Multifield extended high-definition transcranial direct current stimulation in mild cognitive impairment: A proof-of-concept study on cognition and brain network connectivity

BACKGROUND: Treatment of mild cognitive impairment (MCI) could delay the progression of cognitive decline. Noninvasive neuromodulation might restore brain plasticity and lead to clinically meaningful cognitive improvements. OBJECTIVE: To investigate feasibility and tolerability of a multi-field (four regions) extended (80-min-long) intervention using high-definition transcranial direct current stimulation (HD-tDCS) combined with computerized cognitive training (CCT) in participants with MCI and to explore its effects on cognition and brain functional connectivity. METHODS: Double-blinded, randomized proof-of-concept trial of daily sham HD-tDCS + CCT (n = 4) or anodal HD-tDCS + CCT (n = 4) for 15 sessions over 3 months. Four cortical regions were targeted using neuronavigation, including putative frontal coordinates of cognitive reserve and lateral parietal coordinates hypothesized to have robust hippocampal connectivity. Neurocognitive outcomes were assessed at 3 and 6 months and resting-state functional connectivity changes were evaluated at 3 months. Statistical analysis included independent sample t-tests, Wilcoxon rank-sum tests, and Bonferroni correction for multiple comparisons. RESULTS: Eleven subjects were eligible and interviewed, and 8 consented (73% consent rate). All 8 completed the trial with only minor adverse events (100% completion rate). Blinding was successful. A large but non-significant increase in Alzheimer's Disease Cooperative Study-Preclinical Alzheimer's Cognitive Composite scores at 6 months was observed in the anodal group (59.8%) compared with sham (24.5%). Significant declines were seen in left parietal cortex-left caudal hippocampus connectivity (p = 0.004) and right intraparietal sulcus-right frontal eye fields connectivity (p = 0.039) in the anodal group. CONCLUSIONS: The intervention was feasible and well tolerated. Findings suggest possible normalization of aberrant or compensatory hyperconnectivity in MCI. Larger studies are needed.Clinical Trial Number: NCT04246164.