Information processing speed modulation by electrical brain stimulation in multiple sclerosis: Towards individually-tailored protocols

Information processing speed (IPS) is a core cognitive process, highly relevant in everyday-life and the most frequent and disabling cognitive symptom in patients with Relapsing Multiple Sclerosis (pwRMS). By using region-specific focalized transcranial direct current stimulation (tDCS) in healthy individuals and pwRMS, we provide causal evidence for superior parietal lobe (SPL) involvement in IPS and identified a clinical predictor of tDCS-response in pwRMS. The study employed a registered, randomized, sham-tDCS controlled, three-way blinded, cross-over trial and a mixed-factors design with eight arms [between-subjects: group (pwRMS, controls); tDCS-polarity (excitatory, inhibitory); within-subjects: stimulation (active-, sham-tDCS)]. Concurrently with tDCS, participants completed a computerized version of the Symbol-Digit-Modalities-Test (SDMT), the current gold standard for quantifying IPS impairment in pwRMS. Bayesian modeling with generalized linear mixed models provided strong evidence for polarity specific modulation of IPS by SPL-tDCS and a double-dissociation of stimulation response in pwRMS and controls. Healthy individuals showed the canonical pattern of significantly enhanced and reduced processing speed during excitatory or inhibitory tDCS. In pwRMS, a reversed pattern was found and tDCS-response was predicted by baseline SDMT performance; i.e., more or less impaired patients benefited from inhibitory or excitatory tDCS, respectively. Our results provide direct causal evidence for SPL involvement in IPS in health and disease and suggest that the degree of IPS impairment in pwRMS reflects compensatory or dysfunctional neuroplastic processes that can be counteracted in a polarity specific way. Identified standardized transition scores for the effectiveness of excitatory or inhibitory tDCS will inform future individually-tailored stimulation protocols in pwRMS.