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 Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness

Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals.     

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.     

Reduction in gray matter of cerebellum in schizophrenia and its influence on static and dynamic connectivity

Pathophysiological and atrophic changes in the cerebellum have been well‐documented in schizophrenia. Reduction of gray matter (GM) in the cerebellum was confirmed across cognitive and motor cerebellar modules in schizophrenia. Such abnormalities in the cerebellum could potentially have widespread effects on both sensorimotor and cognitive symptoms. In this study, we investigated how reduction change in the cerebellum affects the static and the dynamic functional connectivity (FC) between the cerebellum and cortical/subcortical networks in schizophrenia. Reduction of GM in the cerebellum was confirmed across the cognitive and motor cerebellar modules in schizophrenic subjects. Results from this study demonstrates that the extent of reduction of GM within cerebellum correlated with increased static FCs between the cerebellum and the cortical/subcortical networks, including frontoparietal network (FPN), and thalamus in patients with schizophrenia. Decreased GM in the cerebellum was also associated with a declined dynamic FC between the cerebellum and the FPN in schizophrenic subjects. The severity of patients' positive symptom was related to these structural‐functional coupling score of cerebellum. These findings identified potential cerebellar driven functional changes associated with positive symptom deficits. A post hoc analysis exploring the effect of changed FC within cerebellum, confirmed that a significant positive relationship, between dynamic FCs of cerebellum–thalamus and intracerebellum existed in patients, but not in controls. The reduction of GM within the cerebellum might be associated with modulation of cerebellum–thalamus, and contributes to the dysfunctional cerebellar‐cortical communication in schizophrenia. Our results provide a new insight into the role of cerebellum in understanding the pathophysiological of schizophrenia.     

Bridging the gap between functional and anatomical features of cortico‐cerebellar circuits using meta‐analytic connectivity modeling

Theories positing that the cerebellum contributes to cognitive as well as motor control are driven by two sources of information: (1) studies highlighting connections between the cerebellum and both prefrontal and motor territories, (2) functional neuroimaging studies demonstrating cerebellar activations evoked during the performance of both cognitive and motor tasks. However, almost no studies to date have combined these two sources of information and investigated cortico‐cerebellar connectivity during task performance. Through the use of a novel neuroimaging tool (Meta‐Analytic Connectivity Modelling) we demonstrate for the first time that cortico‐cerebellar connectivity patterns seen in anatomical studies and resting fMRI are also present during task performance. Consistent with human and nonhuman primate anatomical studies cerebellar lobules Crus I and II were significantly coactivated with prefrontal and parietal cortices during task performance, whilst lobules HV, HVI, HVIIb, and HVIII were significantly coactivated with the pre‐ and postcentral gyrus. An analysis of the behavioral domains showed that these circuits were driven by distinct tasks. Prefrontal‐parietal‐cerebellar circuits were more active during cognitive and emotion tasks whilst motor‐cerebellar circuits were more active during action execution tasks. These results highlight the separation of prefrontal and motor cortico‐cerebellar loops during task performance, and further demonstrate that activity within these circuits relates to distinct functions. Hum Brain Mapp 35:3152–3169, 2014. © 2013 Wiley Periodicals, Inc.     

Cerebellar networks in individuals at ultra high‐risk of psychosis: Impact on postural sway and symptom severity

Despite known deficits in postural control in patients with schizophrenia, this domain has not been investigated in youth at ultra high‐risk (UHR) for psychosis. This is particularly relevant as postural control implicates dysfunction in the cerebellum‐a region implicated in cognitive dysmetria conceptions of schizophrenia but poorly understood in the prodrome. Here, we extended our understanding of movement abnormalities in UHR individuals to include postural control, and have linked these deficits to both symptom severity and cerebello‐cortical network connectivity. UHR and healthy control participants completed an instrumentally based balance task to quantify postural control along with a resting state brain imaging scan to investigate cerebellar networks. We also quantified positive and negative symptom severity with structured clinical interviews. The UHR group showed overall increased postural sway and decreased cerebello‐cortical resting state connectivity, relative to controls. The decreased cerebello‐cortical connectivity was seen across multiple networks. Postural sway was also correlated with cerebellar connectivity in this population and uniquely positively correlated with the severity of negative symptoms. Finally, symptom severity was also associated with cerebellar connectivity. Together, our results point to a potential deficit in sensory integration as an underlying contributor to the increased postural sway, and provide evidence of cerebellar abnormalities in UHR individuals. These results extend our understanding of the motor abnormalities of UHR individuals beyond striatum‐based dyskinesias to include postural control and sensory integration deficits, and implicate the cerebellum as a distinct neural substrate preceding the onset of psychosis. Taken together, our results extend the cognitive dysmetria framework to UHR populations. Hum Brain Mapp 35:4064–4078, 2014. © 2014 Wiley Periodicals, Inc .     

