially the putamen.     

Reversed hierarchy in the brain for general and specific cognitive abilities: A morphometric analysis

Intelligence is composed of a set of cognitive abilities hierarchically organized. General and specific abilities capture distinguishable, but related, facets of the intelligence construct. Here, we analyze gray matter with three morphometric indices (volume, cortical surface area, and cortical thickness) at three levels of the intelligence hierarchy (tests, first‐order factors, and a higher‐order general factor, g). A group of one hundred and four healthy young adults completed a cognitive battery and underwent high‐resolution structural MRI. Latent scores were computed for the intelligence factors and tests were also analyzed. The key finding reveals substantial variability in gray matter correlates at the test level, which is substantially reduced for the first‐order and the higher‐order factors. This supports a reversed hierarchy in the brain with respect to cognitive abilities at different psychometric levels: the greater the generality, the smaller the number of relevant gray matter clusters accounting for individual differences in intelligent performance. Hum Brain Mapp 35:3805–3818, 2014. © 2014 Wiley Periodicals, Inc .     

Moving forward: Age effects on the cerebellum underlie cognitive and motor declines

Though the cortical contributions to age-related declines in motor and cognitive performance are well-known, the potential contributions of the cerebellum are less clear. The diverse functions of the cerebellum make it an important structure to investigate in aging. Here, we review the extant literature on this topic. To date, there is evidence to indicate that there are morphological age differences in the cerebellum that are linked to motor and cognitive behavior. Cerebellar morphology is often as good as – or even better – at predicting performance than the prefrontal cortex. We also touch on the few studies using functional neuroimaging and connectivity analyses that further implicate the cerebellum in age-related performance declines. Importantly, we provide a conceptual framework for the cerebellum influencing age differences in performance, centered on the notion of degraded internal models. The evidence indicating that cerebellar age differences associate with performance highlights the need for additional work in this domain to further elucidate the role of the cerebellum in age differences in movement control and cognitive function.     

The effect of damage to the cerebellum on sensorimotor and cognitive function in children and adolescents

This review provides a developmental perspective on our current understanding of the role of the cerebellum for sensorimotor and cognitive function. A synopsis on the contribution of the cerebellum on motor control, learning and cognition based on experiments in human adults and animals is presented. This knowledge is contrasted to the relevant literature on children and adolescents. Special attention is given to findings derived from lesion studies and clinical reports that examined the effect of cerebellar damage during development. In general, it is established that children may show the same sensorimotor deficits as adults as a result of cerebellar damage, while the findings of cognitive dysfunction in children are less clear and remain controversial. Younger children do not necessarily recover better than older children or adolescents. The sparing of the deep cerebellar nuclei and the extent of adjuvant chemo- or radiation therapy are better predictors of later motor and cognitive function in children and adolescents.     

Genetic variants in the ErbB4 gene are associated with white matter integrity

Variations in the signalling NRG1-ErbB4 pathway have been associated with genetic susceptibility for both bipolar disorder and schizophrenia, although the underlying neural mechanisms are still uncertain. Reduced integrity of the anterior limb of the internal capsule (ALIC) has been found in association with risk-associated genetic variation in the 5′ region of the NRG1 gene. We hypothesised that variation in the gene encoding the NRG1 receptor, ErbB4, would also be associated with reduced ALIC integrity and with cognitive impairments characteristic of individuals with bipolar disorder and schizophrenia. Using diffusion tensor imaging (DTI), we examined the white matter integrity associations of the ErbB4 polymorphism rs4673628, which resides within intron 12 of the gene encoding ErbB4, in 36 healthy individuals. We also sought to clarify the cognitive effects of any findings. We found that genetic variation at the rs4673628 locus in the ErbB4 gene was significantly associated with ALIC white matter integrity which was also significantly and positively associated with mnemonic function. These findings provide further evidence to support a key role of NRG1-ErbB4 signalling in the pathophysiology of major mental disorders.     

Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: An in vivo study with TBSS and VBM

We investigated the relationship between the damage occurring in the brain normal‐appearing white matter (NAWM) and in the gray matter (GM) in patients with early Primary Progressive multiple sclerosis (PPMS), using Tract‐Based Spatial Statistics (TBSS) and an optimized voxel‐based morphometry (VBM) approach. Thirty‐five patients with early PPMS underwent diffusion tensor and conventional imaging and were clinically assessed. TBSS and VBM were employed to localize regions of lower fractional anisotropy (FA) and lower GM volume in patients compared with controls. Areas of anatomical and quantitative correlation between NAWM and GM damage were detected. Multiple regression analyses were performed to investigate whether NAWM FA or GM volume of regions correlated with clinical scores independently from the other and from age and gender. In patients, we found 11 brain regions that showed an anatomical correspondence between reduced NAWM FA and GM atrophy; of these, four showed a quantitative correlation (i.e., the right sensory motor region with the adjacent corticospinal tract, the left and right thalamus with the corresponding thalamic radiations and the left insula with the adjacent WM). Either the NAWM FA or the GM volume in each of these regions correlated with disability. These results demonstrate a link between the pathological processes occurring in the NAWM and in the GM in PPMS in specific, clinically relevant brain areas. Longitudinal studies will determine whether the GM atrophy precedes or follows the NAWM damage. The methodology that we described may be useful to investigate other neurological disorders affecting both the WM and the GM. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Group‐specific regional white matter abnormality revealed in diffusion tensor imaging of medial temporal lobe epilepsy without hippocampal sclerosis

Purpose: In comparison to temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (TLE‐HS), TLE patients without HS (TLE‐NH) have a similar clinical course but may result in worse surgical outcome. We investigated whether the clinical features related to the lack of HS in TLE patients (TLE‐NH) can be explained by water diffusion abnormalities throughout diffusion tensor imaging (DTI) by voxel‐based analysis. Methods: Nineteen patients with TLE‐HS (left/right TLE 12:7), 18 patients with TLE‐NH (left/right TLE 10:8), and 20 controls were included in the study. By statistical parametric mapping (SPM2), the diffusion properties specific to disease characteristics (TLE‐HS vs. TLE‐NH) were analyzed. Results: In TLE‐HS, we found the areas of increased mean diffusivity (MD) in their ipsilateral temporal and extratemporal areas including the hippocampus, parahippocampal, and frontoparietal regions. Left TLE‐HS showed a characteristic MD increase in the ipsilateral posterior cingulum, isthmus of corpus callosum, and contralateral occipital and temporal regions, which was not observed in right TLE‐HS group. In left TLE‐NH, two regions of increased MD were observed in the ipsilateral posterior fornix (within fusiform gyrus) and posterior cingulum. Right TLE‐NH did not show any increased MD. Discussion: In left TLE‐NH, we could find the water diffusion change along the posterior cingulum, which was quite different from the extensive abnormality from TLE‐HS. In addition, there was a lesion‐side–specific distribution (left predominant) of pathology in mesial TLE. This provides a possibility that TLE‐NH is a heterogenous or entity different from TLE‐HS.     

阿尔茨海默病患者脑白质损害与认知功能的关系

目的用磁共振扩散张量成像(DTI)研究阿尔茨海默病(AD)患者脑白质损害的特点及其与认知功能改变的相关性。方法对16例AD患者和12名年龄及性别相当的健康老年人行DTI、T1液体衰减反转恢复序列(FLAIR)及T2-FLAIR检查,测量胼胝体膝部和压部、内囊前肢和后肢、额颞顶枕叶白质的部分各向异性分数值(FA)和平均弥散度(MD),分析FA、MD值与简易精神状态量表(MMSE)评分之间的相关关系。结果AD患者胼胝体压部、额叶、顶叶、颞叶FA值分别为0.602±0.043、0.270±0.034、0.294±0.043、0.302±0.032,与健康老人组相比显著下降(P<0.05),且与MMSE评分呈正相关关系,而内囊前后肢、枕叶、胼胝体膝部的FA值则无明显变化(P>0.05);胼胝体压部、顶叶白质的MD值分别为(0.918±0.029)、(0.826±0.015)×10-9m2/s,与健康老人组相比显著升高(P<0.01),且与MMSE评分呈负相关,而内囊前后肢、额叶、颞叶、枕叶和胼胝体膝部的MD值则无明显变化(P>0.05)。结论AD患者表现为脑白质的选择性损害,且损害程度与认知功能密切相关;这种选择性损害反映了AD病理机制中皮质-皮质及皮质-皮质下联系的丢失;DTI技术可以用来监测疾病的进展情况及评价AD治疗药物的临床疗效。     

Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients.

