Prefrontal Cortical Engagement Through Non-Invasive Brain Stimulation in Schizophrenia
Condition: Schizophrenia; Psychosis
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      Cognitive impairments in schizophrenia are the most debilitating aspect of the illness and
      poorly treated by current medications. This study investigates transcranial direct current
      stimulation (tDCS) - a safe, noninvasive weak electrical current delivery to stimulate brain
      function - as a novel therapeutic for cognition in schizophrenia. Integrating
      neurostimulation, electrophysiology and neuroimaging, this project aims to study tDCS effects
      on cognition by verifying therapeutic target engagement, evaluating the tolerability of tDCS
      sessions, and optimizing treatment parameters.
    

Detailed description: 
      Cognitive deficits are a strong predictor of functional outcome in schizophrenia, yet poorly
      remediated by current treatments. Disturbances in dorsolateral prefrontal cortex (DLPFC)
      function underlie core impairments such as in cognitive control and thus represent a critical
      target for novel therapeutics. Initial studies indicate transcranial direct-current
      stimulation (tDCS) may be effective in reducing symptoms due to DLPFC dysfunction. While tDCS
      potentially represents an exciting, novel therapeutic advance, a number of basic questions
      should be addressed prior to conducting larger-scale clinical trials, including: verifying
      therapeutic target engagement, optimizing treatment parameters, and evaluating for meaningful
      clinical effects. Recent studies employing tDCS to enhance prefrontal cortical function in
      schizophrenia applied stimulating electrodes over the left frontal scalp region, putatively
      targeting the left DLPFC. However, explicit confirmation of such target engagement is
      lacking. Further, EEG studies have demonstrated close links of frontal cortical gamma
      oscillations to cognitive control processes but modulation of this critical physiologic
      process has not been investigated. Accordingly, the primary aim of this study is to employ
      multimodal imaging to explicitly test for the assumed DLPFC engagement (fMRI) and modulation
      of frontal gamma activity (EEG) by tDCS. This study will also investigate the optimization of
      tDCS application parameters. Analogous to dose-finding investigations in drug studies, we
      will conduct a parametric investigation of optimal current strengths. Also, while there is
      extensive evidence for tolerability of single session tDCS, confirmation of feasibility of
      multisession optimized protocols in schizophrenia is lacking and so will be explicitly
      evaluated.

      In summary, a successful outcome of this study would provide tDCS the sound mechanistic and
      methodologic basis for more definitive testing in large-scale clinical trials as a highly
      innovative therapeutic intervention for cognitive impairments in schizophrenia.
    

Intervention name(s): transcranial direct current stimulation
Intervention type(s): Device
Intervention description(s): transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: tDCS; cognitive control; EEG; gamma oscillations