Altered resting-state functional connectivity of the dentate nucleus in Parkinson's disease

We used functional magnetic resonance imaging (fMRI) to measure functional connectivity of the dentate nucleus (DN) between patients with Parkinson's disease (PD) and normal controls who were studied in a resting state. Images were acquired in 18 PD patients and in age- and sex-matched normal controls. Connectivity of the bilateral DN was calculated and compared between patients and controls, connectivity of the bilateral DN within the cerebellum was compared between rigidity and bradykinesia-dominant patients (PD_AR) and tremor-dominant patients (PD_T), and correlation analysis was performed between the connectivity strength and behavioral measures within the cerebellum. Some regions in the cerebellum showed enhanced connectivity with the bilateral DN in PD patients, and decreased connectivity of the DN with the bilateral cerebellar posterior lobe was observed in PD_T as compared to PD_AR. A set of regions consistent with the default mode network showed disrupted connectivity with the DN. Decreased connectivity between the inferior parietal lobule and the DN was also observed in PD patients. Additional analyses did not show any significant correlations between functional connectivity within the cerebellum and Unified Parkinson's Disease Rating Scale-III scores. Our findings suggest that connectivity of the DN in the resting state is disrupted in PD, and there may be a compensatory cerebellar connectivity mechanism in the resting state in PD. Further study of the cerebellum may clarify the pathophysiology of PD.     

Attention and Working Memory in Adolescents with Autism Spectrum Disorder: A Functional MRI Study

The present study examined attention and memory load-dependent differences in the brain activation and deactivation patterns between adolescents with autism spectrum disorders (ASDs) and typically developing (TD) controls using functional magnetic resonance imaging. Attentional (0-back) and working memory (WM; 2-back) processing and load differences (0 vs. 2-back) were analysed. WM-related areas activated and default mode network deactivated normally in ASDs as a function of task load. ASDs performed the attentional 0-back task similarly to TD controls but showed increased deactivation in cerebellum and right temporal cortical areas and weaker activation in other cerebellar areas. Increasing task load resulted in multiple responses in ASDs compared to TD and in inadequate modulation of brain activity in right insula, primary somatosensory, motor and auditory cortices. The changes during attentional task may reflect compensatory mechanisms enabling normal behavioral performance. The inadequate memory load-dependent modulation of activity suggests diminished compensatory potential in ASD.     

Cerebellar contributions to biological motion perception in autism and typical development

Growing evidence suggests that posterior cerebellar lobe contributes to social perception in healthy adults. However, they know little about how this process varies across age and with development. Using cross‐sectional fMRI data, they examined cerebellar response to biological (BIO) versus scrambled (SCRAM) motion within typically developing (TD) and autism spectrum disorder (ASD) samples (age 4–30 years old), characterizing cerebellar response and BIO > SCRAM‐selective effective connectivity, as well as associations with age and social ability. TD individuals recruited regions throughout cerebellar posterior lobe during BIO > SCRAM, especially bilateral lobule VI, and demonstrated connectivity with right posterior superior temporal sulcus (RpSTS) in left VI, Crus I/II, and VIIIb. ASD individuals showed BIO > SCRAM activity in left VI and left Crus I/II, and bilateral connectivity with RpSTS in Crus I/II and VIIIb/IX. No between‐group differences emerged in well‐matched subsamples. Among TD individuals, older age predicted greater BIO > SCRAM response in left VIIb and left VIIIa/b, but reduced connectivity between RpSTS and widespread regions of the right cerebellum. In ASD, older age predicted greater response in left Crus I and bilateral Crus II, but decreased effective connectivity with RpSTS in bilateral Crus I/II. In ASD, increased BIO > SCRAM signal in left VI/Crus I and right Crus II, VIIb, and dentate predicted lower social symptomaticity; increased effective connectivity with RpSTS in right Crus I/II and bilateral VI and I–V predicted greater symptomaticity. These data suggest that posterior cerebellum contributes to the neurodevelopment of social perception in both basic and clinical populations. Hum Brain Mapp 38:1914–1932, 2017. © 2017 Wiley Periodicals, Inc.     

Influences of cerebral cortex and cerebellum on the red nucleus of the rat

The aim of the present work was to investigate the unitary responses of neurons belonging to the magnocellular and parvocellular division of the red nucleus (RN) to stimulation of efferents from motor cortex and cerebellum. In anesthetized rats spontaneous discharges of rubro-olivary (RO) and rubrospinal (RS) neurons were tested for stimulation of motor cortex (CX), pyramidal tract (PT), interpositus (IN) and dentate (DN) cerebellar nuclei. It has been observed that the majority of RO and RS neurons were influenced by stimulation of both IN and DN as well as by activation of CX and PT. These results indicate that (1) a segregation of cerebral and cerebellar afferents to RN of rat does not exist and (2) convergent responses from the same cerebral and cerebellar structures have been observed in a high number of both RS and RO neurons.     

