Disrupted Central Inhibition after Transcranial Magnetic Stimulation of Motor Cortex in Schizophrenia with Long-Term Antipsychotic Treatment

Abstract

Aims. Schizophrenia is a neuropsychiatric disorder associated with mental and motor disturbances. We aimed to investigate motor control, especially central silent period (CSP) in subjects with schizophrenia (n = 11) on long-term antipsychotic treatment compared to healthy controls (n = 9). Methods. Latency and duration of motor evoked potentials (MEPs) and CSPs were measured with the help of single pulse transcranial magnetic stimulation (TMS) and intramuscular electrodes. After stimulation of the dominant and nondominant motor cortex of abductor digiti minimi (ADM) and tibialis anterior (TA) muscle areas, respective responses were measured on the contralateral side. Results. MEPs did not differ significantly between the groups. Multiple CSPs were found predominantly in subjects with schizophrenia, which showed a higher number of CSPs in the dominant ADM and the longest summarized duration of CSPs in the nondominant ADM (P < 0.05) compared to controls. Conclusions. There were multiple CSPs predominantly in the upper extremities and in the dominant body side in subjects with schizophrenia. Behind multiple CSPs may lie an impaired regulation of excitatory or inhibitory neurotransmitter systems in central motor pathways. Further research is needed to clarify the role of the intramuscular recording methods and the effect of antipsychotics on the results.

A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia

“…Finally, 7 studies examined the relationship between TMSevoked muscular responses and medication dose in patients. 58,60,84,89,100,104,129 No significant correlation was reported between antipsychotic dose and RMT, AMT, MEP amplitude elicited by single suprathreshold stimuli, CSP duration or left dorsal premotor-right motor facilitatory connectivity. 58,84,89,100,104,129 Further, the degree of SICI and ICF was not related to the dose of antipsychotics 58,84,89 or benzodiazepines.…”

“…In contrast, Daskalakis and colleagues 130 showed increased CSP duration in medicated patients compared to unmedicated patients, and similar CSP duration between medicated patients and healthy controls. Further, Ahlgren-Rimpilainen and colleagues 100 found that in the nondominant extremities (i.e., the nondominant hemisphere, abductor digiti minimi and tibialis anterior muscles), patients who were taking conventional antipsychotics had shorter mean first and total CSP duration compared to healthy controls and patients who were taking atypical antipsychotics; those taking atypical antipsychotics had the longest mean first and total CSP durations. According to the authors, 100 these findings were in line with the assumption that clozapine, which is an atypical antipsychotic, may normalize or even lengthen reduced central inhibition in schizophrenia.…”

“…One study applied biphasic TMS pulses over both motor cortices with an intensity of 60% to 80% of maximal stimulator output (above the RMT). 100 The responses were recorded from the abductor digiti minimi muscles in the upper extremities and tibialis anterior muscles in the lower extremities, using needle electrodes inserted into the muscles. The authors observed multiple CSPs in single trials, predominantly in patients with chronic schizophrenia who had been hospitalized and on long-term antipsychotic treatment (averages of 22.5 and 11 years for those on conventional and atypical antipsychotics, respectively).…”

Assessment of Cortical Plasticity in Schizophrenia by Transcranial Magnetic Stimulation

“…If the interstimulus interval between the 2 pulses is long, i.e., 9-25 ms, a facilitatory effect is observed, referred to as intracortical facilitation (ICF) [ 40 , 43 , 45 – 56 ]. ICF can constitute more facilitation and weaker inhibition.…”

“…A previously early study, on the CSP in schizophrenia, revealed no significant differences in the duration of CSP between schizophrenic patients and controls [ 46 ]. However, a longer initial latency (onset latency) in treated patients was recorded [ 45 , 56 , 69 ]. Multiple studies reported a consistent shorter CSP in patients without medication effects (risperidone and olanzapine) [ 34 , 39 , 52 , 70 , 71 ].…”