Background: Multiple sclerosis (MS) often causes impairment in working memory (WM), information processing speed (IPS), and verbal memory (VM). These deficits are linked to disrupted neural oscillatory activity. Transcranial alternating current stimulation (tACS), which modulates cortical oscillations, may hold promise for treating cognitive impairment in MS.

Objective: To evaluate online and offline effects of gamma (γ)-tACS on WM, IPS, and VM while assessing changes in brain rhythms using electroencephalography (EEG).

Methods: Thirty-six MS patients with single-domain impairment in WM (12), IPS (13), or VM (11) underwent γ-tACS and sham-tACS over the left dorsolateral prefrontal cortex (DLPFC) (WM, IPS) or precuneus (VM). Cognitive performance was assessed pre-tACS (T0), during (T1), and post-tACS (T2) using the Digit Span Backward (DSBW) for WM, Symbol Digit Modalities Test (SDMT) for IPS, and Rey Auditory Verbal Learning Test (RAVLT) for VM. EEG was recorded at T0 and T2 to analyze local power spectral density and local-to-global connectivity.

Results: DSBW, SDMT, and RAVLT scores transiently improved during γ-tACS and not during sham. IPS-impaired patients showed a reduction in spectral power across all frequency bands, at the stimulation site, post-DLPFC γ-tACS.

Conclusions: γ-tACS briefly improves WM, IPS, and VM in MS patients, warranting further trials of this non-invasive intervention.