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.     

Functional Brain Networks and White Matter Underlying Theory-of-Mind in Autism

Human beings constantly engage in attributing causal explanations to one’s own and to others’ actions, and theory-of-mind (ToM) is critical in making such inferences. Although children learn causal attribution early in development, children with autism spectrum disorders (ASDs) are known to have impairments in the development of intentional causality. This functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study investigated the neural correlates of physical and intentional causal attribution in people with ASDs. In the fMRI scanner, 15 adolescents and adults with ASDs and 15 age- and IQ-matched typically developing peers made causal judgments about comic strips presented randomly in an event-related design. All participants showed robust activation in bilateral posterior superior temporal sulcus at the temporo-parietal junction (TPJ) in response to intentional causality. Participants with ASDs showed lower activation in TPJ, right inferior frontal gyrus and left premotor cortex. Significantly weaker functional connectivity was also found in the ASD group between TPJ and motor areas during intentional causality. DTI data revealed significantly reduced fractional anisotropy in ASD participants in white matter underlying the temporal lobe. In addition to underscoring the role of TPJ in ToM, this study found an interaction between motor simulation and mentalizing systems in intentional causal attribution and its possible discord in autism.     

Cerebellar rTMS stimulation may induce prolonged clinical benefits in essential tremor,and subjacent changes in functional connectivity: An open label trial

BackgroundCerebello-thalamo-cortical (CTC) pathways dysfunction is involved in pathological oscillations causing tremor in essential tremor (ET). Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the cerebellum can effectively modulate the cerebellar output.ObjectiveAs one session of rTMS can induce a brief improvement, we hypothesized that repeated sessions might have a cumulative and potentially long-term therapeutic effect on ET. We assessed, in an open label trial, the efficacy of one-week rTMS treatment on tremor and on the motor-CTC dysfunction in ET patients.MethodsResting-state fMRI functional connectivity was used as an indicator of CTC network integrity in 11 ET patients and 11 healthy subjects. Resting-state fMRI connectivity was quantified at baseline in patients and control subjects between the cerebellum and the motor network, and between the cerebellum and the default brain network (DBN) taken as control. The fMRI study was repeated in patients after 5 days of bilateral 1 Hz rTMS applied to the posterior cerebellar cortex. Tremor was assessed clinically (Fahn–Tolosa–Marin scale) and quantified using electromyographic and accelerometric recordings at baseline (day 1, before the cerebellar stimulation) and after the end of the cerebellar stimulation period at day 5, day 12 and day 29.ResultsRepeated rTMS over the cerebellum significantly improved total and specific (tremor, drawing, functional disability) scores, and reduced tremor amplitude (P < 0.006). It also re-established the defective information processing in the CTC network (P(Δ|y) > 0.909), but not in the DBN. The effects persisted for 3 weeks after the last session.ConclusionCerebellar stimulation could be an effective treatment option for patients with severe essential tremor.     

Breakdown of the affective‐cognitive network in functional dystonia

Previous studies suggested that brain regions subtending affective‐cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective‐cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS‐fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD‐age‐matched [yHC]; 29 old MobFD‐age‐matched [oHC]). FC of brain regions of interest, known to be involved in affective‐cognitive processes, and independent component analysis of RS‐fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective‐cognitive seeds of interest and the fronto‐subcortical and limbic circuits; enhanced FC between the right affective‐cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective‐cognitive seeds of interest and the sensorimotor and high‐order function (“cognitive”) areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective‐cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.     

Metabolic Changes of Cerebrum by Repetitive Transcranial Magnetic Stimulation over Lateral Cerebellum: A Study with FDG PET

