Disorder-tailored Transcranial Direct Current Stimulation (tDCS) of the Prefrontal Cortex

Major depressive disorder (MDD) is a common, recurrent, and frequent chronic disorder. Among others, deficient cognitive control over emotional distraction is a central characteristic of MDD (Ochsner \& Gross 2005; Disner et al. 2011; Beck 2008). Hypoactivation of the dorsolateral prefrontal cortex (DLPFC) has been linked with this deficit (Dolcos \& McCarthy 2006). Moreover, aberrant functional connectivity patterns have been found in MDD patients (Kaiser et al. 2015). Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that has been largely investigated in experimental neurosciences and tDCS of the prefrontal cortex (PFC) has been proposed as novel treatment in MDD. In addition, it is increasingly investigated as treatment for negative symptoms in schizophrenia (SCZ) (Brunelin et al. 2012). So far, prefrontal tDCS has been shown to enhance cognitive control over emotional distraction in MDD patients (Wokenstein \& Plewnia 2013). Also, tDCS-induced connectivity changes found in fMRI studies comparing resting-state networks configurations before and after prefrontal tDCS may reflect a state of enhanced alertness (Keeser, Meindl, et al., 2011; Park et al., 2013). The aim of this study is to investigate the neurophysiological correlates of tDCS effects in patients with different psychiatric disorders for which tDCS is a possible intervention, in particular MDD and SCZ, as compared to healthy individuals. For this purpose, we determine the most promising protocol in from investigations in healthy volunteers and apply this protocol in the patient sample including age- and gender-matched controls. First, functional magnetic resonance imaging (fMRI) data is collected during the execution of a cognitive control task as well as during a resting-state condition together with application of real or sham tDCS inside the scanner. It is hypothesized that prefrontal tDCS as compared to sham a) reduces distractibility by compensating for deficient DLPFC activity and b) enhances functional connectivity in networks associated with externally directed attention or cognitive engagement. Second, magnetic resonance spectroscopy (MRS) is performed to measure concentrations of GABA and glutamate in target regions of tDCS. It is hypothesized that tDCS effects are mediated via modulation of the inhibitory/excitatory systems and GABA and glutamate are used as markers of these systems. In this placebo-controlled study healthy volunteers and patients with a diagnosis of MDD or SCZ receive a single treatment with prefrontal tDCS (anode over electrode position F3, cathode over F4, 20 min, 2mA intensity) or sham tDCS (frequency and duration correspondent active tDCS, ramp in and ramp out periods only without intermittent stimulation). We conduct resting-state and MRS measurements combined with application of tDCS in the fMRI scanner. Subsequently, participants perform the cognitive control task (in dependence of Plewnia, C., Schroeder, P. A., \& Wolkenstein, L. (2015)) in the scanner. The participants are assigned to either the real or sham tDCS condition according to a randomised, double-blind parallel design.