Specific cerebellar activation during Braille reading in blind subjects

The traditional view that the cerebellum is involved only in the control of movements has been changed recently. It has been suggested that the human cerebellum is involved in cognition and language. Likewise, besides cortical activity in sensorimotor and visual areas, an increased global activation of the cerebellum has been revealed during Braille reading in blind subjects. Our purpose was to investigate whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements. Early blind and normal sighted subjects were studied with functional magnetic resonance imaging (fMRI) during Braille reading, tactile discrimination of nonsense dots, dots forming symbols, and finger tapping. The experiments were done in block design. Echo planar imaging sequences were carried out on a 1.5-T MR scanner. All blind individuals reading Braille showed robust activation of the posterior and lateral aspects of cerebellar hemispheral lobules Crus I bilaterally but more predominately on the right side. Additionally, activation was present in the medial cerebellum within lobules IV, V, and VIIIA, predominantly on the right. Discriminating nonsense dots did not reveal any activation of Crus I, but did reveal activation within the medial part of lobules IV, V, and VIIIA, predominately on the right. Analysis of sighted subjects during reading of printed text revealed activation of the posterolateral cerebellar hemisphere in Crus I bilaterally, predominantly on the right. Tactile analysis of dots representing symbols revealed an activation in lobules IV and VIII and in right Crus II but not in Crus I. In conclusion, parts of cerebellar activation during Braille reading in blind subjects (i.e., within lobules IV, V, and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. Cerebellar activation during Braille reading within bilateral Crus I may be due to language processes or inner speech similar to those found during text reading in normal sighted subjects. Object recognition did not account for Crus I activation.     

Patterned functional network disruption in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor function, with additional evidence of extensive nonmotor involvement. Despite increasing recognition of the disease as a multisystem network disorder characterised by impaired connectivity, the precise neuroelectric characteristics of impaired cortical communication remain to be fully elucidated. Here, we characterise changes in functional connectivity using beamformer source analysis on resting‐state electroencephalography recordings from 74 ALS patients and 47 age‐matched healthy controls. Spatiospectral characteristics of network changes in the ALS patient group were quantified by spectral power, amplitude envelope correlation (co‐modulation) and imaginary coherence (synchrony). We show patterns of decreased spectral power in the occipital and temporal (δ‐ to β‐band), lateral/orbitofrontal (δ‐ to θ‐band) and sensorimotor (β‐band) regions of the brain in patients with ALS. Furthermore, we show increased co‐modulation of neural oscillations in the central and posterior (δ‐, θ‐ and γ_l‐band) and frontal (δ‐ and γ_l‐band) regions, as well as decreased synchrony in the temporal and frontal (δ‐ to β‐band) and sensorimotor (β‐band) regions. Factorisation of these complex connectivity patterns reveals a distinct disruption of both motor and nonmotor networks. The observed changes in connectivity correlated with structural MRI changes, functional motor scores and cognitive scores. Characteristic patterned changes of cortical function in ALS signify widespread disease‐associated network disruption, pointing to extensive dysfunction of both motor and cognitive networks. These statistically robust findings, that correlate with clinical scores, provide a strong rationale for further development as biomarkers of network disruption for future clinical trials.     

Subcortical contributions to effective connectivity in brain networks supporting imitation

Using functional magnetic resonance imaging (fMRI), we investigated effective connectivity in brain networks supporting imitation. Despite extensive reports of regional functional specialization underlying action perception, action execution and imitation, our understanding of the potential contribution of subcortical sites is limited, as is our knowledge of how regions displaying functional specialization interact with each other on a system level. While in the scanner, participants performed a simple imitation paradigm with three conditions: Observe trials, in which participants passively viewed a human actor executing a sequence of four finger presses on a keypad; Imitate trials, in which participants imitated the actor's finger presses on a keyboard; and Execute trials, in which participants also executed finger presses but did so based on visuospatial cues in the absence of the actor's hand. Relative to the Execute condition, Imitate trials evoked significantly more activity in superior and inferior parietal lobules (SPL, IPL), posterior superior temporal sulcus (pSTS), and in a ventral aspect of dorsal premotor cortex (PMd). Psychophysiological interaction (PPI) analysis, a means of assessing effective connectivity, revealed significant interactions with regions of cerebellar lobule VII from seeds both in the right pSTS and right SPL, such that activity in these sites was more highly correlated during imitation. A similar interaction was found between right pSTS and left IPL. These results clarify the role of cortical regions supporting action observation, action execution and imitation, and highlight the role the cerebellum may play in facilitating both motor and nonmotor aspects of imitation.     

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.     

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.     

