Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.     

失独伴慢性创伤后应激障碍患者脑基于体素形态学及功能连接分析

目的:探讨失独伴慢性创伤后应激障碍（posttraumatic stress disorder, PTSD）患者脑灰质体积和功能连接改变及其与PTSD症状的关系。方法:2017年10月至2019年5月共纳入19例伴慢性PTSD失独者（伴PTSD组）、28例不伴PTSD失独者（不伴PTSD组）及27例健康对照者（对照组）...     

Altered brain function in persistent postural perceptual dizziness: A study on resting state functional connectivity

This study used resting state functional magnetic resonance imaging (rsfMRI) to investigate whole brain networks in patients with persistent postural perceptual dizziness (PPPD). We compared rsfMRI data from 38 patients with PPPD and 38 healthy controls using whole brain and region of interest analyses. We examined correlations among connectivity and clinical variables and tested the ability of a machine learning algorithm to classify subjects using rsfMRI results. Patients with PPPD showed: (a) increased connectivity of subcallosal cortex with left superior lateral occipital cortex and left middle frontal gyrus, (b) decreased connectivity of left hippocampus with bilateral central opercular cortices, left posterior opercular cortex, right insular cortex and cerebellum, and (c) decreased connectivity between right nucleus accumbens and anterior left temporal fusiform cortex. After controlling for anxiety and depression as covariates, patients with PPPD still showed decreased connectivity between left hippocampus and right inferior frontal gyrus, bilateral temporal lobes, bilateral insular cortices, bilateral central opercular cortex, left parietal opercular cortex, bilateral occipital lobes and cerebellum (bilateral lobules VI and V, and left I–IV). Dizziness handicap, anxiety, and depression correlated with connectivity in clinically meaningful brain regions. The machine learning algorithm correctly classified patients and controls with a sensitivity of 78.4%, specificity of 76.9%, and area under the curve = 0.88 using 11 connectivity parameters. Patients with PPPD showed reduced connectivity among the areas involved in multisensory vestibular processing and spatial cognition, but increased connectivity in networks linking visual and emotional processing. Connectivity patterns may become an imaging biomarker of PPPD.     

首次发病且未用药的成年早发和晚发抑郁症患者脑功能连接差异研究

目的比较成年早发抑郁症(EOD)和成年晚发抑郁症(LOD)患者默认网络(DMN)内部功能连接的差异,探究不同发病年龄的抑郁症患者是否有不同的发病机制。方法选取在昆明医科大学第一附属医院精神科门诊或住院的EOD患者(n=58)和LOD患者(n=62)为研究对象,同期招募年轻健康对照组(n=60)和年老健康对照组(n=52)。对受试者进行静息态功能磁共振扫描,选择左侧楔前叶为种子点,计算该种子点与全脑的功能连接,并比较各组间该种子点的功能连接差异。结果四组之间功能连接具有差异的脑区涉及双侧额叶、颞叶、基底节、枕叶、顶叶及小脑等脑区。EOD组左侧楔前叶与左侧小脑Crus1区、左侧小脑IX区、左侧颞中回、右侧楔前叶、右侧前扣带回、右侧额中回、右侧角回、右侧脑岛、右侧内侧额上回、右侧颞中回的功能连接均高于年轻健康对照组(Z=3. 752 4～5. 867 8,P均0. 05);而左侧楔前叶与左侧额中回、左侧中央旁小叶、右侧缘上回、右侧额上回、右侧颞下回、右侧中央后回、右侧中央前回、右侧枕上回的功能连接均低于年轻健康对照组(Z=-5. 007 6～-3. 797 7,P均0. 05)。LOD组左侧楔前叶与左侧小脑Crus2区、左侧尾状核、左侧颞下回、左侧小脑Crus1区、左侧角回、左侧额中回、右侧额中回、右侧角回、右侧眶额部额中回的功能连接均高于年老健康对照组(Z=4. 122 8～6. 579 4,P均0. 05);与左侧海马旁回、左侧额上回、右侧枕中回、右侧中央前回、右侧内侧额上回、右侧锯状回、右侧颞下回、右侧中央旁小叶、右侧梭状回、右侧后扣带回的功能连接均低于年老健康对照组(Z=-5. 884 0～-3. 617 2,P均0. 05)。EOD组左侧楔前叶与左侧锯状回、左侧小脑IV-VI区、左侧小脑Crus2区的功能连接比LOD组高(Z=4. 087 7、3. 937 4、3. 672 1,P均0. 05);EOD组左侧楔前叶与右侧额中回、右侧眶额部额下回、右侧额上回的功能连接比LOD组低(Z=-4. 274 8、-3. 956 8、-4. 724 3、-3. 663 2,P均0. 05)。结论 DMN内部功能连接增高及额顶网络功能连接降低可能与EOD的发病机制相关,而DMN前部功能连接增高和后部功能连接降低可能与LOD的发病机制相关,不同发病年龄的成年抑郁症患者可能有不同的发病机制。     

Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis

The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended cortical damage within the motor circuit of ALS patients. The functional changes in non-primary motor cortices pertaining to fronto-parietal circuit suggest an over-recruitment of a pre-existing physiological sensory-motor network. However, the concomitant fronto-parietal cortical atrophy arises the possibility that such a hyper-activation reflects cortical hyper-excitability due to loss of inhibitory inter-neurons.     

Structural brain and neuropsychometric changes associated with pediatric bipolar disorder with psychosis

James A, Hough M, James S, Burge L, Winmill L, Nijhawan S, Matthews PM, Zarei M. Structural brain and neuropsychometric changes associated with pediatric bipolar disorder with psychosis.
Bipolar Disord 2011: 13: 16–27. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: To identify neuropsychological and structural brain changes using a combination of high‐resolution structural and diffusion tensor imaging in pediatric bipolar disorder (PBD) with psychosis (presence of delusions and or hallucinations). Methods: We recruited 15 patients and 20 euthymic age‐ and gender‐matched healthy controls. All subjects underwent high‐resolution structural and diffusion tensor imaging. Voxel‐based morphometry (VBM), tract‐based spatial statistics (TBSS), and probabilistic tractography were used to analyse magnetic resonance imaging data. Results: The PBD subjects had normal overall intelligence with specific impairments in working memory, executive function, language function, and verbal memory. Reduced gray matter (GM) density was found in the left orbitofrontal cortex, left pars triangularis, right premotor cortex, occipital cortex, right occipital fusiform gyrus, and right crus of the cerebellum. TBSS analysis showed reduced fractional anisotropy (FA) in the anterior corpus callosum. Probabilistic tractography from this cluster showed that this region of the corpus callosum is connected with the prefrontal cortices, including those regions whose density is decreased in PBD. In addition, FA change was correlated with verbal memory and working memory, while more widespread reductions in GM density correlated with working memory, executive function, language function, and verbal memory. Conclusions: The findings suggest widespread cortical changes as well as specific involvement of interhemispheric prefrontal tracts in PBD, which may reflect delayed myelination in these tracts.     

Altered fMRI-derived functional connectivity in patients with high-tension glaucoma

BackgroundHigh-tension glaucoma (HTG) is associated with functional changes in the brain, and elevated intraocular pressure (IOP) is one of the major causes.PurposeTo evaluate the effects of high IOP on the brain in patients with HTG by using resting-state functional magnetic resonance imaging (rs-fMRI).Materials and methodsThirty-six patients with HTG and 20 age- and gender-matched healthy controls (HCs) were recruited and underwent IOP examination and rs-fMRI scan. Voxel-wise functional connectivity (FC) values were obtained between the Brodmann Area (BA) 17 (primary visual cortex) and the rest of the brain, two-sample t test was performed between HTG group and HCs. Correlation analysis was performed between FC and clinical information.ResultsCompared with HCs, HTG patients demonstrated decreased FC between BA 17 and the right precuneus gyrus, decreased FC between BA 17 and the right superior frontal gyrus (SFG) (GRF corrected at voxel level P < 0.001 and cluster level P < 0.05, two-tailed). FC between BA 17 and the right SFG showed significantly negative correlation with right eyes’ IOP and mean IOP.ConclusionHTG patients had abnormal FC changes between the visual cortex and multiple functional brain regions related to visual sense, memory consolidation and cognitive processing, which provided image support for the pathophysiology research of HTG, and revealed new targets for the accurate treatment of HTG.     

