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Dysfunctional neural plasticity in patients with schizophrenia
Zafiris J Daskalakis1, Bruce K Christensen, Paul B Fitzgerald
1Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. jeff_daskalakis@camh.net
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.
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