Multi-channel transcranial direct current stimulation (mc-tDCS): a novel approach to modulate smooth pursuit eye movement control in healthy individuals and patients with psychotic disorders (DFG Schizo)

Basic data for this project

Description

The neural networks subserving smooth pursuit eye movements provide an ideal model for investigating sensorimotor interaction during ongoing movements. In psychotic disorders, smooth pursuit deficits represent one of the oldest neurophysiological biomarkers. Despite intense research using behavioral and functional magnetic resonance imaging (fMRI) the nature of these deficits and their relation to disease mechanisms of psychosis are unresolved. Specifically, it is still unclear to what extent impaired visual motion information processing in occipito-temporo-parietal networks, i.e. visual area V5, and disturbances in prefrontal areas, i.e. frontal eye fields (FEF), represent causes of pursuit deficits in patients. Alternatively, patients may rely strongly on prefrontal input (FEF) to compensate for visual motion processing deficits (V5), a hypothesis derived from own previous studies. Given this ambiguity, the major aim of this study is to determine the specific functional contributions of V5 and FEF to smooth pursuit control in psychosis patients. We will develop novel individually-optimized multi-channel transcranial direct current stimulation (mc-tDCS) protocols to specifically manipulate neural activity in V5 and FEF. Our mc-tDCS approach will include novel finite element method (FEM) based current flow optimization for computing individualized stimulation currents based on calibrated realistic head models that achieve highest intensity and directionality in V5 and FEF. Individual targeting for mc-tDCS and head model calibration will incorporate multimodal information from FEM-based combined electro- (EEG) and magnetoencephalography (MEG) source analysis and structural MRI and fMRI data to reconstruct V5 and FEF in each participant individually. A highly important aspect is to evaluate the efficacy and efficiency of our novel approach compared to standard bipolar tDCS. We hypothesize that inhibitory individual mc-tDCS of V5 and FEF in healthy participants will mimic smooth pursuit impairments as typically observed in patients. These only temporary impairments include a disturbance of smooth pursuit initiation due to disturbed motion processing in V5 and a pursuit maintenance deficit elicited by disturbed generation of the oculomotor command in FEF. Accordingly, excitatory mc-tDCS of V5 and FEF in patients should attenuate these deficits. Furthermore, excitatory mc-tDCS of FEF will increase otherwise slow eye velocity during smooth pursuit of invisible targets in both healthy participants and patients by supporting the recruitment of extraretinal predictive mechanisms.Our results will provide a functional model not only for alterations but also for relevant compensatory mechanisms in neural networks for sensorimotor processing and motor control. This should pave the way for novel approaches using mc-tDCS to modulate and improve sensory integration impairments associated with psychosis, and potentially other neuropsychiatric disorders.