Key functional circuitry altered in schizophrenia involves parietal regions associated with sense of self

There is still no clear consensus as to which of the many functional and structural changes in the brain in schizophrenia are of most importance, although the main focus to date has been on those in the frontal and cingulate cortices. In the present study, we have used a novel holistic approach to identify brain‐wide functional connectivity changes in medicated schizophrenia patients, and functional connectivity changes were analyzed using resting‐state fMRI data from 69 medicated schizophrenia patients and 62 healthy controls. As far as we are aware, this is the largest population reported in the literature for a resting‐state study. Voxel‐based morphometry was also used to investigate gray and white matter volume changes. Changes were correlated with illness duration/symptom severity and a support vector machine analysis assessed predictive validity. A network involving the inferior parietal lobule, superior parietal gyrus, precuneus, superior marginal, and angular gyri was by far the most affected (68% predictive validity compared with 82% using all connections) and different components correlated with illness duration and positive and negative symptom severity. Smaller changes occurred in emotional memory and sensory and motor processing networks along with weakened interhemispheric connections. Our findings identify the key functional circuitry altered in schizophrenia involving the default network midline cortical system and the cortical mirror neuron system, both playing important roles in sensory and cognitive processing and particularly self‐processing, all of which are affected in this disorder. Interestingly, the functional connectivity changes with the strongest links to schizophrenia involved parietal rather than frontal regions. Hum Brain Mapp 35:123–139, 2014. © 2012 Wiley Periodicals, Inc.     

Musical training induces functional and structural auditory‐motor network plasticity in young adults

Playing music requires a strong coupling of perception and action mediated by multimodal integration of brain regions, which can be described as network connections measured by anatomical and functional correlations between regions. However, the structural and functional connectivities within and between the auditory and sensorimotor networks after long‐term musical training remain largely uninvestigated. Here, we compared the structural connectivity (SC) and resting‐state functional connectivity (rs‐FC) within and between the two networks in 29 novice healthy young adults before and after musical training (piano) with those of another 27 novice participants who were evaluated longitudinally but with no intervention. In addition, a correlation analysis was performed between the changes in FC or SC with practice time in the training group. As expected, participants in the training group showed increased FC within the sensorimotor network and increased FC and SC of the auditory‐motor network after musical training. Interestingly, we further found that the changes in FC within the sensorimotor network and SC of the auditory‐motor network were positively correlated with practice time. Our results indicate that musical training could induce enhanced local interaction and global integration between musical performance‐related regions, which provides insights into the mechanism of brain plasticity in young adults.     

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.     

Topography of Cerebellar Deficits in Humans

The cerebellum is a key-piece for information processing and is involved in numerous motor and nonmotor activities, thanks to the anatomical characteristics of the circuitry, the enormous computational capabilities and the high connectivity to other brain areas. Despite its uniform cytoarchitecture, cerebellar circuitry is segregated into functional zones. This functional parcellation is driven by the connectivity and the anatomo-functional heterogeneity of the numerous extra-cerebellar structures linked to the cerebellum, principally brain cortices, precerebellar nuclei and spinal cord. Major insights into cerebellar functions have been gained with a detailed analysis of the cerebellar outputs, with the evidence that fundamental aspects of cerebrocerebellar operations are the closed-loop circuit and the predictions of future states. Cerebellar diseases result in disturbances of accuracy of movements and lack of coordination. The cerebellar syndrome includes combinations of oculomotor disturbances, dysarthria and other speech deficits, ataxia of limbs, ataxia of stance and gait, as well as often more subtle cognitive/behavioral impairments. Our understanding of the corresponding anatomo-functional maps for the human cerebellum is continuously improving. We summarize the topography of the clinical deficits observed in cerebellar patients and the growing evidence of a regional subdivision into motor, sensory, sensorimotor, cognitive and affective domains. The recently described topographic dichotomy motor versus nonmotor cerebellum based upon anatomical, functional and neuropsychological studies is also discussed.     

l‐Dopa responsiveness is associated with distinctive connectivity patterns in advanced Parkinson's disease

Background : Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. Methods : To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to l ‐dopa, 19 patients with advanced Parkinson's disease underwent resting‐state functional magnetic resonance imaging in the on‐medication state. Scans were obtained on a 3‐Tesla scanner in 3 × 3 × 2.5 mm³ voxels. Seed‐based bivariate regression analyses were carried out with atlas‐defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS‐III following an l ‐dopa challenge. False discovery rate‐corrected P was set at < 0.05 for a 2‐tailed t test. Results : A greater improvement in UPDRS‐III scores following l ‐dopa administration was characterized by higher resting‐state functional connectivity between the prefrontal cortex and the striatum (P = 0.001) and lower resting‐state functional connectivity between the pallidum (P = 0.001), subthalamic nucleus (P = 0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). Conclusions : Our findings show characteristic basal ganglia resting‐state functional connectivity patterns associated with different degrees of l‐ dopa responsiveness in patients with advanced Parkinson's disease. l‐ Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response. © 2017 International Parkinson and Movement Disorder Society     

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.     