BACKGROUND: Structural deficiencies within limbic and prefrontal regions may contribute to the characteristic drug-seeking and drug-taking behaviors that prevail in persons dependent on cocaine. To date, a focal structural analysis of the brains of cocaine patients has not been undertaken. METHODS: We used voxel based morphometry in conjunction with statistical parametric mapping on the structural magnetic resonance images of cocaine-dependent (n = 13) and cocaine-naive individuals (n = 16) to assess differences between the two groups in gray and white matter concentration. RESULTS: We report a decrease in gray matter concentration in the ventromedial orbitofrontal, anterior cingulate, anteroventral insular, and superior temporal cortices of cocaine patients in comparison to controls (p <.01 corrected for multiple comparisons). The average percentage decrease in gray matter concentration within a region ranged from 5% to 11%. White matter concentration did not differ between groups. CONCLUSIONS: We conclude that the brains of cocaine patients are structurally dissimilar from those of nondrug-using controls. The differences were detected in regions involved in decision-making, behavioral inhibition and assignation of emotional valence to environmental stimuli and, hence, may contribute to some of the behavioral deficits characteristic of chronic cocaine users.     

早期帕金森病患者非运动症状与脑结构异常的观察

目的 分析早期帕金森病(PD)患者非运动症状(NMS)的特点及相关脑灰质结构异常.方法 对34例早期原发性PD患者的NMS数量进行记录,并与年龄、病程、病情严重程度及帕金森病统一评价量表(UPDRSⅢ评分)等进行相关分析.应用3D-T1WI脑容积扫描序列对PD患者与25名健康对照进行扫描,采用基于体素的形态学测量(VBM)方法进行数据处理得到全脑灰质图像.结果 PD组患者NMS数量显著高于对照组,且与年龄、病程及MoCA评分无相关性;与UPDRSⅢ评分、H-Y分期呈正相关;与MMSE呈负相关.PD组患者双侧额叶中下回、双侧岛叶、右侧颞中回、右侧楔叶、舌回;左侧颞上回、颞横回灰质不同程度萎缩,双侧额叶萎缩与NMS评分呈正相关.结论 NMS可在早期PD患者中出现,提示PD是累及多系统的神经系统变性病,且PD患者的NMS数量与脑灰质体积缺失关系密切.     

Sleep electroencephalography and brain maturation: developmental trajectories and the relation with cognitive functioning

Sleep has a crucial role in brain functioning and cognition, and several sleep electroencephalography (EEG) hallmarks are associated with intellectual abilities, neural plasticity, and learning processes. Starting from this evidence, a growing interest has been raised regarding the involvement of the sleep EEG in brain maturation and cognitive functioning during typical development (TD). The aim of this review is to provide a general framework about the maturational changes and the functional role of the human sleep EEG during TD from birth to late adolescence (≤22 years). The reviewed findings show large developmental modifications in several sleep EEG hallmarks (slow wave activity, sleep spindles, theta activity, and cyclic alternating pattern) during TD, and many studies support the notion of an active role of sleep slow wave activity in supporting brain maturation. Moreover, we focus on the possible relation between sleep microstructure, intelligence, and several memory domains (declarative, emotional, procedural), showing that sleep EEG oscillations seem involved in intellectual abilities and learning processes during TD, although results are often conflicting and divergent from findings in adults. Starting from the present literature, we propose that larger methodological uniformity, greater attention to the topographical and maturational aspects of the sleep EEG oscillations and their mutual interactions, and a higher number of longitudinal studies will be essential to clarify the role of the sleep EEG in cognitive functioning during TD.     

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.
Methods:  We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls.
Results:  Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices.
Discussion:  We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.     

Early cortical gray matter loss and cognitive correlates in non-demented Parkinson's patients

BackgroundWhereas the motor dysfunction in Parkinson's disease (PD) has been related to deficits in basal ganglia (BG) structures, neural correlates of cognitive changes remain to be fully defined. This study tested the hypothesis that cognitive changes in non-demented PD may be related to cortical gray matter (GM) loss.MethodsHigh-resolution T1-weighted magnetic resonance images of the brain and comprehensive cognitive function tests were acquired in 40 right-handed, non-demented PD subjects and 40 matched controls. GM changes were assessed using voxel-based morphometry (VBM) in FSL. VBM and cognitive results were compared between PD and controls, and correlation analyses were performed between those brain areas and cognitive domains that showed significant group differences.ResultsPD patients demonstrated significant GM reduction localized predominantly in frontal and parieto-occipital regions. Patients also showed reduced performance in fine motor speed and set-shifting compared to controls. Fine motor speed and set-shifting were associated with GM volume in the frontal cortex in controls, whereas these domains were associated primarily with occipital GM regions in PD patients.ConclusionsNon-demented PD subjects demonstrate cortical structural changes in frontal and parieto-occipital regions compared to controls. The association between typically recognized “frontal lobe” function and occipital lobe volume suggested a compensatory role of occipital lobe to primary fronto-striatal pathology in PD. Further longitudinal study of these changing structure–function relationships is needed to understand the neural bases of symptom progression in PD.