title: Differential response to anodal tDCS and PAS is indicative of impaired focal LTP-like plasticity in schizophrenia.
abstract: Increasing evidence suggests that neural plasticity impairments, observed in schizophrenia patients, are driven by dysfunctional integration of neural signaling. However, what is less clear is whether this impairment is resultant from a general deficit in plastic induction or whether a specific plastic mechanism is affected. In the current study we aimed to assess whether schizophrenia has a selective impact on focal or non-focal plasticity induction. To pursue this goal we utilized two non-invasive stimulation techniques that differ in the mechanism of long-term potentiation (LTP)-like plasticity induction: focal paired associative stimulation (PAS) and non-focal anodal transcranial direct current stimulation (a-tDCS). 20 schizophrenia patients and 20 matched healthy controls received PAS and a-tDCS in two separate sessions. Cortical excitability and cortical plasticity were assessed by transcranial magnetic stimulation (TMS)-elicited motor evoked potentials (MEP). In both study groups, non-focal a-tDCS resulted in a significant increase of mean MEP magnitude indicating the successful induction of non-focal LTP-like plasticity. In contrast, an increase in mean MEP magnitude following PAS was only observed in the control group, suggesting impaired focal LTP-like plasticity in schizophrenia. Additionally, we observed significantly impaired short-latency intracortical inhibition (SICI) in schizophrenia. This is the first study to comparatively evaluate non-focal and focal plasticity mechanisms in schizophrenia patients. The differential patterns of LTP-like plasticity responses indicate that reduced plasticity in schizophrenia could be ascribed to impairments in spatially and temporally restricted signal integration. This impairment, coupled with an observed reduction of inhibitory circuit efficacy, might further contribute to impairments in coordinating focal signals.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximillian University, Nußbaumstr. 7, D-80336 Munich, Germany. Electronic address: wolfgang.strube@med.uni-muenchen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Strube
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximillian University, Nußbaumstr. 7, D-80336 Munich, Germany. Electronic address: tilmann.bunse@med.uni-muenchen.de.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Bunse
authors.affiliation: Department of Neurology, University Medical Hospital Bergmannsheil, Bürkle de la Camp-Platz 1, D-44789 Bochum, Germany,; Leibniz Research Centre for Working Environment and Human Factors TU Dortmund, Ardeystr. 67, D-44139 Dortmund, Germany. Electronic address: mnitsch1@gwdg.de.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nitsche
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximillian University, Nußbaumstr. 7, D-80336 Munich, Germany. Electronic address: ulrich.palm@med.uni-muenchen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Palm
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximillian University, Nußbaumstr. 7, D-80336 Munich, Germany. Electronic address: peter.falkai@med.uni-muenchen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximillian University, Nußbaumstr. 7, D-80336 Munich, Germany. Electronic address: alkomiet.hasan@med.uni-muenchen.de.
authors.forename: Alkomiet
authors.initials: A
authors.lastname: Hasan
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology*; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000503:physiopathology*; D065908:Transcranial Direct Current Stimulation; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
keywords: Anodal transcranial direct current stimulation (tDCS); Focality; Like plasticity; Long term potentiation (LTP); Paired associative stimulation (PAS); Schizophrenia; Transcranial magnetic stimulation (TMS)