To investigate the feasibility of a novel multi-field (four regions), extended (80-minute sessions) approach to HD-tDCS combined with Computerized Cognitive Training (CCT); to begin exploring its effects on cognition and on brain functional connectivity, including cortical-hippocampal changes. 

Early treatment of MCI could delay cognitive decline. With customized protocols noninvasive neuromodulation could help restore the brain’s plastic properties while a higher total dose delivered might translate into larger behavioral gains. Moreover, stimulation of the dominant lateral parietal cortex has been shown to modulate cortical-hippocampal networks and enhance associative memory in healthy young and older adults.  

Double-blinded, randomized trial of daily sham HD-tDCS + CCT (n=4) or anodal HD-tDCS + CCT (n = 4) for 15 sessions over 3 months. We targeted four cortical regions using neuronavigation: putative frontal coordinates of cognitive reserve, and lateral parietal coordinates with a hypothesized robust connection to the hippocampus. Neurocognitive outcomes were assessed at 3 and 6 months and resting connectivity changes at 3 months. Analysis used Wilcoxon-rank sum tests and Bonferroni correction for multiple comparisons. 

All completed the trial with minor side effects. Blinding was successful. We found a larger increase in ADCS-PACC at 6 months for Anodal (65%) compared to Sham (14%), but not statistically significant.  The anodal treatment was associated with a lowering of depression and anxiety (p=0.018). Importantly, the Anodal group trended towards higher depression (p=0.059) and Anxiety (p=0.078) at baseline. Anodal stimulation was associated with a decline in left Parietal Cortex-left Caudal Hippocampus connectivity compared to Sham (p=0.042). 

The intervention was well tolerated.  Results should be interpreted   with caution given the small sample size.  Modulation of the left cortical-hippocampal network replicates prior key results in healthy populations. Findings might represent a normalization of an aberrant and/or compensatory hyperconnectivity previously described in MCI. Larger studies are needed to further elucidate these findings.