Altered resting-state functional connectivity of the cerebellum in schizophrenia

Structural and functional abnormalities of the cerebellum in schizophrenia have been reported. Most previous studies investigating resting-state functional connectivity (rsFC) have relied on a priori restrictions on seed regions or specific networks, which may bias observations. In this study, we aimed to elicit the connectivity alterations of the cerebellum in schizophrenia in a hypothesis-free approach. Ninety-five schizophrenia patients and 93 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). A voxel-wise data-driven method, resting-state functional connectivity density (rsFCD), was used to investigate cerebellar connectivity changes in schizophrenia patients. Regions with altered rsFCD were chosen as seeds to perform seed-based resting-state functional connectivity (rsFC) analyses. We found that schizophrenia patients exhibited decreased rsFCD in the right hemispheric VI; moreover, this cerebellar region showed increased rsFC with the prefrontal cortex and subcortical nuclei and decreased rsFC with the visual cortex and sensorimotor cortex. In addition, some rsFC changes were associated with positive symptoms. These findings suggest that abnormalities of the cerebellar hub and cerebellar-subcortical-cortical loop may be the underlying mechanisms of schizophrenia.     

Cerebellar-parietal dysfunctions in multiple sclerosis patients with cerebellar signs

Consistent findings have shown that the cerebellum is critically implicated in a broad range of cognitive processes including executive functions. Of note, cerebellar symptoms and a number of cognitive deficits have been widely reported in patients with multiple sclerosis (MS). This study investigated for the first time the role of cerebellar symptoms in modulating the neural networks associated with a cognitive task broadly used in MS patients (Paced Visual Serial Addition Test (PVSAT)). Twelve relapsing-remitting (RR) MS patients with prevalent cerebellar signs and symptoms (RR-MSc), 15 RR-MS patients without cerebellar manifestation (RR-MSnc) and 16 matched-healthy controls were examined during functional magnetic resonance imaging (fMRI). We tested whether the RR-MSc patients displayed abnormal activations within "cognitive" cerebellar regions and other areas typically engaged in working memory and tightly connected with the cerebellum. Despite similar behavioral performances during fMRI, RR-MSc patients displayed, relatively to both RR-MSnc patients and controls, significantly greater responses in the left cerebellar Crus I/Lobule VI. RR-MSc patients also displayed reduced functional connectivity between the left cerebellar Crus I and the right superior parietal lobule (FWE<.05). These results demonstrated that the presence of the cerebellar signs drastically impacts on the neurofunctional networks underlying working memory in MS. The altered communication between the cerebellum and a cortical area implicated in short-term buffering and storage of relevant information, offer new insights into the pathophysiological mechanisms of cognition in MS.     

Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing

Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum’s involvement in reading and reading impairment.     

Distinct critical cerebellar subregions for components of verbal working memory

A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between cognitive performance and cerebellar integrity in a specific degeneration of the cerebellar cortex: Spinocerebellar Ataxia type 6 (SCA6). The results demonstrate a critical relationship between verbal working memory and grey matter density in superior (bilateral lobules VI and crus I of lobule VII) and inferior (bilateral lobules VIIIa and VIIIb, and right lobule IX) parts of the cerebellum. We demonstrate that distinct cerebellar regions subserve different components of the prevalent psychological model for verbal working memory based on a phonological loop. The work confirms the involvement of the cerebellum in verbal working memory and defines specific subsystems for this within the cerebellum.     

Cerebellar Neural Circuits Involving Executive Control Network Predict Response to Group Cognitive Behavior Therapy in Social Anxiety Disorder

