Optimizing the effects of transcranial direct current stimulation (tDCS) for the treatment of psychiatric diseases

Principal Investigator: Michael A. Nitsche (Dortmund)

 

Background and aims


tDCS is a non-invasive brain stimulation tool which induces enduring stimulation polarity-dependent alterations of cortical excitability. Numerous psychiatric diseases have been associated with pathological alterations of cortical excitability, and activity, and tDCS has some therapeutic effects. However, its efficacy is limited, probably due to sub-optimal tDCS protocols. We will determine if adjustment of stimulation parameters can enhance strength, and duration of effects. First we will optimize stimulation intensity, duration, repetition rate, and adjunctive medication, for the model of the motor cortex in healthy humans. Second, we will transfer the results to the prefrontal cortex, a target structure for stimulation in psychiatric diseases. Finally, we will explore the translation of the effects to psychiatric patients, and animal models of psychiatric diseases, in cooperation with the Clinical partners of Modules B/C. Primary endpoint will be the definition of tDCS protocols suited to induce long-lasting, clinically relevant alterations of cortical excitability in psychiatric patients. This will be crucial for the definition of optimal clinical treatment protocols envisaged in Module C.

 

Working hypothesis


Pathophysiological alterations of cortical excitability are involved in many psychiatric diseases. Non-invasive brain stimulation, including tDCS, has been probed to ameliorate symptoms by antagonising these. So far, effects are modest, probably due to suboptimal stimulation protocols. We hypothesize that the key for enhancing the efficacy of tDCS for clinical treatment is enhancing duration, and magnitude of excitability alterations via adjustment of stimulation parameters, taking into account the specific target area, and disease-related, state-dependent physiology.

 

Research questions


  1. Can tDCS-induced excitability alterations be increased by optimizing stimulation parameters, are these effects state-dependent, and what are the physiological foundations?
  2. To which degree do optimized protocols obtained in the primary motor cortex translate to the prefrontal cortex, the target for clinical effects of tDCS, at rest and during task performance?
  3. Are the physiological effects obtained via tDCS in healthy subjects transferable to patients with regard to physiological, and clinical effects?

The impact of gender on tDCS effects will be taken into account (equal number of males and females in all experiments, for secondary analysis). Side effects of stimulation protocols will be systematically explored in all studies.