Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation

Behav Brain Res. 2011 Oct 10;224(1):15-22. doi: 10.1016/j.bbr.2011.05.017. Epub 2011 May 30.


Neural and cortical plasticity represent the ability of the brain to reorganize its function in response to a challenge. Plasticity involves changing synaptic activity and connectivity. Long-term-potentiation is one important mechanism underlying these synaptic changes. Disturbed neuronal plasticity is considered to be part of the pathophysiology of schizophrenia and has been linked to the different clinical features of this severe illness. The aim of the present study was to investigate nonfocal cortical plasticity and cortical excitability in recent-onset and multi-episode schizophrenia compared with healthy subjects. Nonfocal cortical plasticity can be induced in the motor cortex of healthy subjects with anodal transcranial direct current stimulation. Animal and human research indicates that this long-term-potentiation-like plasticity is glutamate-dependent and that these plasticity shifts can last for several hours. Transcranial direct current stimulation-induced plasticity was monitored by transcranial magnetic stimulation-generated motor evoked potentials. Well-characterized transcranial magnetic stimulation protocols were applied to determine the physiological basis of plasticity changes. Multi-episode schizophrenia patients showed significantly reduced long-term-potentiation-like plasticity compared to recent-onset schizophrenia patients and healthy controls. All schizophrenia patients demonstrated reduced cortical inhibition. Our results indicate that the long-term-potentiation-like plasticity deficit in schizophrenia patients is related to the disease course. Disturbances of N-methyl-d-aspartate, gamma-aminobutyric acid and dopamine receptors may account for this plasticity deficit. LTP-like plasticity deficits might be related to disturbed information processing in schizophrenia patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Antipsychotic Agents / therapeutic use
  • Case-Control Studies
  • Chi-Square Distribution
  • Electromyography
  • Evoked Potentials, Motor / physiology*
  • Female
  • Humans
  • Long-Term Potentiation / physiology*
  • Male
  • Middle Aged
  • Motor Cortex / physiopathology*
  • Reaction Time / physiology
  • Schizophrenia, Paranoid / drug therapy
  • Schizophrenia, Paranoid / pathology*
  • Transcranial Magnetic Stimulation / methods*


  • Antipsychotic Agents