Reduced cerebellar inhibition in schizophrenia: A preliminary study
ABSTRACT Postmortem and structural imaging studies suggest that patients with schizophrenia have disrupted cerebellar activity. It has been speculated that these abnormalities mediate disorganized thought processes and psychosis. The authors' goal was to use transcranial magnetic stimulation to measure cerebellar inhibition, a proxy of cerebellar activity, as the principal output of the cerebellum is inhibitory.
Cerebellar inhibition was accomplished by delivering a magnetic cerebellar conditioning stimulus 5-15 msec before a magnetic test stimulus to the motor cortex. The cerebellar conditioning stimulus inhibits the size of the motor evoked potential produced by the test stimulus by approximately 50%. Ten patients with schizophrenia and 10 healthy comparison subjects completed the cerebellar inhibition protocol.
Patients with schizophrenia demonstrated significant deficits in cerebellar inhibition compared with healthy subjects.
The authors conclude that deficits in cerebellar inhibitory activity in schizophrenia may be the result of an abnormality in the cerebellum or disrupted cerebellar-thalamic-cortical connectivity.
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ABSTRACT: Schizophrenia is a devastating illness characterized by disturbances in multiple domains. The cerebellum is involved in both motor and non-motor functions, and the "cognitive dysmetria" and "dysmetria of thought" models propose that abnormalities of the cerebellum may contribute to schizophrenia signs and symptoms. The cerebellum and cerebral cortex are reciprocally connected via a modular, closed-loop network architecture, but few schizophrenia neuroimaging studies have taken into account the topographical and functional heterogeneity of the cerebellum. In this study, using a previously defined 17-network cerebral cortical parcellation system as the basis for our functional connectivity seeds, we systematically investigated connectivity abnormalities within the cerebellum of 44 schizophrenia patients and 28 healthy control participants. We found selective alterations in cerebro-cerebellar functional connectivity. Specifically, schizophrenia patients showed decreased cerebro-cerebellar functional connectivity in higher level association networks (ventral attention, salience, control, and default mode networks) relative to healthy control participants. Schizophrenia patients also showed increased cerebro-cerebellar connectivity in somatomotor and default mode networks, with the latter showing no overlap with the regions found to be hypoconnected within the same default mode network. Finally, we found evidence to suggest that somatomotor and default mode networks may be inappropriately linked in schizophrenia. The relationship of these dysconnectivities to schizophrenia symptoms, such as neurological soft signs and altered sense of agency, is discussed. We conclude that the cerebellum ought to be considered for analysis in all future studies of network abnormalities in SZ, and further suggest the cerebellum as a potential target for further elucidation, and possibly treatment, of the underlying mechanisms and network abnormalities producing symptoms of schizophrenia.Frontiers in Human Neuroscience 03/2015; 9:134. DOI:10.3389/fnhum.2015.00134 · 2.90 Impact Factor
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ABSTRACT: Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital–cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH.01/2014; 6. DOI:10.1016/j.nicl.2014.08.027
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ABSTRACT: Aim of the study. Investigation of relationship between cerebellar motor dysfunctions and language im-pairments connected with cerebellum during phonological and semantic fluency tasks and verb genera-tion task in schizophrenic patients and healthy control group. Subject or material and methods. 14 schizophrenic patients on olanzapine, clozapine or quetiapine treat-ment and 13 healthy volunteers were examined. Motor signs were assessed by using the International Co-operative Ataxia Rating Scale (ICARS). Phonological and semantic fluency tasks were performed. All of the words were recorded and counted. Results. Patients with schizophrenia revealed significantly higher ICARS mean score (12.21) than control group (3.92), and lower number of proper generated words in semantic fluency and verb generation tasks. Strong negative correlation (rs(13) = -0.71, p<0.01) was found between ICARS total score and number of proper answers in verb generation task. Discussion. Higher number of total ICARS score in schizophrenia patients in comparison to control group may suggest cerebellar impairments. There is disproportion between semantic and phonological fluency. Significant correlation between verb generation and cerebellar signs supports a hypothesis of cerebellum dysfunction during this task in schizophrenia patients. Conclusions. Schizophrenic patients reveal impairments which may be connected with the cerebellum. schizophrenia / verb generation / cerebellum / cognitive dysmetriaArchives of Psychiatry and Psychotherapy 09/2013; 3:11-17. DOI:10.12740/APP/18821