Abstract
Background Impaired inhibition has been reported in patients with schizophrenia in a variety of cognitive and motor tasks. Recent transcranial magnetic stimulation studies performed during rest show reduced cortical inhibition in primary motor cortex (M1) at rest in schizophrenia patients, supporting the hypothesis of impaired GABA-ergic inhibition as an underlying mechanism. However, cortical excitability and intracortical inhibition in M1 are highly task-dependent, for example, inhibiting a planned motor response leads to reduced excitability and enhanced intracortical inhibition. Studies on task-dependent cortical excitability and inhibition are lacking in schizophrenia. The aim of this study was therefore to investigate cortical excitability and intracortical inhibition during voluntary motor inhibition in patients with schizophrenia. Methods 25 stabilized patients with schizophrenia (DSMIV) and a group of 23 age-comparable healthy volunteers were included. We used a modified version of the Go–Stop task to study voluntary motor inhibition. This task consisted of moving the index finger in response to Go and Stop signals. In 30% of trials the subject received a visual cue to inhibit the prepared finger lift. Paired-pulse transcranial magnetic stimulation (TMS) was used to measure M1 excitability and short-latency intracortical inhibition (SICI%) during three phases of the task: (i) early without movement preparation (Early); (ii) late with preparation of finger lift (Late prep ); and (iii) late with inhibition of finger lift (Late inhib ). Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle. Results Patients and control subjects performed equally on the voluntary inhibition task, with similar stop signal reaction times (mean SSRT controls 189 ± 21 ms and patients 186 ± 31 ms, P = 0.6). TMS at rest revealed similar resting and active motor thresholds in patients and controls (P > 0.9). The cortical silent period was shorter in the patients but did not differ significantly (mean controls 162 ± 30 ms and patients 147 ± 61 ms, P = 0.36). During the Go–Stop task, cortical excitability was similar in patients and controls with a task-dependent modulation of MEPs (mean RMS MEPs: Early = 477 μV, Late prep = 854 μV, and Late inhib = 531 μV; effect of Phase, P F = 4.5, P = 0.02) with posthoc comparisons revealing a significant reduction in the Late inhib phase in patients compared to controls ( P = 0.02). In patients the SICI% during Late inhib correlated negatively with SSRT ( R = − 0.72, P inhib had longer SSRT. Conclusions To our knowledge this is the first study on task-dependent modulation of cortical excitability and intracortical inhibition in patients with schizophrenia. We show that patients with schizophrenia have reduced SICI during voluntary inhibition of a prepared finger lift. Surprisingly, there were no differences found in task performance or in MEP amplitudes during the task. These findings show that schizophrenia patients are capable of inhibiting motor tasks despite having reduced intracortical inhibition. This suggests the use of compensatory mechanisms in voluntary motor inhibition in stabilized schizophrenia patients.
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