A functional MRI and magnetoencephalography study of the cognitive modulatory effect of transcranial direct current stimulation in early Alzheimer’s disease

Objective Anodal transcranial direct current stimulation (tDCS) is known to improve cognition in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (mild AD). Methods We aimed to examine the brain functional alterations accompanying improvement in cognitive performance following anodal tDCS at the left dorsolateral prefrontal cortex (DLPFC) in a sample of patients with early AD ( N = 40; MCI, n = 19, and mild AD, n = 21) using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). Results Significant (p-FDR < 0.05) reduction in seed(left middle frontal gyrus, lMFG)-to-voxel resting-state functional connectivity (rsFC) with precuneus and posterior cingulate gyrus (PCC) was noted following tDCS intervention, while task-based fMRI (tbfMRI) analysis revealed significant (p-FDR < 0.05) increases in blood oxygen level-dependent (BOLD) activations at PCC and right MFG (rMFG) during episodic memory encoding and retrieval tasks, respectively. Furthermore, a significant decrease (p-FDR < 0.05) in resting-state MEG (rsMEG) gamma power at the right occipital cortex and an increase in phase (theta) and amplitude (gamma) coupling at the left entorhinal cortex were observed post-tDCS. Conclusion The findings of this comprehensive study using resting fMRI and MEG, as well as task-based fMRI, provide mechanistic insights regarding brain functional alterations that underlie the cognitive modulatory effects of anodal tDCS in early AD.