Impaired long-term depression in schizophrenia: A cathodal tDCS pilot study

Abstract

Neural plasticity involves the reorganization of synaptic connections and represents the ability of the brain to adjust its function in response to challenge. Disturbed cortical plasticity has been linked to the pathophysiology of schizophrenia, with indirect evidence for disturbed plasticity in the disease state having been provided by postmortem studies and various animal models. However, glutamate-dependent long-term depression (LTD)-like cortical plasticity has not yet been investigated. To investigate LTD-like cortical plasticity after transcranial direct current stimulation (tDCS) in schizophrenia patients. Using excitability-diminishing cathodal tDCS, we performed the first invivo assessment of glutamate-dependent LTD-like cortical plasticity in 21 schizophrenia patients and 21 matched healthy control subjects. To reveal the physiologic basis of the hypothesized plasticity deficits, we tested different inhibitory and excitatory neuronal circuits with transcranial magnetic stimulation (TMS). Cathodal tDCS failed to reduce motor-evoked potential amplitudes in schizophrenia patients, indicating abolished LTD-like plasticity. Furthermore, schizophrenia patients had a prolonged GABA(B)-dependent cortical silent period (CSP) at baseline and tDCS failed to modulate the duration of CSP in the patient group. Finally, schizophrenia patients presented an elevated resting-motor threshold at baseline in comparison to healthy controls. The pattern of our results provides evidence for a specific plasticity deficit in schizophrenia patients, which might be associated with a hyperglutamatergic state. These findings may reflect a reduced signal-to-noise ratio and a disturbed filter function in schizophrenia patients. An increase of GABA(B)-activity may be a compensatory mechanism to dysfunctional LTD-like plasticity in schizophrenia.