Some intrinsic connectivity networks including the default mode network (DMN) and executive control network (ECN) may underlie social anxiety disorder (SAD). Although the cerebellum has been implicated in the pathophysiology of SAD and several networks relevant to higher-order cognition, it remains unknown whether cerebellar areas involved in DMN and ECN exhibit altered resting-state functional connectivity (rsFC) with cortical networks in SAD. Forty-six patients with SAD and 64 healthy controls (HC) were included and submitted to the baseline resting-state functional magnetic resonance imaging (fMRI). Seventeen SAD patients who completed post-treatment clinical assessments were included after group cognitive behavior therapy (CBT). RsFC of three cerebellar subregions in both groups was assessed respectively in a voxel-wise way, and these rsFC maps were compared by two-sample t tests between groups. Whole-brain voxel-wise regression was performed to examine whether cerebellar connectivity networks can predict response to CBT. Lower rsFC circuits of cerebellar subregions compared with HC at baseline (p < 0.05, corrected by false discovery rate) were revealed. The left Crus I rsFC with dorsal medial prefrontal cortex was negatively correlated with symptom severity. The clinical assessments in SAD patients were significantly decreased after CBT. Higher pretreatment cerebellar rsFC with angular gyrus and dorsal lateral frontal cortex corresponded with greater symptom improvement following CBT. Cerebellar rsFC circuits involving DMN and ECN are possible neuropathologic mechanisms of SAD. Stronger pretreatment cerebellar rsFC circuits involving ECN suggest potential neural markers to predict CBT response.     

Abnormal functional connectivity in patients with vascular cognitive impairment, no dementia: a resting-state functional magnetic resonance imaging study

The functional connectivity (FC) method was used to investigate the changes in the resting state of patients with vascular cognitive impairment, no dementia (VCIND). Resting-state functional magnetic resonance images (fMRIs) were acquired from 16 patients with subcortical ischemic vascular disease (SIVD) who fulfilled the criteria for VCIND, as well as 18 age- and sex-matched subjects with SIVD with no cognitive impairment (control group). Posterior cingulate cortex connectivity was gathered by investigating synchronic low-frequency fMRI signal fluctuations with a temporal correlation method. Compared with the control group, the patients showed FC decrease in the left middle temporal gyrus, the left anterior cingulate/left middle frontal gyrus, the right caudate, the right middle frontal gyrus, and the left medial frontal gyrus/paracentral lobule. There were also some regions that showed increased connectivity. These regions included the right inferior temporal gyrus, the left middle temporal gyrus, the left precentral gyrus, and the left superior parietal lobule. Our findings revealed the change in resting-state patterns of neuronal activity in patients with VCIND. This change may be caused by subcortical white matter lesions that destroyed direct and indirect fiber tract connectivity across the cerebral white matter and influenced the cortical FC and hypoperfusion resulted from small vascular disease. The results of the increased connectivity may be evoked by the compensatory recruitment and plasticity mechanism. Our findings suggest that the simplicity and noninvasiveness of this method makes it a potential tool to help thoroughly understand the pathogenesis of VCIND.     

Fronto‐cerebellar dysfunction and dysconnectivity underlying cognition in friedreich ataxia: The IMAGE‐FRDA study

Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder defined by pathology within the cerebellum and spinal tracts. Although FRDA is most readily linked to motor and sensory dysfunctions, reported impairments in working memory and executive functions indicate that abnormalities may also extend to associations regions of the cerebral cortex and/or cerebello‐cerebral interactions. To test this hypothesis, 29 individuals with genetically confirmed FRDA and 34 healthy controls performed a verbal n‐back working memory task while undergoing functional magnetic resonance imaging. No significant group differences were evident in task performance. However, individuals with FRDA had deficits in brain activations both in the lateral cerebellar hemispheres, principally encompassing lobule VI, and the prefrontal cortex, including regions of the anterior insular and rostrolateral prefrontal cortices. Functional connectivity between these brain regions was also impaired, supporting a putative link between primary cerebellar dysfunction and subsequent cerebral abnormalities. Disease severity and genetic markers of disease liability were correlated specifically with cerebellar dysfunction, while correlations between behavioural performance and both cerebral activations and cerebello‐cerebral connectivity were observed in controls, but not in the FRDA cohort. Taken together, these findings support a diaschisis model of brain dysfunction, whereby primary disease effects in the cerebellum result in functional changes in downstream fronto‐cerebellar networks. These fronto‐cerebellar disturbances provide a putative biological basis for the nonmotor symptoms observed in FRDA, and reflect the consequence of localized cerebellar pathology to distributed brain function underlying higher‐order cognition. Hum Brain Mapp 37:338–350, 2016. © 2015 Wiley Periodicals, Inc.     

