Abnormal neural functions associated with motor inhibition deficits in schizophrenia and bipolar disorder

Abstract

Deficits in response inhibition have been observed in schizophrenia and bipolar disorder; however, the neural origins of the abnormalities and their relevance to genetic liability for psychosis are unknown. We used a stop‐signal task to examine motor inhibition and associated neural processes in schizophrenia patients (n = 57), bipolar disorder patients (n = 21), first‐degree biological relatives of patients with schizophrenia (n = 34), and healthy controls (n = 56). Schizophrenia patients demonstrated motor control deficits reflected in longer stop‐signal reaction times and elongated reaction times. With the possibility of needing to inhibit a button press, both schizophrenia and bipolar disorder patients showed diminished reductions of the P300 brain response and only the healthy controls demonstrated adjustments in response execution time, as measured by response‐locked lateralized readiness potentials. Schizotypal traits in the biological relatives were associated with less P300 modulation consistent with the motor‐related anomalies being associated with subtle schizophrenia‐spectrum symptomatology in family members. The two patient groups had elongated response selection processes as manifest in the delayed onset of the stimulus‐locked lateralized readiness potential. The bipolar disorder group was unique in showing significantly diminished neural responses to the stop‐signal to inhibit a response. Antipsychotic medication dosage was related to worse motor inhibition, thus motor inhibition deficits in schizophrenia may be partially explained by the effect of pharmacological agents. Failed modulation of brain processes in relation to response inhibition probability and the lengthening of motor response selection appear to be transdiagnostic abnormalities spanning schizophrenia and bipolar disorder.

Exploring the Relationship of Transdiagnostic Mood and Psychosis Symptom Domains with Motor Dysfunction

“…Movement fluidity data from the participants with bipolar I disorder have not been previously published. The participants with LRP data in this study are subsamples of the schizophrenia/schizoaffective disorder, depressive type, bipolar disorder, relative, and control samples reported in Van Voorhis et al [51], and reflect participants for whom both LRP and movement fluidity data were available. LRP data from individuals with schizoaffective disorder, bipolar type and an additional 6 relatives have not been previously published.…”

“…Similarly, we are conducting a secondary analysis of LRP data for the current study. Data were collected as a part of a stop signal task (SST) paradigm, which was used to investigate the neural correlates of motor inhibition [51]. The SST comprised a Go Only condition and a Go/Stop condition.…”

“…Additional task details and full description of EEG data collection, processing, and analysis are provided in Van Voorhis et al [51]. Briefly, EEG data were collected with either a 64-or 128-channel Ag/AgCl electrode array and a Biosemi ActiveTwo system (1,024 Hz sampling rate, single earlobe reference signal).…”

“…Several studies have reported S-LRP onset latency delays in schizophrenia [46][47][48][49], while the literature examining R-LRP onset latency in schizophrenia has been mixed [46][47][48][49][50]. Here again, we are conducting a secondary analysis on data that we have previously published [51]. In Van Voorhis et al [51], we reported significantly later S-LRP onset latency in both (1) individuals with schizophrenia or schizoaffective disorder and (2) individuals with bipolar disorder compared to first-degree relatives of individuals with a psychotic disorder, but not DOI: 10.1159/000503928 controls; there were no differences between groups in R-LRP onset latency.…”

“…Here again, we are conducting a secondary analysis on data that we have previously published [51]. In Van Voorhis et al [51], we reported significantly later S-LRP onset latency in both (1) individuals with schizophrenia or schizoaffective disorder and (2) individuals with bipolar disorder compared to first-degree relatives of individuals with a psychotic disorder, but not DOI: 10.1159/000503928 controls; there were no differences between groups in R-LRP onset latency. We do not have any specific hypotheses regarding which symptoms will be associated with variance in S-LRP onset latency, however given that relatives and controls were not significantly different from each other in Van Voorhis et al [51], we hypothesize that subthreshold psychotic symptomology will be associated with S-LRP onset latency in these groups (i.e., any attenuated abnormality might only show up in individuals displaying some degree of subthreshold symptoms).…”