Anodal HD-tDCS on the dominant anterior temporal lobe and dorsolateral prefrontal cortex: clinical results in patients with mild cognitive impairment.

OBJECTIVES: Mild cognitive impairment (MCI) is a neurocognitive disorder in which the cognitive and mental abilities of humans are declined. Transcranial direct-current stimulation (tDCS) is an emerging noninvasive brain stimulation technique aimed at neuromodulation. In this study, we investigate whether high-definition anodal tDCS stimulation (anodal HD-tDCS) in MCI patients in two different brain regions will be effective in improving cognitive function. METHODS: This study was done as a randomized, double-blind clinical trial. Sixty MCI patients (clinically diagnosed by expert neurologists) were randomly divided into three groups. Two groups received 2-mA anodal HD-tDCS for 20 min for 2 weeks (5 consecutive days in each week, 10 days in total). In the first group (twenty patients), the left dorsolateral prefrontal cortex (left DLPFC) was targeted. In the second group (twenty patients), the target zone was the dominant anterior temporal lobe (DATL). The third group (twenty patients) formed the Sham group. The Montreal Cognitive Assessment (MoCA) and Quality of Life in Alzheimer's Disease (QoLAD) were considered as the outcome measures. RESULTS: MCI patients obtained the highest MoCA mean scores in both left DLPFC and DATL groups versus the study baseline 2 weeks after the intervention. In addition, the MoCA mean scores of MCI patients were greater in both intervention groups compared to the Sham group up to 3 months post-stimulation (p-value ≤ 0.05). However, as we moved away from the first stimulation day, a decreasing trend in the MoCA mean scores was observed. Moreover, in the left DLPFC and DATL groups, higher QoLAD mean scores were observed 3-month post-stimulation, highlighting the effectiveness of anodal HD-tDCS in improving the quality of life in MCI patients. CONCLUSION: In this research, it was shown that applying anodal HD-tDCS at left DLPFC and DATL brain regains for two successive weeks improves cognitive function in MCI patients (by obtaining higher values of MoCA scores) up to 3 months after the intervention compared to the Sham group. This illustrates the positive effects of HD-tDCS, as a non-pharmacological intervention, for improving cognitive function and quality of life in MCI patients. SIGNIFICANCE: Two weeks after anodal HD-tDCS of the DLPFC and DATL brain regions, the MCI patients achieved the highest MoCA mean scores compared to the Sham group across all measurement intervals.

The impact of selective and non-selective medial septum stimulation on hippocampal neuronal oscillations: A study based on modeling and experiments.

Alzheimer's disease (AD) is a neurodegenerative disorder with a rising socioeconomic impact on societies. The hippocampus (HPC), which plays an important role in AD, is affected in the early stages. The medial septum (MS) in the forebrain provides major cholinergic input to the HPC and has been shown to play a significant role in generating oscillations in hippocampal neurons. Cholinergic neurons in the basal forebrain are particularly vulnerable to neurodegeneration in AD. To better understand the role of MS neurons including the cholinergic, glutamatergic, and GABAergic subpopulations in generating the well-known brain rhythms in HPC including delta, theta, slow gamma, and fast gamma oscillations, we designed a detailed computational model of the septohippocampal pathway. We validated the results of our model, using electrophysiological recordings in HPC with and without stimulation of the cholinergic neurons in MS using designer receptors exclusively activated by designer drugs (DREADDs) in healthy male ChAT-cre rats. Then, we eliminated 75% of the MS cholinergic neurons in the model to simulate degeneration in AD. A series of selective and non-selective stimulations of the remaining MS neurons were performed to understand the dynamics of oscillation regulation in the HPC during the degenerated state. In this way, appropriate stimulation strategies able to normalize the aberrant oscillations are proposed. We found that selectively stimulating the remaining healthy cholinergic neurons was sufficient for network recovery and compare this to stimulating other subpopulations and a non-selective stimulation of all MS neurons. Our data provide valuable information for the development of new therapeutic strategies in AD and a tool to test and predict the outcome of potential theranostic manipulations.