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。     

Functional disconnection of the right anterior insula in obstructive sleep apnea

BackgroundThe right anterior insula (AIns) is an important node of the salience network and serves to switch between two major cognitive-related functional brain networks, ie, the central executive network (CEN) and the default mode network (DMN), both of which show functional deficits in obstructive sleep apnea (OSA) patients. However, the effect of OSA on functional connectivity of the right AIns remains uncertain.ObjectiveTo determine whether the resting-state functional connectivity (rsFC) between the right AIns and the CEN and DMN is disrupted in OSA patients, which may be associated with cognitive deficits in this disorder.MethodsTwenty-four male OSA patients and 21 matched healthy controls underwent functional MRI examinations and clinical and neuropsychologic assessments. The rsFCs between the right AIns and the CEN and DMN were compared between the two groups and were correlated with clinical and neuropsychologic assessments.ResultsCompared with healthy controls, OSA patients showed significantly weakened rsFC between the right AIns and the DMN. Moreover, the functional disconnection between the right AIns and the medial prefrontal cortex was correlated with the severity of the OSA; and the functional disconnection between the right AIns and the posterior cingulate cortex was correlated with depressive scores and working memory performance. However, there were no significant inter-group differences in the rsFC between the right AIns and the CEN.ConclusionsThese findings suggest that OSA selectively impairs the rsFC between the right AIns and the DMN, which may be a candidate substrate for cognitive impairment in OSA patients.     

Temporal dynamics of cerebro-cerebellar network recruitment during a cognitive task

Previous investigations have demonstrated that two regions in the right cerebellum, one located superiorly in hemispheral lobule VI/Crus I and another located inferiorly in hemispheral lobule VIIB/VIIIA, are activated during verbal working memory performance. On the basis of functional neuroimaging patterns of activation, as well as known cortico-pontine and ponto-cerebellar projections, the superior region has been hypothesized to contribute to the articulatory control system of working memory whereas the inferior region has been linked to the phonological store. The present study used event-related fMRI and individual estimates of hemodynamic response for both the cerebellum and neocortex to test this model and characterize the task phase specific cerebro-cerebellar activations for a Sternberg verbal working memory task. Results demonstrated that the right superior cerebellum showed the strongest activation during the initial encoding phase of the task, and, consistent with predictions, a similar pattern was observed in left opercular inferior frontal and premotor regions. In contrast, the right inferior cerebellum exhibited the greatest activation during the maintenance phase of the task, and as predicted, corresponded with activation in the left inferior parietal lobule. The significance of the results with respect to cerebro-cerebellar models of verbal working memory and to theoretical accounts of cerebellar involvement in cognition is discussed.     

Default network connectivity during a working memory task

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task‐related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task‐related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task‐positive networks at rest. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Alterations of voxel‐wise spontaneous activity and corresponding brain functional networks in multiple system atrophy patients with mild cognitive impairment

Emerging evidence has indicated that cognitive impairment is an underrecognized feature of multiple system atrophy (MSA). Mild cognitive impairment (MCI) is related to a high risk of dementia. However, the mechanism underlying MCI in MSA remains controversial. In this study, we conducted the amplitude of low‐frequency fluctuation (ALFF) and seed‐based functional connectivity (FC) analyses to detect the characteristics of local neural activity and corresponding network alterations in MSA patients with MCI (MSA‐MCI). We enrolled 80 probable MSA patients classified as cognitively normal (MSA‐NC, n = 36) and MSA‐MCI (n = 44) and 40 healthy controls. Compared with MSA‐NC, MSA‐MCI exhibited decreased ALFF in the right dorsal lateral prefrontal cortex (RDLPFC) and increased ALFF in the right cerebellar lobule IX and lobule IV–V. In the secondary FC analyses, decreased FC in the left inferior parietal lobe (IPL) was observed when we set the RDLPFC as the seed region. Decreased FC in the bilateral cuneus, left precuneus, and left IPL and increased FC in the right middle temporal gyrus were shown when we set the right cerebellar lobule IX as the seed region. Furthermore, FC of DLPFC‐IPL and cerebello‐cerebral circuit, as well as ALFF alterations, were significantly correlated with Montreal Cognitive Assessment scores in MSA patients. We also employed whole‐brain voxel‐based morphometry analysis, but no gray matter atrophy was detected between the patient subgroups. Our findings indicate that altered spontaneous activity in the DLPFC and the cerebellum and disrupted DLPFC‐IPL, cerebello‐cerebral networks are possible biomarkers of early cognitive decline in MSA patients.     

