Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review

Abstract

Despite the numerous pharmacological interventions targeting dementia, no disease-modifying therapy is available, and the prognosis remains unfavorable. A promising perspective involves tackling high-frequency gamma-band (> 30 Hz) oscillations involved in hippocampal-mediated memory processes, which are impaired from the early stages of typical Alzheimer’s Disease (AD). Particularly, the positive effects of gamma-band entrainment on mouse models of AD have prompted researchers to translate such findings into humans using transcranial alternating current stimulation (tACS), a methodology that allows the entrainment of endogenous cortical oscillations in a frequency-specific manner. This systematic review examines the state-of-the-art on the use of gamma-tACS in Mild Cognitive Impairment (MCI) and dementia patients to shed light on its feasibility, therapeutic impact, and clinical effectiveness. A systematic search from two databases yielded 499 records resulting in 10 included studies and a total of 273 patients. The results were arranged in single-session and multi-session protocols. Most of the studies demonstrated cognitive improvement following gamma-tACS, and some studies showed promising effects of gamma-tACS on neuropathological markers, suggesting the feasibility of gamma-tACS in these patients anyhow far from the strong evidence available for mouse models. Nonetheless, the small number of studies and their wide variability in terms of aims, parameters, and measures, make it difficult to draw firm conclusions. We discuss results and methodological limitations of the studies, proposing possible solutions and future avenues to improve research on the effects of gamma-tACS on dementia.

Right frontal gamma transcranial alternating current stimulation modulates optimism biases

“…Second, the study's reliance on a single tACS session could limit the detection of enduring or robust stimulation effects. Drawing from previous research (Manippa et al, 2023), multiple sessions of tACS may produce cumulative effects. Therefore, future studies should consider multiple stimulation sessions to capture the potential in uence of HD-tACS on optimistic belief updating.…”

The Bibliometric Analysis of EEGLAB Software in the Web of Science Indexed Articles

“…For example, tDSC and tACS have existed in the niche theme of Figure 4, but they are growing topics in the neuroscience literature. [65,66]. The one direction for future research is bibliographic analysis of special statistical methods with EEGLAB and EEG datasets for example, machine learning methods such as support vector machine [67], dimension reduction methods such as ICA [43] , functional data analysis methods [68,69], and deep learning methods [17,70].…”

A Focused Review of Gamma Neuromodulation as a Therapeutic Target in Alzheimer’s Spectrum Disorders

“…While significantly better established clinically, only two studies utilized TMS, though both demonstrated a positive effect of multiple TMS sessions per week, over 2–6 weeks, targeting DLPFC/parietal areas, or precuneus, on coupling of gamma activity across distributed cortical networks, WM and trail making [ 80 , 83 ]. That TACS, despite being much less well established clinically, exhibits greater popularity than TMS likely arises from TACS being significantly more cost-effective, portable and accessible [ 12 ]. Furthermore, while rare, TMS nevertheless exhibits significantly higher seizure risk than TACS, a potentially serious risk in older patients with neurologic decline [ 85 , 86 ].…”