Duloxetine effects on striatal resting‐state functional connectivity in patients with major depressive disorder

Reward deficits and associated striatal circuitry disturbances have been implicated in the onset and progression of major depressive disorder (MDD). However, no studies have been conducted to investigate how the striatal circuitry changes during standard antidepressant, which is important for development of novel and targeted treatments for MDD. We examined the seed‐to‐whole‐brain functional connectivity (FC) for six striatal subregions based on resting‐state fMRI data of 23 MDD patients before and after 8‐week duloxetine, a serotonin, and noradrenaline reuptake inhibitor. Twenty‐three healthy controls (HCs) were also scanned twice with an 8‐week interval. After the analysis of covariance, we observed significant group‐by‐time interaction on FC of the dorsal caudate (DC), ventral striatum (VS), and putamen seeds. Post hoc analyses revealed that the FC between several right striatal seeds and left superior frontal gyrus (SFG), between right DC and left precuneus, between right superior VS and left inferior parietal lobe, were significantly higher in MDD patients compared to HCs at baseline and were reduced after treatment. Conversely, the FC between right inferior VS and left cerebellum was lower in MDD patients and was increased after treatment. Patients with larger reduction in right superior VS—left SFG FC exhibited larger alleviation of rumination. These findings suggest that duloxetine modulates the striatal FC with dorsolateral prefrontal cortex, posterior default mode network, and cerebellum, and partly, these changes underlie symptomatic improvement. This study adds to our understanding of antidepressant mechanism and future therapeutic development might benefit from considering these striatal circuitry as potential targets.     

Altered gray matter volume and functional connectivity in lung cancer patients with bone metastasis pain

Bone metastasis pain (BMP) is a severe chronic pain condition. Our previous studies on BMP revealed functional brain abnormalities. However, the potential effect of BMP on brain structure and function, especially gray matter volume (GMV) and related functional networks, have not yet been clearly illustrated. Voxel-based morphometry and functional connectivity (FC) analysis methods were used to investigate GMV and intrinsic FC differences in 45 right-handed lung cancer patients with BMP(+), 37 lung cancer patients without BMP(−), and 45 healthy controls (HCs). Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. Compared to HCs, BMP(+) group exhibited decreased GMV in medial frontal gyrus (MFG) and right middle temporal gyrus (MTG). Compared with BMP(−) group, BMP(+) group exhibited reduced GMV in cerebelum_6_L and left lingual gyrus. However, no regions with significant GMV differences were found between BMP(−) and HCs groups. Receiver operating characteristic analysis indicated the potential classification power of these aberrant regions. Correlation analysis revealed that GMV in the right MTG was positively associated with anxiety in BMP(+) group. Further FC analysis demonstrated enhanced interactions between MFG/right MTG and cerebellum in BMP(+) patients compared with HCs. These results showed that BMP was closely associated with cerebral alterations, which may induce the impairment of pain moderation circuit, deficits in cognitive function, dysfunction of emotional control, and sensorimotor processing. These findings may provide a fresh perspective and further neuroimaging evidence for the possible mechanisms of BMP. Furthermore, the role of the cerebellum in pain processing needs to be further investigated.     

Structural and functional brain alterations in anorexia nervosa:A multimodal meta‐analysis of neuroimaging studies

