Neurophysiological indices of distinct cognitive operations during symbol digit modalities test performance in multiple sclerosis: a pilot study

Objective: The symbol digit modalities test (SDMT) is a clinically relevant and widely used measure of cognitive processing speed and efficiency in people with Multiple Sclerosis (PwMS). The present pilot study identified neurophysiological processes that underly SDMT performance in people with MS (PwMS) compared to healthy controls (HC). Methods: We developed a novel computerized SDMT-event-related potential (cSDMT-ERP) paradigm to obtain neural indices of SDMT performance. Results: PwMS exhibited a redistribution of N2 amplitude, and attenuated P3 amplitude during the cSDMT compared to HCs. Increased amplitude of P1, frontal N2, and parietal-occipital P3 during cSDMT performance were together associated with better standard SDMT performance. Reduced frontal-central N2 amplitude with concomitant enhancement of central P3 amplitude was also associated with better SDMT performance. Finally, more pronounced N1 amplitude was associated with heightened depression symptoms. Conclusions: These analyses indicate that PS disturbances manifest across multiple stages of information processing in PwMS, from early attention (P1 effects), to stimulus conflict monitoring (N2 effects), through stimulus categorization (P3 effects). Significance: The cSDMT-ERP paradigm that we developed (1) has the potential to extend the clinical utility of the SDMT, and (2) provides a theoretical anchoring for the cognitive operations that underly SDMT performance. Further work is needed to validate these preliminary findings.