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: 12.3). 07/2005; 162(6):1203-5. DOI: 10.1176/appi.ajp.162.6.1203
Source: PubMed


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.
    Full-text · Article · Dec 2014 · Clinical neuroimaging
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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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    ABSTRACT: Background: Transcranial magnetic stimulation (TMS) has been used in both physiological studies and, more recently, the therapy of Parkinson's disease (PD). Prior TMS studies in healthy subjects and other patient populations demonstrate a slight risk of seizures and other adverse events. Our goal was to estimate these risks and document other safety concerns specific to PD patients. Methods: We performed an English-Language literature search through PudMed to review all TMS studies involving PD patients. We documented any seizures or other adverse events associated with these studies. Crude risks were calculated per subject and per session of TMS. Results: We identified 84 single pulse (spTMS) and/or paired-pulse (ppTMS) TMS studies involving 1091 patients and 77 repetitive TMS (rTMS) studies involving 1137 patients. Risk of adverse events was low in all protocols. spTMS and ppTMS risk per patient for any adverse event was 0.0018 (95% CI: 0.0002-0.0066) per patient and no seizures were encountered. Risk of an adverse event from rTMS was 0.040 (95% CI: 0.029-0.053) per patient and no seizures were reported. Other adverse events included transient headaches, scalp pain, tinnitus, nausea, increase in pre-existing pain, and muscle jerks. Transient worsening of Parkinsonian symptoms was noted in one study involving rTMS of the supplementary motor area (SMA). Conclusion: We conclude that current TMS and rTMS protocols do not pose significant risks to PD patients. We would recommend that TMS users in this population follow the most recent safety guidelines but do not warrant additional precautions.
    Full-text · Article · Mar 2013 · Parkinsonism & Related Disorders
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    • "There are many findings that show cerebellar abnormalities in schizophrenia. Cerebellar inhibition of the motor cortex assessed by TMS is decreased in schizophrenia [22]. Reduction of cerebellar-dependent delay eyeblink conditioning [23] reflects impaired cerebellar time processing in schizophrenia. "
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    ABSTRACT: Abnormal execution of several movements in a sequence is a frequent finding in schizophrenia. Successful performance of such motor acts requires correct integration of cortico-subcortical processes, particularly those related to cerebellar functions. Abnormal connectivity between cortical and cerebellar regions with resulting cognitive dysmetria has been proposed as the core dysfunction behind many signs and symptoms of schizophrenia. The aim of the present study was to assess if these proposed abnormalities in connectivity are a unifying feature of schizophrenia, or, rather, reflect a specific symptom domain of a heterogeneous disease. We predicted that abnormal functional connectivity between the motor cortex and cerebellum would be linked with abnormal performance of movement sequencing. We examined 24 schizophrenia patients (SCH) and 24 age-, sex-, and handedness-matched healthy controls (HC) using fMRI during a modified finger-tapping task. The ability to perform movement sequencing was tested using the Neurological Evaluation Scale (NES). The subjects were categorized into two groups, with (SQ+) and without (SQ-) movement sequencing abnormalities, according to the NES-SQ score. The effects of diagnosis and movement sequencing abnormalities on the functional connectivity parameters between the motor cortex and cerebellum (MC-CRBL) and the supplementary motor cortex and cerebellum (SMA-CRBL) activated during the motor task were analyzed. We found no effect of diagnosis on the functional connectivity measures. There was, however, a significant effect on the SQ group: SQ + patients showed a lower level of MC-CRBL connectivity than SQ- patients and healthy controls. Moreover, the level of MC-CRBL and SMA-CRBL negatively correlated with the magnitude of NES-SQ abnormalities, but with no other NES domain. Abnormal cortico-cerebellar functional connectivity during the execution of a motor task is linked with movement sequencing abnormalities in schizophrenia, but not with the diagnosis of schizophrenia per se. It seems that specific patterns of inter-regional connectivity are linked with corresponding signs and symptoms of clinically heterogeneous conditions such as schizophrenia.
    Full-text · Article · Mar 2012 · BMC Psychiatry
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