Novel Individualized Brain Stimulation, Network-based Approaches to Improve Cognition in Healthy Seniors and Patients With MCI
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 3
- 主要终点
- Working memory performance
研究概览
简要总结
Working memory (WM) relies on a vast network comprising cortical and subcortical structures and its impairment is frequent in normal aging, mild cognitive impairment (MCI) and dementia, often driving fucntional decline. Recent studies have shown that non-invasive brain stimulation (NIBS) methods can modulate neuronal activity, and brain network interactions. A significant body of literature has shown that both striatum and cerebellum are reciprocally connected and implicated in WM performance. However, to date, NIBS studies have mainly focused on cerebellar stimulation with transcranial magnetic stimulation (TMS), often yielding inconclusive or conflicting results. In the investigator hypothesis, sequential and concurrent stimulation of multiple brain regions of the WM subcortical network (i.e. targeting striatum and cerebellum) via transcranial temporal interference stimulation (tTIS) and/or repetitive transcranial magnetic stimulation (rTMS) could enhance WM performance in healthy elderly and/or MCI patients. Moreover, combining different stimulation techniques with multimodal neuroimaging and computational modeling, the investigators expect to acquire better mechanistic understanding through which different NIBS act on the brain and improves cognitive functions.
详细描述
Executive functions and particularly working memory (WM) play a crucial role in daily life and is frequently impaired in patients with mild cognitive impairment (MCI), constituting one of the driving factors that compromise quality of life and autonomy. WM specifically relies on a vast brain network of cortical and subcortical regions. Among the different subcortical structures implicated in executive functions, both striatum and cerebellum have been linked to WM performance with complementary roles. Striatum is variably affected in the course of different neurodegenerative diseases, while in contrast, the cerebellum has been associated with cognitive resilience and brain reserve, making it a promising target for interventions for cognitive enhancement.
Hence, leveraging the reciprocal striato-cerebellar connections, in this multi-center, randomized, placebo-controlled proof-of-concept trial, the investigators implemented a sequential multifocal plasticity-inducing stimulation of the striatum and the cerebellum to enhance WM in MCI patients.
The investigators will apply an excitatory intermittent theta burst (iTBS) cerebellar TMS to target the left inferior cerebellar hemisphere and transcranial temporal interference stimulation (tTIS) with the same pattern to focally neuromodulate the striatum in MCI patients. In our hypothesis, this combined sequential protocol will synergistically enhance WM performance.
The investigators will analyse not only the resulting behavioral data as the main outcome, but via multimodal neuroimaging (structural and functional magnetic resonance imaging; s/fMRI) and computational modeling methods they will dissect the network mechanisms and patterns of intrinsic connectivity changes underlying the behavioral changes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age > 18 years old;
- •Clinical diagnosis of MCI due to possible or probable Lewy Bodies Dementia or amnestic MCI following core clinical and neuropsychological criteria.
- •For Healthy Elderlies:
- •Age > 60 years old;
- •Normal performance on baseline cognitive screening.
排除标准
- •presence of dementia as assessed by a cognitive test battery and evaluation of daily activities, any major psychiatric disorder (including major depressive episode);
- •history of another neurological disease affecting central nervous system (e.g., tumor, epilepsy, stroke, etc.);
- •severe or repeated head injury;
- •non-compensated systemic or oncological disease;
- •presence of MRI-incompatible metal in the body (e.g., cardiac pacemaker).
结局指标
主要结局
Working memory performance
时间窗: through study completion, an average of 1 year
The investigators will compare the baseline-normalized reaction time (in milliseconds) and error rate (number of correct and incorrect responses) of a visual working memory task between the active tTIS and tTIS and TMS and the placebo stimulation condition in a cross-over design.
Working memory performance
时间窗: through study completion, an average of 1 year
The investigators will compare the baseline-normalized reaction time (in milliseconds) and error rate (number of correct and incorrect responses) of a visual working memory task between the active tTIS and tTIS and TMS and the placebo stimulation condition in a cross-over design.
次要结局
- The neural underpinnings of NIBS-induced changes quantified by s/fMRI and network-based analytical approaches.(The changes will be computed from the difference between connectivity at baseline and 1 hour post-stimulation.)
研究者
Friedhelm Hummel
Professor
Ecole Polytechnique Fédérale de Lausanne