Non-invasive Neuromodulation of Executive Functions - On the Effects of Transcranial Direct Current Stimulation and Cognitive Control Training

Abstract

Cognitive control (CC) processes allow us to act in a targeted and goal-oriented manner in everyday life. Distracting stimuli, which would otherwise lead to ineffective or even inappropriate actions, are filtered and the behaviour can subsequently be adequately adapted. Deficits in CC, often found in psychiatric disorders such as major depressive disorder (MDD), greatly impair the lives of those affected. Strengthening, improving, or rebuilding CC can be achieved through non-invasive brain stimulation techniques and specialised trainings. These interventions often target the dorsolateral prefrontal cortex (dlPFC), a cortical area that is largely responsible for maintaining CC. However, the effectiveness of these procedures is still highly variable and requires further thorough investigations.

The aim of this work is to investigate to what extent CC processes can be supported by non-invasive interventions in healthy study participants as well as depressed patients. In healthy participants, a structured parameter testing protocol was therefore implemented to determine which transcranial direct current stimulation (tDCS) configuration over the dlPFC improved cognitive processes during performance of a cognitive control training (CCT), the paced auditory serial addition task (PASAT). Additionally, the influence of biological sex on participants' performance was evaluated. Lastly, two different versions of the CCT were tested by patients with MDD to investigate a possible reduction of depressive symptoms, as this task specifically challenges CC functions of the dlPFC.

For the systematic investigation of tDCS parameters, 162 healthy participants underwent a two-week long PASAT training. Each participant received one of nine possible tDCS configurations during the CCT. The configurations were distinguishable by varying polarity, intensity, as well as localisation of the intervention. To investigate the effects of the PASAT in depression, 32 patients were divided into two study groups and received either a pure form of the PASAT or a version enriched with gamification and psychoeducational elements. They then could utilise their assigned training at their own discretion for the duration of six weeks.

Examination of the stimulation parameters revealed that anodal tDCS with an intensity of 1 mA over the left dlPFC resulted in a significant increase in task performance compared to sham stimulation. Other tDCS combinations did not yield superior training effects. Furthermore, when comparing the study groups, this effect was evident in women but not men. These results suggest that there is a beneficial, albeit non-linear, relationship between stimulation intensity and improvement in task performance. Additionally, these performance-increasing effects differ between the sexes. One factor to be emphasised is the large sample size, which allowed to dispel doubts about the effect of tDCS on cognitive functions in general, and the training of CC in particular. The at-home implementation of the PASAT revealed that the version enriched with additional gamification elements led to a lasting significant reduction of patients' depressive symptoms over the pure form of the PASAT, showing the advantage of a specifically adapted CCT for the use in MDD.