Development of non-invasive deep brain stimulation intervention for cognitive decline in Alzheimer’s disease
File(s)
Author(s)
Alania, Ketevan
Type
Thesis
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, for which current treatment options remain limited. Non-invasive brain stimulation (NIBS) has emerged as a promising strategy to modulate aberrant neural activity and associated cognitive symptoms. Temporal Interference (TI) stimulation is a novel technique that addresses key limitations of existing NIBS methods by enabling non-invasive targeting of deep brain structures, with the added potential for concurrent real-time neural monitoring.
This thesis investigates the therapeutic potential of hippocampal TI stimulation for improving episodic memory function in AD. As a first step, the feasibility of single-session hippocampal TI to modulate episodic memory performance was demonstrated in 21 healthy young adults, providing early evidence of both neuromodulatory and behavioural effects. Building on these findings, a 10-day hippocampal TI stimulation protocol was tested in 21 patients with AD to evaluate the safety, tolerability, and feasibility of repeated stimulation. The intervention was well tolerated and resulted in selective improvements in episodic memory. Individual differences in baseline hippocampal volume and task performance during stimulation predicted the degree of memory benefit, suggesting that disease stage may influence responsiveness to TI.
Finally, to address the key methodological challenge of concurrent neural recording during TI stimulation, novel hardware and signal processing strategies were implemented to enable real-time EEG monitoring. These methods allowed reliable detection of steady-state visually evoked potentials during stimulation and revealed frequency- and state-dependent effects of TI on cortical activity.
Collectively, this work demonstrates the feasibility of hippocampal TI stimulation in both healthy individuals and AD patients. It also introduces new methodological tools for real-time neurophysiological monitoring, laying the groundwork for future closed-loop and personalised stimulation paradigms in neurodegenerative disease.
This thesis investigates the therapeutic potential of hippocampal TI stimulation for improving episodic memory function in AD. As a first step, the feasibility of single-session hippocampal TI to modulate episodic memory performance was demonstrated in 21 healthy young adults, providing early evidence of both neuromodulatory and behavioural effects. Building on these findings, a 10-day hippocampal TI stimulation protocol was tested in 21 patients with AD to evaluate the safety, tolerability, and feasibility of repeated stimulation. The intervention was well tolerated and resulted in selective improvements in episodic memory. Individual differences in baseline hippocampal volume and task performance during stimulation predicted the degree of memory benefit, suggesting that disease stage may influence responsiveness to TI.
Finally, to address the key methodological challenge of concurrent neural recording during TI stimulation, novel hardware and signal processing strategies were implemented to enable real-time EEG monitoring. These methods allowed reliable detection of steady-state visually evoked potentials during stimulation and revealed frequency- and state-dependent effects of TI on cortical activity.
Collectively, this work demonstrates the feasibility of hippocampal TI stimulation in both healthy individuals and AD patients. It also introduces new methodological tools for real-time neurophysiological monitoring, laying the groundwork for future closed-loop and personalised stimulation paradigms in neurodegenerative disease.
Version
Open Access
Date Issued
2025-03-29
Date Awarded
2025-10-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Grossman, Nir
Sharp, David James
Sponsor
Alzheimer’s Association
Publisher Department
Department of Brain Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)