Evidence for Impaired Long-Term Potentiation in Schizophrenia and Its Relationship to Motor Skill Leaning

Abstract

Several lines of evidence suggest that schizophrenia (SCZ) is associated with disrupted plasticity in the cortex. However, there is little direct neurophysiological evidence of aberrant long-term potentiation (LTP)-like plasticity in SCZ and little human evidence to establish a link between LTP to learning and memory. LTP was evaluated using a neurophysiological paradigm referred to as paired associative stimulation (PAS). PAS involves pairing of median nerve electric stimulation with transcranial magnetic stimulation (TMS) over the contralateral motor cortex (for abductor pollicis brevis muscle activation) delivered at 25-ms interstimulus interval. This pairing was delivered at a frequency of 0.1 Hz for 30 min. LTP was reflected by the change in motor evoked potentials (MEPs) before and after PAS. In addition, motor skill learning was assessed using the rotary pursuit task. Compared with healthy subjects, patients with SCZ demonstrated significant MEP facilitation deficits following PAS and impaired rotary-pursuit motor learning. Across all subjects there was a significant association between LTP and motor skill learning. These data provide evidence for disrupted LTP in SCZ, whereas the association between LTP with motor skill learning suggests that the deficits in learning and memory in SCZ may be mediated through disordered LTP.