Cerebellar transcranial magnetic stimulation impairs verbal working memory

Previous functional magnetic resonance imaging and patient studies indicate cerebellar participation in verbal working memory. In particular, event-related functional magnetic resonance imaging showed superior cerebellar activation during the initial encoding phase of the Sternberg task. This study used functional magnetic resonance imaging-guided transcranial magnetic stimulation (TMS) to test whether disruption of the right superior cerebellum (hemispheric lobule VI/Crus I) impairs verbal working memory performance. Single-pulse TMS was administered immediately after letter presentation during the encoding phase on half the trials. Sham TMS and a Motor Control task were included to test for general distraction and nonmemory-related motor effects. Results showed no effects of TMS on accuracy, but reaction times (RTs) on correct trials were significantly increased on TMS relative to non-TMS trials for the Verbal Working Memory and Motor Control tasks. Additional analyses showed that the increased RT was significantly greater for Verbal Working Memory than for the motor task, suggesting that the effect on working memory was not caused by interference with finger responses. Sham TMS did not affect RTs, indicating that the potentially distracting effects of the postencoding click did not contribute to the increase in RT. The observed effects from cerebellar disruption are consistent with proposed cerebrocerebellar involvement in verbal working memory.     

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 cerebellum after trauma: Resting‐state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype

The cerebellum plays a key role not only in motor function but also in affect and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Accordingly, we compared seed‐based resting‐state functional connectivity of the anterior cerebellum (lobule IV–V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD + DS; n = 37), and non‐trauma‐exposed healthy controls (HC; n = 47). Here, we observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in somatosensory processing, multisensory integration, and bodily self‐consciousness (temporo‐parietal junction, postcentral gyrus, and superior parietal lobule) in PTSD + DS as compared to PTSD and HC. Moreover, the PTSD + DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation (ventromedial prefrontal and orbito‐frontal cortex, subgenual anterior cingulum) as compared to PTSD. By contrast, PTSD showed increased functional connectivity of the anterior cerebellum with cortical areas associated with visual processing (fusiform gyrus), interoceptive awareness (posterior insula), memory retrieval, and contextual processing (hippocampus) as compared to HC. Finally, we observed decreased functional connectivity between the posterior cerebellum and prefrontal regions involved in emotion regulation, in PTSD as compared to HC. These findings not only highlight the crucial role of each cerebellar region examined in the psychopathology of PTSD but also reveal unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD versus PTSD.     

Cerebellar–cortical dysconnectivity in resting‐state associated with sensorimotor tasks in schizophrenia

Abnormalities of cerebellar function have been implicated in the pathophysiology of schizophrenia. Since the cerebellum has afferent and efferent projections to diverse brain regions, abnormalities in cerebellar lobules could affect functional connectivity with multiple functional systems in the brain. Prior studies, however, have not examined the relationship of individual cerebellar lobules with motor and nonmotor resting‐state functional networks. We evaluated these relationships using resting‐state fMRI in 30 patients with a schizophrenia‐spectrum disorder and 37 healthy comparison participants. For connectivity analyses, the cerebellum was parcellated into 18 lobular and vermal regions, and functional connectivity of each lobule to 10 major functional networks in the cerebrum was evaluated. The relationship between functional connectivity measures and behavioral performance on sensorimotor tasks (i.e., finger‐tapping and postural sway) was also examined. We found cerebellar–cortical hyperconnectivity in schizophrenia, which was predominantly associated with Crus I, Crus II, lobule IX, and lobule X. Specifically, abnormal cerebellar connectivity was found to the cerebral ventral attention, motor, and auditory networks. This cerebellar–cortical connectivity in the resting‐state was differentially associated with sensorimotor task‐based behavioral measures in schizophrenia and healthy comparison participants—that is, dissociation with motor network and association with nonmotor network in schizophrenia. These findings suggest that functional association between individual cerebellar lobules and the ventral attentional, motor, and auditory networks is particularly affected in schizophrenia. They are also consistent with dysconnectivity models of schizophrenia suggesting cerebellar contributions to a broad range of sensorimotor and cognitive operations.     

