Dysfunctional neural plasticity in patients with schizophrenia

Abstract

Context: Neural plasticity in the human cortex involves a reorganization of synaptic connections in an effort to adapt to a changing environment. In schizophrenia, dysfunctional neural plasticity has been proposed as a key pathophysiological mechanism.

Objective: To evaluate neural plasticity in unmedicated and medicated patients with schizophrenia compared with healthy subjects.

Design: Neural plasticity can be evaluated from the motor cortex in healthy subjects using transcranial magnetic stimulation through a paradigm known as use-dependent plasticity. This paradigm involves several steps: (1) measuring the spontaneous direction of transcranial magnetic stimulation-induced thumb movements; (2) training subjects to practice thumb movements opposite to this baseline direction for 30 minutes; and (3) measuring the direction of transcranial magnetic stimulation-induced thumb movement after training. Previous experiments have shown that in healthy subjects, posttraining transcranial magnetic stimulation-induced movements occur in a vector commensurate with the practiced movements, which may be associated with time-limited reorganization of motor circuits.

Setting: All of the participants were recruited and evaluated at the Centre for Addiction and Mental Health.

Participants: Fourteen medicated and 6 unmedicated patients with schizophrenia and 20 healthy subjects were recruited.

Main outcome measure: It was anticipated that patients with schizophrenia would demonstrate attenuated motor reorganization in the direction of training.

Results: Both medicated and unmedicated patients with schizophrenia demonstrated significantly reduced motor reorganization compared with healthy subjects.

Conclusions: It is possible that in schizophrenia, these deficits in neural plasticity are related to disturbances of gamma-aminobutyric acid, N-methyl-D-aspartate neurotransmission, or dopamine that may potentially account for the aberrant motor performance of these patients.