Noninvasive Temporal Interference Stimulation: Modulating Associative Memory by Targeting Deep-brain Targets

Summary

Alzheimer's disease and its preclinical stages are characterized by progressive neurodegenerative changes in the hippocampi and default mode network resulting in dysfunctions in episodic memory and its central part the associative memory. Associative memory allows for learning and remembering the relationship between unrelated items. Previous research suggests that non-invasive brain stimulation can influence associative memory but with the caveat of quite a small precision and relatively small effects due to the ability only influence superficial brain areas. Novel Brain stimulation techniques such as temporal interference stimulation (TIS) allow overcoming these caveats by allowing focal non-invasive deep brain stimulation. The main goal of this pilot clinical trial is to modulate associative memory among healthy seniors by influencing the cortico-hippocampal circuits using TIS. Secondly, the goal is to use functional magnetic resonance imaging (fMRI) and EEG to explore the neural correlates of TIS effects on brain networks and find biomarkers that allow predicting better response to brain stimulation.

Conditions

• Healthy Aging
• Memory Disorders in Old Age
• Mild Cognitive Impairment
• Alzheimer Disease

Interventions

COMBINATION_PRODUCT

Non-invasive Temporal Interference stimulation and Face-name association training task targeting the hippocampus

TIS relies on high frequencies which can penetrate with relatively low loss. High-frequency carriers (\>1 kHz) emitted by two (or more) pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency between the carriers. By controlling field orientation and frequency offset, the hot spot of constructive interference can be precisely targeted. The key aspect of this method is the use of carrier waves at frequencies higher than 1 kHz. Frequencies above this range are regarded as non-stimulating and pass-through tissues with relatively low loss. While these higher frequencies do not stimulate neural tissue, the interference envelope of two phase-shifted frequencies can elicit action potentials because the offset (aka "beat") frequency can be tuned accordingly to \< 100 Hz.

COMBINATION_PRODUCT

Non-invasive Temporal Interference stimulation and Face-name association training task targeting the Precuneus

TIS relies on high frequencies which can penetrate with relatively low loss. High-frequency carriers (\>1 kHz) emitted by two (or more) pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency between the carriers. By controlling field orientation and frequency offset, the hot spot of constructive interference can be precisely targeted. The key aspect of this method is the use of carrier waves at frequencies higher than 1 kHz. Frequencies above this range are regarded as non-stimulating and pass-through tissues with relatively low loss. While these higher frequencies do not stimulate neural tissue, the interference envelope of two phase-shifted frequencies can elicit action potentials because the offset (aka "beat") frequency can be tuned accordingly to \< 100 Hz.

COMBINATION_PRODUCT

High-frequency stimulation (placebo) with Face-name association training task

High-frequency (\>1 kHz) stimulation; Standardly used as a carrier frequency; Effects are expected to he high-pass filtered by neurons

Sponsors & Collaborators

• St. Anne's University Hospital Brno, Czech Republic

  collaborator OTHER

• Masaryk University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-01-30

Primary Completion

2025-11-01

Completion

2025-12-12

Countries

• Czechia

Study Locations