Anorexia nervosa (AN) is a complex psychiatric disorder with poorly understood etiology. Numerous voxel‐based morphometry (VBM) and resting‐state functional imaging studies have provided strong evidence of abnormal brain structure and intrinsic and functional activities in AN, but with inconsistent conclusions. Herein, a whole‐brain meta‐analysis was conducted on VBM (660 patients with AN, and 740 controls) and resting‐state functional imaging (425 patients with AN, and 461 controls) studies that measured differences in the gray matter volume (GMV) and intrinsic functional activity between patients with AN and healthy controls (HCs). Overall, patients with AN displayed decreased GMV in the bilateral median cingulate cortex (extending to the bilateral anterior and posterior cingulate cortex), and left middle occipital gyrus (extending to the left inferior parietal lobe). In resting‐state functional imaging studies, patients with AN displayed decreased resting‐state functional activity in the bilateral anterior cingulate cortex and bilateral median cingulate cortex, and increased resting‐state functional activity in the right parahippocampal gyrus. This multimodal meta‐analysis identified reductions of gray matter and functional activity in the anterior and median cingulate in patients with AN, which contributes to further understanding of the pathophysiology of AN.     

Altered resting-state network connectivity in panic disorder: an independent ComponentAnalysis

Panic disorder (PD) is a prevalent anxiety disorder but its neurobiology remains poorly understood. It has been proposed that the pathophysiology of PD is related to an abnormality in a particular neural network. However, most studies investigating resting-state functional connectivity (FC) have relied on a priori restrictions of seed regions, which may bias observations. This study investigated changes in intra and internetwork FC in the whole brain of patients with PD using resting-state functional magnetic resonance imaging. A voxel-wise data-driven independent component analysis was performed on 26 PD patients and 27 healthy controls (HCs).We compared the differences in the intra and internetwork FC between the two groups of subjects using statistical parametric mapping with two-sample t-tests. PD patients exhibited decreased intra-network FC in the right anterior cingulate cortex (ACC) of the anterior default mode network, the left precentral and postcentral gyrus of the sensorimotor network, the right lobule V/VI, the cerebellum vermis, and the left lobule VI of the cerebellum network compared with the HCs. The intra-network FC in the right ACC was negatively correlated with symptom severity. None of the pairs of resting state networks showed significant differences in functional network connectivity between the two groups. These results suggest that the brain networks associated with emotion regulation, interoceptive awareness, and fear and somatosensory processing may play an important role in the pathophysiology of PD.

     

Long-term changes in insula-mesolimbic structural and functional connectivity in obese patients after laparoscopic sleeve gastrectomy

Objective

Brain imaging studies have shown insula-related functional and structural abnormalities in patients with obesity. Laparoscopic sleeve gastrectomy is currently an effective procedure for treating obesity, which promotes acute recovery of brain functional and structural abnormalities in obese patients. The aim of this study was to investigate the long-term impact of laparoscopic sleeve gastrectomy on insula-related structural and functional connectivity.

Methods

Diffusion tensor imaging and resting-state functional magnetic resonance imaging were employed to investigate laparoscopic sleeve gastrectomy-induced changes in insula-related structural connectivity and corresponding resting-state functional connectivity in 25 obese patients prior to (PreLSG) and 12 months post-surgery (PostLSG₁₂).

Results

Results showed significant increases in fractional anisotropy and axial diffusivity between the right insula and anterior cingulate cortex, and higher fractional anisotropy of left insula-putamen, left insula-caudate and anterior cingulate cortex-right posterior cingulate cortex/precuneus at PostLSG12 compared with PreLSG. There were significant negative correlations between axial diffusivity of right insula-anterior cingulate cortex and body mass index, and fractional anisotropy of right insula-anterior cingulate cortex with scores on external eating at PostLSG12. Anxiety and depressive status ratings were negatively correlated with fractional anisotropy of left insula-putamen at PostLSG12. In addition, there was a significant decrease in resting-state functional connectivity between left insula and left caudate.

Conclusions

These findings demonstrate long-term changes in insula-related structural and functional connectivity abnormalities promoted by laparoscopic sleeve gastrectomy, which highlight its strong association with long-term weight loss and improvement in eating behaviors.

