Preliminary Evidence for Perturbation-Based tACS-EEG Biomarkers of Gamma Activity in Alzheimer's Disease

IF 3.6 3区医学 Q2 GERIATRICS & GERONTOLOGY International Journal of Geriatric Psychiatry Pub Date : 2025-01-12 DOI:10.1002/gps.70025

Annalisa Palmisano, Luke R. Pezanko, Davide Cappon, Elisa Tatti, Joanna Macone, Giacomo Koch, Carmelo L. Smeralda, Sara M. Romanella, Giulio Ruffini, Davide Rivolta, Daniel Z. Press, Alvaro Pascual-Leone, Georges El-Fakhri, Emiliano Santarnecchi

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Abstract

Background

Alzheimer's disease (AD) is characterized by impaired inhibitory circuitry and GABAergic dysfunction, which is associated with reduced fast brain oscillations in the gamma band (γ, 30–90 Hz) in several animal models. Investigating such activity in human patients could lead to the identification of novel biomarkers of diagnostic and prognostic value. The current study aimed to test a multimodal “Perturbation-based” transcranial Alternating Current Stimulation-Electroencephalography (tACS)-EEG protocol to detect how responses to tACS in AD patients correlate with patients' clinical phenotype.

Methods

Fourteen participants with mild to moderate dementia due to AD underwent a baseline assessment including cognitive status, peripheral neuroinflammation, and resting-state (rs)EEG. The tACS-EEG recordings included brief (6′) tACS blocks of gamma (i.e., 40 Hz) stimulation administered through 4 different montages, with Pre/Post 32-Channels EEG for each block. Changes in tACS-EEG and rsEEG γ band power with respect to baseline were adopted as a metric of induction and compared with cognitive scores and neuroinflammatory biomarkers.

Results

We found positive correlations between 40 Hz-induced γ activity in fronto-central-parietal areas and patient cognitive status and negative ones with neuroinflammatory markers. Participants with greater cognitive impairment exhibited less γ induction and higher peripheral neuroinflammation. The same analysis performed with spectral power from baseline rsEEG resulted in no significant correlations, promoting the value of tACS-based perturbation for capturing individual differences in pathology-related brain features.

Conclusions

Our work suggests a link between tACS-induced γ band spectral power and clinical severity, with weaker γ induction corresponding to more severe clinical/cognitive impairment. This study provides preliminary support for the development of novel physiological biomarkers and therapeutic targets based on disease severity.

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阿尔茨海默病中基于微扰的tACS-EEG生物标志物的初步证据。

背景：阿尔茨海默病（AD）的特征是抑制回路受损和gaba能功能障碍，在一些动物模型中，这与伽马波段（γ, 30-90 Hz）快速脑振荡减少有关。在人类患者中研究这种活性可能会导致鉴定具有诊断和预后价值的新型生物标志物。目前的研究旨在测试一种多模态“基于微扰”的经颅交流电刺激-脑电图(tACS)-EEG方案，以检测AD患者对tACS的反应如何与患者的临床表型相关。方法：14名因AD引起的轻中度痴呆患者接受了基线评估，包括认知状态、周围神经炎症和静息状态EEG。tACS-EEG记录包括通过4个不同的蒙太奇进行的短（6'）tACS伽马（即40 Hz）刺激，每个区块都有32通道EEG。采用tACS-EEG和rsEEG γ波段功率相对于基线的变化作为诱导指标，并与认知评分和神经炎症生物标志物进行比较。结果：我们发现40hz诱导的额-中央-顶叶区γ活性与患者认知状态呈正相关，与神经炎症标志物呈负相关。认知障碍较大的参与者表现出较少的γ诱导和较高的周围神经炎症。对基线rsEEG的谱功率进行的相同分析没有发现显著的相关性，这促进了基于tac的扰动在捕获病理相关脑特征的个体差异方面的价值。结论：我们的研究表明，tacs诱导的γ波段谱功率与临床严重程度之间存在联系，γ诱导较弱对应的临床/认知障碍越严重。该研究为基于疾病严重程度的新型生理生物标志物和治疗靶点的开发提供了初步支持。

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来源期刊

International Journal of Geriatric Psychiatry 医学-精神病学

CiteScore

6.10

自引率

2.50%

发文量

168

审稿时长

4-8 weeks

期刊介绍： The rapidly increasing world population of aged people has led to a growing need to focus attention on the problems of mental disorder in late life. The aim of the Journal is to communicate the results of original research in the causes, treatment and care of all forms of mental disorder which affect the elderly. The Journal is of interest to psychiatrists, psychologists, social scientists, nurses and others engaged in therapeutic professions, together with general neurobiological researchers. The Journal provides an international perspective on the important issue of geriatric psychiatry, and contributions are published from countries throughout the world. Topics covered include epidemiology of mental disorders in old age, clinical aetiological research, post-mortem pathological and neurochemical studies, treatment trials and evaluation of geriatric psychiatry services.