To better understand the functional role of cerebellum within the large-scale cerebellocerebral neural network, we investigated the changes of neuronal activity elicited by cerebellar repetitive transcranial magnetic stimulation (rTMS) using (18)F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twelve right-handed healthy volunteers were studied with brain FDG PET under two conditions: active rTMS of 1?Hz frequency over the left lateral cerebellum and sham stimulation. Compared to the sham condition, active rTMS induced decreased glucose metabolism in the stimulated left lateral cerebellum, the areas known to be involved in voluntary motor movement (supplementary motor area and posterior parietal cortex) in the right cerebral hemisphere, and the areas known to be involved in cognition and emotion (orbitofrontal, medial frontal, and anterior cingulate gyri) in the left cerebral hemisphere. Increased metabolism was found in cognition- and language-related brain regions such as the left inferior frontal gyrus including Broca's area, bilateral superior temporal gyri including Wernicke's area, and bilateral middle temporal gyri. Left cerebellar rTMS also led to increased metabolism in the left cerebellar dentate nucleus and pons. These results demonstrate that rTMS over the left lateral cerebellum modulates not only the target region excitability but also excitability of remote, but interconnected, motor-, language-, cognition-, and emotion-related cerebral regions. They provide further evidence that the cerebellum is involved not only in motor-related functions but also in higher cognitive abilities and emotion through the large-scale cerebellocereberal neural network.     

Decreased centrality of cortical volume covariance networks in autism spectrum disorders

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by atypical structural and functional brain connectivity. Complex network analysis has been mainly used to describe altered network-level organization for functional systems and white matter tracts in ASD. However, atypical functional and structural connectivity are likely to be also linked to abnormal development of the correlated structure of cortical gray matter. Such covariations of gray matter are particularly well suited to the investigation of the complex cortical pathology of ASD, which is not confined to isolated brain regions but instead acts at the systems level. In this study, we examined network centrality properties of gray matter networks in adults with ASD (n = 84) and neurotypical controls (n = 84) using graph theoretical analysis. We derived a structural covariance network for each group using interregional correlation matrices of cortical volumes extracted from a surface-based parcellation scheme containing 68 cortical regions. Differences between groups in closeness network centrality measures were evaluated using permutation testing. We identified several brain regions in the medial frontal, parietal and temporo-occipital cortices with reductions in closeness centrality in ASD compared to controls. We also found an association between an increased number of autistic traits and reduced centrality of visual nodes in neurotypicals. Our study shows that ASD are accompanied by atypical organization of structural covariance networks by means of a decreased centrality of regions relevant for social and sensorimotor processing. These findings provide further evidence for the altered network-level connectivity model of ASD.     

Handedness-related functional connectivity using low-frequency blood oxygenation level-dependent fluctuations

Functional neuroimaging studies of handedness have traditionally focused on exploring regionally activated discrepancies, yet little is known regarding the effect of handedness on functional connections of brain regions. Here, we reported the relationship between cerebellar functional connectivity patterns and handedness by low-frequency blood oxygenation level-dependent fluctuations. Compared with the right-handers, the left-handers show higher cerebellar-prefrontal, cerebellar-parietal, and cerebellar-temporal functional connectivity, and lower cerebellar-limbic connectivity. Previous non-human primate studies have shown that these regions with known contributions to higher cognitive functions have afferent or efferent connections with the cerebellum. Our findings suggest that these observed low-frequency fluctuation correlations may reflect actually anatomic connections between the cerebellum and cerebral cortex, and the cerebellar involvement in higher function may be associated with handedness.     

Dysmaturation of the default mode network in autism

Two hypotheses of autism spectrum disorder (ASD) propose that this condition is characterized by deficits in Theory of Mind and by hypoconnectivity between remote cortical regions with hyperconnectivity locally. The default mode network (DMN) is a set of remote, functionally connected cortical nodes less active during executive tasks than at rest and is implicated in Theory of Mind, episodic memory, and other self‐reflective processes. We show that children with ASD have reduced connectivity between DMN nodes and increased local connectivity within DMN nodes and the visual and motor resting‐state networks. We show that, like the trajectory of synaptogenesis, internodal DMN functional connectivity increased as a quadratic function of age in typically developing children, peaking between, 11 and 13 years. In children with ASD, these long‐distance connections fail to develop during adolescence. These findings support the “developmental disconnection model” of ASD, provide a possible mechanistic explanation for the Theory‐of‐Mind hypothesis of ASD, and show that the window for effectively treating ASD could be wider than previously thought. Hum Brain Mapp 35:1284–1296, 2014. © 2013 Wiley Periodicals, Inc.     

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 default network and processing of personally relevant information: Converging evidence from task-related modulations and functional connectivity

Despite a growing interest in the default network (DN), its composition and function are not fully known. Here we examined whether the DN, as a whole, is specifically active during a task involving judgments about the self, or whether this engagement extends to judgments about a close other. We also aimed to provide converging evidence of DN involvement from across-task functional connectivity, and resting-state functional connectivity analyses, to provide a more comprehensive delineation of this network. Using functional MRI we measured brain activity in young adults during tasks and rest, and utilized a multivariate method to assess task-related changes as well as functional connectivity. An overlapping set of regions showed increased activity for judgments about the self, and about a close other, and strong functional connectivity with the posterior cingulate, a critical node of the DN. These areas included ventromedial prefrontal cortex, posterior parietal cortex, and medial temporal regions, all thought to be part of the DN. Several additional regions, such as the left inferior frontal gyrus and bilateral caudate, also showed the same pattern of activity and connectivity. These results provide evidence that the default network, as an integrated whole, supports internally oriented cognition involving information that is personally relevant, but not limited specifically to the self. They also suggest that the DN may be somewhat more extensive than currently thought.     