     

Disrupted functional connectivity of default mode and salience networks in chronic pancreatitis patients

ObjectiveThe functional connectivity of the brain in chronic pancreatitis (CP) remains unknown. This study aimed to investigate functional connectivity in CP patients using resting state functional magnetic resonance imaging (fMRI) and explore the associations to clinical parameters and altered cerebral metabolites.MethodsSeed-based and ROI-to-ROI analyses were performed to assess connectivity within and between the default mode network (DMN) and salience network (SN). Additionally, functional connectivity in these networks were investigated in relation to clinical parameters (CP etiology, pain, medication, etc.) and cerebral glutamate/creatine level in the anterior cingulate cortex.ResultsThirty CP patients and 23 healthy controls were analyzed. CP patients showed hyper-connectivity in DMN and SN as compared to healthy controls. Furthermore, CP patients had reduced anti-correlated functional connectivity between DMN and SN (all P ≤ 0.009). The altered DMN connectivity correlated to glutamate/creatine level (r = 0.503, P = 0.020) in patients with pain, but not to the clinical parameters.ConclusionsCP patients had altered functional connectivity within and between brain networks. Altered DMN functional connectivity had an association to cerebral metabolic changes.SignificanceAltered functional connectivity in CP share similarities with other chronic pain conditions, and support our understanding of altered brain circuitry associated with the CP disease.     

Regional Homogeneity Brain Alterations in Schizophrenia: An Activation Likelihood Estimation Meta-Analysis

ObjectiveResting state functional magnetic resonance imaging (rsfMRI) provides a lot of evidence for local abnormal brain activity in schizophrenia, but the results are not consistent. Our aim is to find out the consistent abnormal brain regions of the patients with schizophrenia by using regional homogeneity (ReHo), and indirectly understand the degree of brain damage of the patients with drug-naive first episode schizophrenia (Dn-FES) and chronic schizophrenia. MethodsWe performed the experiment by activation likelihood estimation (ALE) software to analysis the differences between people with schizophrenia group (all schizophrenia group and chronic schizophrenia group) and healthy controls. ResultsThirteen functional imaging studies were included in quantitative meta-analysis. All schizophrenia group showed decreased ReHo in bilateral precentral gyrus (PreCG) and left middle occipital gyrus (MOG), and increased ReHo in bilateral superior frontal gyrus (SFG) and right insula. Chronic schizophrenia group showed decreased ReHo in bilateral MOG, right fusiform gyrus, left PreCG, left cerebellum, right precuneus, left medial frontal gyrus and left anterior cingulate cortex (ACC). No significant increased brain areas were found in patients with chronic schizophrenia. ConclusionOur findings suggest that patients with chronic schizophrenia have more extensive brain damage than FES, which may contribute to our understanding of the progressive pathophysiology of schizophrenia.     

Voxel-based morphometry reveals extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism

ObjectivesTo determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients.DesignForty-three older PD patients (≥65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method.ResultsPatients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum.ConclusionsCortical and striatal atrophy were associated with dopamine non-responsive motor signs and cognitive impairment and provide a morphologic correlate for progression of PD. Cerebellar atrophy was found in older PD patients.     

Altered resting‐state functional connectivity within the developing social brain after pediatric traumatic brain injury

Traumatic brain injury (TBI) in childhood and adolescence can interrupt expected development, compromise the integrity of the social brain network (SBN) and impact social skills. Yet, no study has investigated functional alterations of the SBN following pediatric TBI. This study explored functional connectivity within the SBN following TBI in two independent adolescent samples. First, 14 adolescents with mild complex, moderate or severe TBI and 16 typically developing controls (TDC) underwent resting‐state functional magnetic resonance imaging 12–24 months post‐injury. Region of interest analyses were conducted to compare the groups' functional connectivity using selected SBN seeds. Then, replicative analysis was performed in an independent sample of adolescents with similar characteristics (9 TBI, 9 TDC). Results were adjusted for age, sex, socioeconomic status and total gray matter volume, and corrected for multiple comparisons. Significant between‐group differences were detected for functional connectivity in the dorsomedial prefrontal cortex and left fusiform gyrus, and between the left fusiform gyrus and left superior frontal gyrus, indicating positive functional connectivity for the TBI group (negative for TDC). The replication study revealed group differences in the same direction between the left superior frontal gyrus and right fusiform gyrus. This study indicates that pediatric TBI may alter functional connectivity of the social brain. Frontal‐fusiform connectivity has previously been shown to support affect recognition and changes in the function of this network could relate to more effortful processing and broad social impairments.     