Cerebellar fMRI Activation Increases with Increasing Working Memory Demands

The aim of the present study was to explore cerebellar contributions to the central executive in n-back working memory tasks using 7-T functional magnetic imaging (fMRI). We hypothesized that cerebellar activation increased with increasing working memory demands. Activations of the cerebellar cortex and dentate nuclei were compared between 0-back (serving as a motor control task), 1-back, and 2-back working memory tasks for both verbal and abstract modalities. A block design was used. Data of 27 participants (mean age 26.6?±?3.8 years, female/male 12:15) were included in group statistical analysis. We observed that cerebellar cortical activations increased with higher central executive demands in n-back tasks independent of task modality. As confirmed by subtraction analyses, additional bilateral activations following higher executive demands were found primarily in four distinct cerebellar areas: (i) the border region of lobule VI and crus I, (ii) inferior parts of the lateral cerebellum (lobules crus II, VIIb, VIII, IX), (iii) posterior parts of the paravermal cerebellar cortex (lobules VI, crus I, crus II), and (iv) the inferior vermis (lobules VI, VIIb, VIII, IX). Dentate activations were observed for both verbal and abstract modalities. Task-related increases were less robust and detected for the verbal n-back tasks only. These results provide further evidence that the cerebellum participates in an amodal bilateral neuronal network representing the central executive during working memory n-back tasks.     

Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing

Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations.     

Cerebellar Clustering and Functional Connectivity During Pain Processing

The cerebellum has been traditionally considered a sensory-motor structure, but more recently has been related to other cognitive and affective functions. Previous research and meta-analytic studies suggested that it could be involved in pain processing. Our aim was to distinguish the functional networks subserved by the cerebellum during pain processing. We used functional magnetic resonance imaging (fMRI) on 12 subjects undergoing mechanical pain stimulation and resting state acquisition. For the analysis of data, we used fuzzy c-mean to cluster cerebellar activity of each participant during nociception. The mean time courses of the clusters were used as regressors in a general linear model (GLM) analysis to explore brain functional connectivity (FC) of the cerebellar clusters. We compared our results with the resting state FC of the same cluster and explored with meta-analysis the behavior profile of the FC networks. We identified three significant clusters: cluster V, involving the culmen and quadrangular lobules (vermis IV-V, hemispheres IV-V-VI); cluster VI, involving the posterior quadrangular lobule and superior semilunar lobule (hemisphere VI, crus 1, crus 2), and cluster VII, involving the inferior semilunar lobule (VIIb, crus1, crus 2). Cluster V was more connected during pain with sensory-motor areas, cluster VI with cognitive areas, and cluster VII with emotional areas. Our results indicate that during the application of mechanical punctate stimuli, the cerebellum is not only involved in sensory functions but also with areas typically associated with cognitive and affective functions. Cerebellum seems to be involved in various aspects of nociception, reflecting the multidimensionality of pain perception.     

Abnormal brain activity patterns during spatial working memory task in patients with end-stage renal disease on maintenance hemodialysis: a fMRI study

Hemodialysis (HD) is associated with cognitive impairment in patients with end-stage renal disease (ESRD). However, the neural mechanism of spatial working memory (SWM) impairment in HD-ESRD patients remains unclear. We investigated the abnormal alterations in SWM-associated brain activity patterns in HD-ESRD patients using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) technique during n-back tasks. Twenty-two HD-ESRD patients and 22 well-matched controls underwent an fMRI scan while undergoing a three-load n-back tasks with different difficulty levels. Cognitive and mental states were assessed using a battery of neuropsychologic tests. The HD-ESRD patients exhibited worse memory abilities than controls. Compared with the control group, the HD-ESRD patient group showed lower accuracy and longer response time under the n-back tasks, especially in the 2-back task. The patterns of brain activation changed under different working memory loads in the HD-ESRD patients, showing decreased activity in the right medial frontal gyrus and inferior frontal gyrus under 0-back and 1-back task, while more decreased activation in the bilateral frontal cortex, parietal lobule, anterior/posterior cingulate cortex and insula cortex under 2-back task. With the increase of task difficulty, the activation degree of the frontal and parietal cortex decreased. More importantly, we found that lower activation in frontal cortex and parietal lobule was associated with worse cognitive function in the HD-ESRD patients. These results demonstrate that the abnormal brain activity patterns of frontal cortex and parietal lobule may reflect the neural mediation of SWM impairment.