Dysfunctional neural plasticity in patients with schizophrenia.

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.