Article

Reduced Cerebellar Inhibition in Schizophrenia: A Preliminary Study

Schizophrenia Program, Centre for Addiction and Mental Health, University of Toronto, Ont. M5T 1R8, Canada.
American Journal of Psychiatry (Impact Factor: 13.56). 07/2005; 162(6):1203-5. DOI: 10.1176/appi.ajp.162.6.1203
Source: PubMed

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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    • "According to the " cognitive dysmetria " or " dysmetria of thought " models of schizophrenia, aberrant cerebellar modulation of information to the cerebral cortex is involved in the pathophysiology of the disorder (Andreasen et al., 1998; Schmahmann, 1998a). This finding is consistent with the Daskalakis et al. (2005) study, which preliminarily reported that, compared with controls, patients with schizophrenia demonstrated deficits in cerebellar inhibition. Their data are corroborated by our results demonstrating between-group differences in the causal flow of information between the cerebellar–occipital component and other regions , with an afferent direction of flow for the controls (Figs. "
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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.
    12/2014; 6. DOI:10.1016/j.nicl.2014.08.027
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    • "However, more severe adverse effects may include mood changes (induction of mania), scalp burns from electrodes, and induction of seizures [2]. Seizures during TMS are thought to be a result of cortical pyramidal cell activation, spread of excitation to neighboring neurons, and overwhelming of inhibitory mechanisms [13]. Although reviews detailing the safety of TMS use exist for depression, epilepsy, and migraine, no such review exists for TMS use in PD [8] [14] [15]. "
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    • "Another method of assessing cortical inhibition is through electromyography (EMG) measurements of voluntary tonic motor activity suppression after a TMS pulse to the contralateral primary motor cortex, and this method has also revealed deficits in patients with psychosis (Daskalakis et al., 2002; Fitzgerald et al., 2002a; Wobrock et al., 2009). Although only indirectly related to the motor cortices, TMS paradigms that putatively gauge transcallosal inhibition have also suggested aberrant inhibitory function in subjects with psychotic symptoms (Daskalakis et al., 2002; Fitzgerald et al., 2002b), and a preliminary study by Daskalakis et al. (2005) has indicated that cerebellar inhibition is also reduced in patients with schizophreniform psychoses. The paradigm for assessing cerebellar inhibition putatively activates Purkinje cells, leading to a decrease of the excitatory drive from the dentate and interpositus nuclei to the motor cortex via the thalamus (Ugawa et al., 1995). "
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