The relation of the change in symptoms and cognitive functions with the change in cortical inhibition parameters measured by transcranial magnetic stimulation: An eight-week follow-up study

Abstract

Previous transcranial magnetic stimulation (TMS) studies have demonstrated cortical inhibition (CI) abnormalities in patients with schizophrenia. However, the relationship between changes in CI and changes in psychopathology and cognition resulting from antipsychotic treatment is not known. This is an 8 week follow up study which aims to evaluate the relation of the CI with the symptoms and cognitive functions of the patients who are switched to new atypical antipsychotic treatment, and to compare the TMS measurements of patients with those of controls. Method: Thirteen patients and 13 control subjects matched according to age, sex, and educational level were included in the study. Patients were assessed with TMS, Positive and Negative Syndrome Scale (PANSS), and a neurocognitive battery at baseline and at 8 weeks post-treatment, while the control group was evaluated with the neurocognitive battery and TMS at baseline only. CI parameters evaluated by TMS include resting motor threshold, cortical silent period, ipsilateral silent period (ISP), short interval intracortical inhibition (SICI) and intracortical facilitation. Results: Intracortical facilitation (ICF) was weaker and ISP was longer in patients relative to control subjects both at baseline and at the end of the eight weeks. Intracortical facilitation decreased following 8 weeks of antipsychotic treatment, indicating an increase in CI. The decrease in PANSS general psychopathology score was directly correlated with the decrease in ICF. SICI positively correlated with cognitive test performance in both cross-sectional and longitudinal analyses. Conclusion: Our findings suggest that increase in CI is associated with the improvement in the symptoms and the action of the atypical antipsychotics.

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

“…Tang and colleagues 54 found that a higher negative symptom score was associated with a lower ICF among medicated patients with schizophrenia, but they concluded that this relationship needed further investigation. In another study, 90 a reduction in ICF (interstimulus interval = 7 ms) was associated with a reduction in scores on the PANSS general psychopathology subscale in a group of patients with moderate positive symptoms after 8 weeks of treatment with an atypical antipsychotic. According to the authors, this result may have been because of an increase in cortical inhibition after antipsychotic treatment.…”

“…Reports have indicated that CSP duration is increased in patients treated with clozapine compared to healthy controls, unmedicated patients and patients treated with other antipsychotics. 87,131 Further, Kaster and colleagues 95 also found that 6 weeks of clozapine treatment increased the CSP duration in patients with medication resistance, and Yildiz and colleagues 90 showed that 8 weeks of clozapine treatment increased the CSP duration in 6 patients with moderate positive symptoms compared to healthy controls. Taken together, these results suggest that the therapeutic effect of clozapine may be in part through GABA-B receptor-mediated inhibition.…”

“…Clozapine has not been demonstrated to alter RMT, MEP size (in response to suprathreshold single-pulse stimuli), SICI or ICF, 87,90,95,131 although Yildiz and colleagues 90 reported decreased ICF after 8 weeks of clozapine treatment. Risperidone had no effect on RMT, SICI or ICF after 4 weeks of treatment 132 or compared to healthy controls.…”

“…In 15 of the 19, no significant differences in RMT were reported between patients and healthy controls. 54,60,[78][79][80][81][82][83][84][85][86][87][88][89][90] This lack of difference in RMT was observed in patients with chronic schizophrenia but also extended to medication-naive or minimally treated (< 1 month) patients with first-episode psychosis. 91 Lower RMT values (indicating increased corticospinal excitability) were reported in only 1 study of medicated patients with schizophrenia, but also in patients with major depressive disorder and manic disorder.…”

“…Resting motor threshold Fifteen studies reported no significant differences between medicated patients with chronic schizophrenia and healthy controls; 54,60,[78][79][80][81][82][83][84][85][86][87][88][89][90] 1 study 91 reported no significant difference between medication-naive or minimally treated (< 1 month) patients with first-episode psychosis and healthy controls; 1 study reported lower RMT in medicated patients; 92 2 studies reported higher RMT in medicated patients with chronic schizophrenia; 93,94 1 study showed higher RMT in medicated patients 45 Patients would show deficits in GABA-mediated cortical inhibition as measured by CSP and pairedpulse inhibition paradigms (e.g., SICI and LICI). Intracortical facilitation may not be significantly different between patients and healthy controls Active motor threshold Two studies reported no significant differences between patients with chronic schizophrenia (mostly medicated) and healthy controls 84,86 or healthy siblings 86 Amplitude of motor evoked potentials Four studies found no significant differences between medicated and unmedicated patients with chronic schizophrenia and healthy controls; 81,82,87,94 2 studies reported unaltered MEP sizes in medicated patients with first-episode schizophrenia 58 and medicated patients; 89 1 study found smaller MEP sizes in medicated chronic patients; 54 1 study found increased MEP sizes in medicated patients with chronic schizophrenia; 88 1 study found no significant differences between patients with recent-onset and multi-episode schizophrenia, people at risk and healthy controls; 1 study found smaller MEP sizes in people at risk compared to patients with first-episode schizophrenia and healthy controls 45 Duration of cortical silent period Four studies found no significant differences between medicated patients with chronic schi...…”