Association between a longer duration of illness, age and lower frontal lobe grey matter volume in schizophrenia

The frontal lobe has an extended maturation period and may be vulnerable to the long-term effects of schizophrenia. We tested this hypothesis by studying the relationship between duration of illness (DoI), grey matter (GM) and cerebro-spinal fluid (CSF) volume across the whole brain. Sixty-four patients with schizophrenia and 25 healthy controls underwent structural MRI scanning and neuropsychological assessment. We performed regression analyses in patients to examine the relationship between DoI and GM and CSF volumes across the whole brain, and correlations in controls between age and GM or CSF volume of the regions where GM or CSF volumes were associated with DoI in patients. Correlations were also performed between GM volume in the regions associated with DoI and neuropsychological performance. A longer DoI was associated with lower GM volume in the left dorsomedial prefrontal cortex (PFC), right middle frontal cortex, left fusiform gyrus (FG) and left cerebellum (lobule III). Additionally, age was inversely associated with GM volume in the left dorsomedial PFC in patients, and in the left FG and CSF excess near the left cerebellum in healthy controls. Greater GM volume in the left dorsomedial PFC was associated with better working memory, attention and psychomotor speed in patients. Our findings suggest that the right middle frontal cortex is particularly vulnerable to the long-term effect of schizophrenia illness whereas the dorsomedial PFC, FG and cerebellum are affected by both a long DoI and aging. The effect of illness chronicity on GM volume in the left dorsomedial PFC may be extended to brain structure-neuropsychological function relationships.     

Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention‐deficit/hyperactivity disorder

Previous studies on working memory (WM) function in adults with attention‐deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls (n = 12) and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

The brain network reflecting bodily self-consciousness: a functional connectivity study

Several brain regions are important for processing self-location and first-person perspective, two important aspects of bodily self-consciousness. However, the interplay between these regions has not been clarified. In addition, while self-location and first-person perspective in healthy subjects are associated with bilateral activity in temporoparietal junction (TPJ), disturbed self-location and first-person perspective result from damage of only the right TPJ. Identifying the involved brain network and understanding the role of hemispheric specializations in encoding self-location and first-person perspective, will provide important information on system-level interactions neurally mediating bodily self-consciousness. Here, we used functional connectivity and showed that right and left TPJ are bilaterally connected to supplementary motor area, ventral premotor cortex, insula, intraparietal sulcus and occipitotemporal cortex. Furthermore, the functional connectivity between right TPJ and right insula had the highest selectivity for changes in self-location and first-person perspective. Finally, functional connectivity revealed hemispheric differences showing that self-location and first-person perspective modulated the connectivity between right TPJ, right posterior insula, and right supplementary motor area, and between left TPJ and right anterior insula. The present data extend previous evidence on healthy populations and clinical observations in neurological deficits, supporting a bilateral, but right-hemispheric dominant, network for bodily self-consciousness.     

Structural changes in the gray matter of unmedicated patients with obsessive-compulsive disorder: a voxel-based morphometric study

The aim of the current study was to use whole brain voxel-based morphometry（VBM）to assess the gray matter（GM）changes in unmedicated patients with obsessive-compulsive disorder（OCD）compared with normal controls.We compared the GM volumes in28 patients with 22 matched healthy controls using a1.5T MRI.Three-dimensional T1-weighted magnetic resonance images were obtained from all participants.VBM was performed to detect GM volume differences between the two groups.We detected increased regional GM volumes in the bilateral middle temporal gyri,bilateral middle occipital gyri,bilateral globus pallidus,right inferior parietal gyrus,left superior parietal gyrus,right parahippocampus,right supramarginal gyrus,right medial superior frontal gyrus,and left inferior frontal opercular cortex in the OCD patients relative to controls（P〈0.001,uncorrected,cluster size〉100 voxels）.No decreased GM volume was found in the OCD group compared with normal controls.Our findings suggest that structural changes in the GM are not limited to fronto-striato-thalamic circuits in the pathogenesis of OCD.Temporo-parietal cortex may also play an important role.