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.     

Resting-state fMRI functional connectivity: a new perspective to evaluate pain modulation in migraine?

Resting-state (RS) functional magnetic resonance imaging (fMRI) is a relatively novel tool which explores connectivity between functionally linked, but anatomically separated, brain regions. The use of this technique has allowed the identification, at rest, of the main brain functional networks without requiring subjects to perform specific active tasks. Methodologically, several approaches can be applied for the analysis of RS fMRI, including seed-based, independent component analysis-based and/or cluster-based methods. The most consistently described RS network is the so-called “default mode network”. Using RS fMRI, several studies have identified functional connectivity abnormalities in migraine patients, mainly located at the level of the pain-processing network. RS functional connectivity is generally increased in pain-processing network, whereas is decreased in pain modulatory circuits. Significant abnormalities of RS functional connectivity occur also in affective networks, the default mode network and the executive control network. These results provide a strong characterization of migraine as a brain dysfunction affecting intrinsic connectivity of brain networks, possibly reflecting the impact of long lasting pain on brain function.     

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.     

Interhemispheric Connectivity Characterizes Cortical Reorganization in Motor-Related Networks After Cerebellar Lesions

Although cerebellar-cortical interactions have been studied extensively in animal models and humans using modern neuroimaging techniques, the effects of cerebellar stroke and focal lesions on cerebral cortical processing remain unknown. In the present study, we analyzed the large-scale functional connectivity at the cortical level by combining high-density electroencephalography (EEG) and source imaging techniques to evaluate and quantify the compensatory reorganization of brain networks after cerebellar damage. The experimental protocol comprised a repetitive finger extension task by 10 patients with unilateral focal cerebellar lesions and 10 matched healthy controls. A graph theoretical approach was used to investigate the functional reorganization of cortical networks. Our patients, compared with controls, exhibited significant differences at global and local topological level of their brain networks. An abnormal rise in small-world network efficiency was observed in the gamma band (30–40 Hz) during execution of the task, paralleled by increased long-range connectivity between cortical hemispheres. Our findings show that a pervasive reorganization of the brain network is associated with cerebellar focal damage and support the idea that the cerebellum boosts or refines cortical functions. Clinically, these results suggest that cortical changes after cerebellar damage are achieved through an increase in the interactions between remote cortical areas and that rehabilitation should aim to reshape functional activation patterns. Future studies should determine whether these hypotheses are limited to motor tasks or if they also apply to cerebro-cerebellar dysfunction in general.     

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 Function in Dentate Nuclei Precedes the Onset of Psychosis: A Resting-State fMRI Study in High-Risk Individuals

ObjectiveThe cerebellum serves a wide range of functions and is suggested to be composed of discrete regions dedicated to unique functions. We recently developed a new parcellation of the dentate nuclei (DN), the major output nuclei of the cerebellum, which optimally divides the structure into 3 functional territories that contribute uniquely to default-mode, motor-salience, and visual processing networks as indexed by resting-state functional connectivity (RsFc). Here we test for the first time whether RsFc differences in the DN, precede the onset of psychosis in individuals at risk of developing schizophrenia.MethodsWe used the magnetic resonance imaging (MRI) dataset from the Shanghai At Risk for Psychosis study that included subjects at high risk to develop schizophrenia (N = 144), with longitudinal follow-up to determine which subjects developed a psychotic episode within 1 year of their functional magnetic resonance imaging (fMRI) scan (converters N = 23). Analysis used the 3 functional parcels (default-mode, salience-motor, and visual territory) from the DN as seed regions of interest for whole-brain RsFc analysis.ResultsRsFc analysis revealed abnormalities at baseline in high-risk individuals who developed psychosis, compared to high-risk individuals who did not develop psychosis. The nature of the observed abnormalities was found to be anatomically specific such that abnormal RsFc was localized predominantly in cerebral cortical networks that matched the 3 functional territories of the DN that were evaluated.ConclusionsWe show for the first time that abnormal RsFc of the DN may precede the onset of psychosis. This new evidence highlights the role of the cerebellum as a potential target for psychosis prediction and prevention.