Functional connectivity associated with gait velocity during walking and walking‐while‐talking in aging: A resting‐state fMRI study

Gait decline is common among older adults and is a risk factor for adverse outcomes. Poor gait performance in dual‐task conditions, such as walking while performing a secondary cognitive interference task, is associated with increased risk of frailty, disability, and death. Yet, the functional neural substrates that support locomotion are not well established. We examined the functional connectivity associated with gait velocity in single‐ (normal pace walking) and dual‐task (walking while talking) conditions using resting‐state functional Magnetic Resonance Imaging (fMRI). We acquired 6 minutes of resting‐state fMRI data in 30 cognitively healthy older adults. Independent components analyses were performed to separate resting‐state fMRI data into group‐level statistically independent spatial components that correlated with gait velocity in single‐ and dual‐task conditions. Gait velocity in both task conditions was associated with similar functional connectivity in sensorimotor, visual, vestibular, and left fronto‐parietal cortical areas. Compared to gait velocity in the single‐task condition, the networks associated with gait velocity in the dual‐task condition were associated with greater functional connectivity in supplementary motor and prefrontal regions. Our findings show that there are partially overlapping functional networks associated with single‐ and dual‐task walking conditions. These initial findings encourage the future use of resting‐state fMRI as tool in developing a comprehensive understanding of age‐related mobility impairments. Hum Brain Mapp 36:1484–1493, 2015. © 2014 Wiley Periodicals, Inc.     

Linking resting‐state networks and social cognition in schizophrenia and bipolar disorder

Individuals with schizophrenia and bipolar disorder show alterations in functional neural connectivity during rest. However, resting‐state network (RSN) disruptions have not been systematically compared between the two disorders. Further, the impact of RSN disruptions on social cognition, a key determinant of functional outcome, has not been studied. Forty‐eight individuals with schizophrenia, 46 with bipolar disorder, and 48 healthy controls completed resting‐state functional magnetic resonance imaging. An atlas‐based approach was used to examine functional connectivity within nine RSNs across the cortex. RSN connectivity was assessed via nonparametric permutation testing, and associations with performance on emotion perception, mentalizing, and emotion management tasks were examined. Group differences were observed in the medial and lateral visual networks and the sensorimotor network. Individuals with schizophrenia demonstrated reduced connectivity relative to healthy controls in all three networks. Individuals with bipolar disorder demonstrated reduced connectivity relative to controls in the medial visual network and connectivity within this network was significantly positively correlated with emotion management. In healthy controls, connectivity within the medial and lateral visual networks positively correlated with mentalizing. No significant correlations were found for either visual network in schizophrenia. Results highlight the role of altered early visual processing in social cognitive deficits in both schizophrenia and bipolar disorder. However, individuals with bipolar disorder appear to compensate for disrupted visual network connectivity on social cognitive tasks, whereas those with schizophrenia do not. The current study adds clarity on the neurophysiology underlying social cognitive deficits that result in impaired functioning in serious mental illness.     

Sensorimotor,language, and working memory representation within the human cerebellum

The cerebellum is involved in a wide range of behaviours. A key organisational principle from animal studies is that somatotopically corresponding sensory input and motor output reside in the same cerebellar cortical areas. However, compelling evidence for a similar arrangement in humans and whether it extends to cognitive functions is lacking. To address this, we applied cerebellar optimised whole‐brain functional MRI in 20 healthy subjects. To assess spatial overlap within the sensorimotor and cognitive domains, we recorded activity to a sensory stimulus (vibrotactile) and a motor task; the Sternberg verbal working memory (VWM) task; and a verb generation paradigm. Consistent with animal data, sensory and motor activity overlapped with a somatotopic arrangement in ipsilateral areas of the anterior and posterior cerebellum. During the maintenance phase of the Sternberg task, a positive linear relationship between VWM load and activity was observed in right Lobule VI, extending into Crus I bilaterally. Articulatory movement gave rise to bilateral activity in medial Lobule VI. A conjunction of two independent language tasks localised activity during verb generation in right Lobule VI‐Crus I, which overlapped with activity during VWM. These results demonstrate spatial compartmentalisation of sensorimotor and cognitive function in the human cerebellum, with each area involved in more than one aspect of a given behaviour, consistent with an integrative function. Sensorimotor localisation was uniform across individuals, but the representation of cognitive tasks was more variable, highlighting the importance of individual scans for mapping higher order functions within the cerebellum.