Aberrant Cerebellar–Cerebral Functional Connectivity in Children and Adolescents With Autism Spectrum Disorder

The cerebellum, which forms widespread functional networks with many areas in the cerebral cortices and subcortical structures, is one of the brain regions most consistently reported to exhibit neuropathological features in patients with autism spectrum disorder (ASD). However, cerebellar functional connectivity (FC) studies in patients with ASD have been very sparse. Using resting state functional connectivity (rsFC) analysis, we investigated the FC of the hemispheric/vermal subregions and the dentate nucleus of the cerebellum with the cerebral regions in 36 children and adolescents [16 participants with ASD, 20 typically developing (TD) participants, age: 6–15 years]. Furthermore, an independent larger sample population (42 participants with ASD, 88 TD participants, age: 6–15 years), extracted from the Autism Brain Imaging Data Exchange (ABIDE) II, was included for replication. The ASD group showed significantly increased or decreased FC between “hubs” in the cerebellum and cerebral cortices, when compared with the TD group. Findings of aberrant FCs converged on the posterior hemisphere, right dentate nucleus, and posterior inferior vermis of the cerebellum. Furthermore, these aberrant FCs were found to be related to motor, executive, and socio-communicative functions in children and adolescents with ASD when we examined correlations between FC and behavioral measurements. Results from the original dataset were partially replicated in the independent larger sample population. Our findings suggest that aberrant cerebellar–cerebral FC is associated with motor, socio-communicative, and executive functions in children and adolescents with ASD. These observations improve the current knowledge regarding the neural substrates that underlie the symptoms of ASD

The role of the cerebellum in unconsciuos and conscious processing of emotions: a review

Studies from the past three decades have demonstrated that there is cerebellar involvement in the emotional domain. Emotional processing in humans requires both unconscious and conscious mechanisms. A significant amount of evidence indicates that the cerebellum is one of the cerebral structures that subserve emotional processing, although conflicting data have been reported on its function in unconscious and conscious mechanisms. This review discusses the available clinical, neuroimaging and neurophysiological data on this issue. We also propose a model in which the cerebellum acts as a mediator between the internal state and external environment for the unconscious and conscious levels of emotional processing

Dimensions of Depression and Cerebellar Subregion Volumes in Older Adults

The present study examined the relationship between subthreshold depressive symptoms and gray matter volume in subregions of the posterior cerebellum in middle-aged to older adults. Structural magnetic resonance imaging data from 38 adults aged 51 to 80 years were analyzed along with participants’ responses to the Center for Epidemiologic Studies Depression Scale. Subscale scores for depressed mood, somatic symptoms, and lack of positive affect were calculated, and multiple regression analyses were used to examine the relationship between symptom dimensions and cerebellar volumes. Greater somatic symptoms of depression were significantly related to larger vermis VI volumes, as were total depressive scores. Exploratory analyses revealed that greater severity on the lack of positive affect subscale was related to larger vermis VIII volumes. These results support that depressive symptom profiles have unique relationships within the cerebellum that may be important as the field moves towards targeted treatment approaches for depression

Resting-state functional connectivity changes within the default mode network and the salience network after antipsychotic treatment in early-phase schizophrenia

OBJECTIVE: Abnormal resting-state functional connectivity (FC), particularly in the default mode network (DMN) and the salience network (SN), has been reported in schizophrenia, but little is known about the effects of antipsychotics on these networks. The purpose of this study was to examine the effects of atypical antipsychotics on DMN and SN and the relationship between these effects and symptom improvement in patients with schizophrenia. METHODS: This was a prospective study of 33 patients diagnosed with schizophrenia and treated with antipsychotics at Shanghai Mental Health Center. Thirty-three healthy controls matched for age and gender were recruited. All subjects underwent functional magnetic resonance imaging (fMRI). Healthy controls were scanned only once; patients were scanned before and after 6-8 weeks of treatment. RESULTS: In the DMN, the patients exhibited increased FC after treatment in the right superior temporal gyrus, right medial frontal gyrus, and left superior frontal gyrus and decreased FC in the right posterior cingulate/precuneus (P\u3c0.005). In the SN, the patients exhibited decreased FC in the right cerebellum anterior lobe and left insula (P\u3c0.005). The FC in the right posterior cingulate/precuneus in the DMN negatively correlated with the difference between the Clinical Global Impression (CGI) score pre/post-treatment (r=-0.564, P=0.023) and negative trends with the difference in the Positive and Negative Syndrome Scale (PANSS) total score pre/post-treatment (r=-0.475, P=0.063) and the difference in PANSS-positive symptom scores (r=-0.481, P=0.060). CONCLUSION: These findings suggest that atypical antipsychotics could regulate the FC of certain key brain regions within the DMN in early-phase schizophrenia, which might be related to symptom improvement. However, the effects of atypical antipsychotics on SN are less clear

Cerebello-Cortical Coherence of Local Field Potentials following Patterned Stimulation of the Cerebellar Vermis

