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

Anodal transcranial direct current stimulation(tDCS) is known to improve cognition in patients with mild cognitive impairment (MCI) and Alzheimers disease(mild AD). 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 & mild AD, n=21) using functional magnetic resonance imaging (fMRI) and magnetoencephalography(MEG). The patients showed significant improvements in episodic memory, learning, and delayed recall following tDCS intervention. 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. 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.