# Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study

## TL;DR

This study explores how tDCS affects brain activity in MS patients and healthy individuals, revealing both immediate and cumulative changes in resting-state brain activity.

## Contribution

The study is the first to investigate simultaneous and cumulative effects of tDCS on regional brain activity in MS patients using concurrent tDCS-MRI.

## Key findings

- tDCS induces simultaneous changes in fALFF in cortical and subcortical regions in both MS patients and healthy controls.
- MS patients showed reversed brain activity patterns after repeated tDCS sessions, indicating cumulative effects.
- Long-lasting changes in brain excitation were observed, particularly around the cuneus region in MS patients.

## Abstract

Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following repeated tDCS sessions) on the regional brain activity during rest need further investigation, especially in MS. This study aims to elucidate tDCS’ underpinnings, alongside its therapeutic impact in MS patients, using concurrent tDCS-MRI methods. In total, 20 MS patients (age = 48 ± 12 years; 8 males) and 28 healthy controls (HCs; age = 36 ± 15 years; 12 males) were recruited. They participated in a tDCS-MRI session, during which resting-state functional MRI (rs-fMRI) was used to measure the levels of the fractional amplitude of low-frequency fluctuations (fALFFs), which is an index of regional neuronal activity, before and during left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA for 15 min). MS patients were then asked to return for an identical tDCS-MRI visit (follow-up) after 20 identical at-home tDCS sessions. Simultaneous tDCS-induced changes in fALFF are seen across cortical and subcortical areas in both HC and MS patients, with some regions showing increased and others decreased brain activity. In HCs, fALFF increased in the right pre- and post-central gyrus whilst it decreased in subcortical regions. Conversely, MS patients initially displayed increases in more posterior cortical regions but decreases in the superior and temporal cortical regions. At follow-up, MS patients showed reversed patterns, emphasizing significant cumulative effects of tDCS treatment upon brain excitation. Such long-lasting changes are further supported by greater pre-tDCS fALFFs measured at follow-up compared to baseline, especially around the cuneus. The results were significant after correcting for multiple comparisons (p-FDR < 0.05). Our study shows that tDCS has both simultaneous and cumulative effects on neuronal activity measured with rs-fMRI, especially involving major brain areas distant from the site of stimulation, and it is responsible for fatigue and cognitive and motor skills.