The cerebellum is involved in sensorimotor, cognitive, and emotional functions through cerebello- cerebral connectivity. Non-invasive cerebellar neurostimulation has been used to treat neurological disorders and has positive effects on cognition and mood, which have been related to modulation in frontal oscillations. To explore the mechanisms, we studied the effects of cerebellar stimulation at various frequencies on oscillations and coherence across a cerebello-cortical network, in the anesthetized rat. Local field potentials were recorded continuously with monopolar and bipolar electrodes in the lateral cerebellum (crus I/II), and in the prefrontal cortex (FrA), in six adult male Sprague-Dawley rats anesthetized with urethane. Stimulation patterns were delivered to the cerebellar vermis (lobule VII) in a randomized order: single pulses (0.2 Hz for 60 s), and repeated pulses at 1 Hz (30 s), 5 Hz (10 s), 25 Hz (2 s), and 50 Hz (1 s). Low frequency stimulation (1 Hz and 5 Hz) enhanced coherence in the cerebello-cortical network in theta and alpha, while high frequency stimulation (50 Hz) had an enhancing effect on beta and low gamma coherence. Stimulation effects were influenced by the initial oscillatory state, perhaps due to cyclic stages under urethane anesthesia. Low frequency stimulation was more efficient when delivered in a state dominated by slow waves, while high frequency stimulation showed the opposite relationship. We have found here that cerebellar stimulation can drive synchronization of cerebello-cortical and cortico-cortical networks. The present results could provide basic mechanisms underlying the therapeutic effects of cerebellar stimulation by promoting large-scale synchronization of neural networks

Disrupted Cerebellar Connectivity With the Central Executive Network and the Default-Mode Network in Unmedicated Bipolar II Disorder

Objective: Bipolar disorder (BD) is a common psychiatric disease. Although structural and functional abnormalities of the cerebellum in BD patients have been reported by recent neuroimaging studies, the cerebellar-cerebral functional connectivity (FC) has not yet been examined. The present study aims to investigate the FC between the cerebellum and cerebrum, particularly the central executive network (CEN) and the default-mode network (DMN) in bipolar II disorder (BD II).Methods: Ninety-four patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent the resting-state functional magnetic resonance imaging. Seed-based connectivity analyses were performed using cerebellar seeds previously identified as being involved in the CEN (bilateral Crus Ia) and DMN (bilateral Crus Ib).Results: Compared with HCs, BD II depression patients appeared decreased FC in the right Crus Ia-left dorsal lateral prefrontal cortex (dlPFC) and -left anterior cingulate cortex (ACC), the right Crus Ib-left medial prefrontal cortex (mPFC), -left middle temporal gyrus (MTG), and -left inferior temporal gyrus (ITG). No altered FC between the left Crus Ia or Crus Ib and the cerebral regions was found.Conclusions: Patients with BD II depression showed disrupted FC between the cerebellum and the CEN (mainly in the left dlPFC and ACC) and DMN (mainly in the left mPFC and temporal lobe), suggesting the significant role of the cerebellum-CEN and -DMN connectivity in the pathogenesis of BD

The cerebellum, internal models and prediction in 'non-motor' aspects of language: A critical review

The emergence of studies on cerebellar contributions in ‘non-motor’ aspects of predictive language processing has long been awaited by researchers investigating the neural foundations of language and cognition. Despite (i) progress in research implicating the cerebellum in language processing, (ii) the widely-accepted nature of the uniform, multi-modal computation that the cerebellum implements in the form of internal models, as well as (iii) the long tradition of psycholinguistic studies addressing prediction mechanisms, research directly addressing cerebellar contributions to ‘non-motor’ predictive language processing has only surfaced in the last five years. This paper provides the first review of this novel field, along with a critical assessment of the studies conducted so far. While encouraging, the evidence for cerebellar involvement in ‘non-motor’ aspects of predictive language processing remains inconclusive under further scrutiny. Future directions are finally discussed with respect to outstanding questions in this novel field of research

Cerebellar gray matter and lobular volumes correlate with core autism symptoms

AbstractNeuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD), but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM) and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM) and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD) children (mean age 10.4 ± 1.6 years; range 8–13 years). To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on right cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile

The cerebellum, internal models and prediction in 'non-motor' aspects of language: A critical review

The emergence of studies on cerebellar contributions in 'non-motor' aspects of predictive language processing has long been awaited by researchers investigating the neural foundations of language and cognition. Despite (i) progress in research implicating the cerebellum in language processing, (ii) the widely-accepted nature of the uniform, multi-modal computation that the cerebellum implements in the form of internal models, as well as (iii) the long tradition of psycholinguistic studies addressing prediction mechanisms, research directly addressing cerebellar contributions to 'non-motor' predictive language processing has only surfaced in the last five years. This paper provides the first review of this novel field, along with a critical assessment of the studies conducted so far. While encouraging, the evidence for cerebellar involvement in 'non-motor' aspects of predictive language processing remains inconclusive under further scrutiny. Future directions are finally discussed with respect to outstanding questions in this novel field of research