Reis Carolina, Azizollahi Hamed, Headley Gabriel, Navarro Sergi, Hanslmayr Simon, Clouter Andrew, Zanto Theodore P, Certain Raphael
Clarity Health Technologies, Inc, Wilmington, DE, USA.
Centre for Neurotechnology, School of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.
Sci Rep. 2025 Aug 5;15(1):28491. doi: 10.1038/s41598-025-13725-6.
Alzheimer's disease (AD) presents a critical global health challenge, with current therapies offering limited efficacy and safety in halting disease progression. Gamma sensory stimulation (GSS) has emerged as a promising non-invasive neuromodulation technique that enhances gamma neural synchrony, potentially counteracting AD pathology by promoting glymphatic clearance, reducing neuroinflammation and improving synaptic plasticity. However, existing GSS delivery methods rely on simplistic sensory stimuli that lack user engagement, potentially creating adherence barriers and limiting the full therapeutic potential of this approach. To address this, we investigated whether GSS delivered through virtual reality (VR) could safely and effectively evoke gamma-band neural activity while providing an engaging and tolerable user experience. Sixteen cognitively healthy older adults participated in a single-session, within-subject feasibility study consisting of three VR-based experiments. In each, 40 Hz auditory and/or visual stimuli were presented, and neural responses were recorded using electroencephalography (EEG). Tolerability and safety were assessed via digital questionnaires. Source-level analysis from Experiment 1 confirmed that unimodal auditory and visual stimulation at 40 Hz reliably increased gamma power in their respective sensory cortices. Sensor-level analyses from Experiments 2 and 3 showed that multimodal audiovisual stimulation enhanced both gamma power and inter-trial phase coherence-whether delivered through passive video viewing or integrated into an active cognitive task. Participants reported high comfort and engagement, with no serious adverse events. The findings of this study validate VR as a scalable tool for delivering engaging and cognitively relevant GSS, paving the way for personalized therapies that maximize adherence and therapeutic outcomes. By integrating interactive elements, VR-based GSS may uniquely target memory-related neural networks, offering a novel approach to mitigate neurotoxicity and cognitive decline in AD.
阿尔茨海默病（AD）是一项严峻的全球健康挑战，目前的治疗方法在阻止疾病进展方面疗效和安全性有限。伽马感觉刺激（GSS）已成为一种有前景的非侵入性神经调节技术，可增强伽马神经同步性，可能通过促进类淋巴系统清除、减少神经炎症和改善突触可塑性来对抗AD病理。然而，现有的GSS传递方法依赖于缺乏用户参与度的简单感觉刺激，这可能会造成依从性障碍并限制该方法的全部治疗潜力。为了解决这一问题，我们研究了通过虚拟现实（VR）进行的GSS是否能在提供引人入胜且可耐受的用户体验的同时，安全有效地诱发伽马波段神经活动。16名认知健康的老年人参与了一项单节次、受试者内可行性研究，该研究包括三个基于VR的实验。在每个实验中，呈现40赫兹的听觉和/或视觉刺激，并使用脑电图（EEG）记录神经反应。通过数字问卷评估耐受性和安全性。实验1的源水平分析证实，40赫兹的单峰听觉和视觉刺激可靠地增加了各自感觉皮层中的伽马功率。实验2和3的传感器水平分析表明，多峰视听刺激增强了伽马功率和试验间相位相干性——无论是通过被动视频观看还是整合到主动认知任务中。参与者报告了高度的舒适度和参与度，且无严重不良事件。本研究结果验证了VR作为一种可扩展工具，用于提供引人入胜且与认知相关的GSS，为最大限度提高依从性和治疗效果的个性化治疗铺平了道路。通过整合交互元素，基于VR的GSS可能独特地靶向与记忆相关的神经网络，为减轻AD中的神经毒性和认知衰退提供一种新方法。
