Disorder-tailored transcranial direct current stimulation (tDCS) of the prefrontal cortex

Principal Investigator: Frank Padberg (Munich), Daniel Keeser (Munich)

 

Background and aims


Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) is currently investigated as therapeutic brain stimulation (BS) approach in major depressive (MDD) and anxiety disorders. In both conditions, different subregions of the PFC (e.g. the dorsolateral prefrontal cortex [DLPFC], the dorsomedial prefrontal cortex [DMPFC] and others) are critically involved in their respective pathophysiology. Although the neurophysiological properties of tDCS have been extensively investigated at the motor cortex level, the action of PFC tDCS on resting state and functional connectivity of neural networks is largely unexplored. Moreover, it has not been investigated to date whether and how such effects of PFC tDCS on connectivity are state-depended and may differ between health and disease. Thus, WP5 aims at studying the interaction of BS and brain connectivity applying resting state fMRI, activation paradigms and combined fMRI/EEG measures. Different prefrontal tDCS protocols will be investigated in healthy subjects, MDD and phobia patients during anticipatory anxiety as paradigmatic pathological conditions. WP5 is expected to generate a model for PFC tDCS modulating functional connectivity in different conditions to provide tailored tDCS protocols for clinical efficacy studies in MDD and anxiety disorders (forward translation). Moreover, WP5 will inform other preclinical WPs regarding the functional neuroanatomy of prefrontal tDCS (reverse translation).

 

Working hypothesis


Revealing the action of PFC tDCS on brain physiology in health and pathological conditions is crucial for the development of its targeted and individualized therapeutic application. The strength and direction of tDCS effects on brain connectivity depend on the prior activation state of defined PFC subregions and vary between healthy subjects, MDD and phobia patients. The determination of the respective interaction and its functional anatomy is essential for developing tDCS to an improved treatment for these pathological conditions. MDD and anticipatory anxiety in specific phobia (spider phobia) are chosen, because MDD has been a focus of the majority of previous clinical tDCS studies and anticipatory anxiety in specific phobia is one of the experimentally best explored conditions within the anxiety disorder spectrum.

 

Research questions


  1. How does anodal tDCS of the DLPFC and the DMPFC modulate resting state and functional fMRI connectivity in healthy subjects? In single experiments, these effects will be additionally elucidated by simultaneous EEG-fMRI measurements.
  2. Is there a difference in the acute effects of PFC tDCS on resting state and functional fMRI connectivity between patients with MDD and healthy subjects?
  3. Is there a difference in the acute effects of PFC tDCS on resting state and functional fMRI connectivity during anticipatory anxiety between patients with specific phobia and healthy subjects?