Neuroprosthetic Modulation of Large-Scale Brain Networks for Treating Memory Disorders

Introduction

Cognitive deficits caused by ageing, neurodegenerative diseases, or brain injury represent a major public health issue. They are associated with a disruption of neural oscillations in large-scale brain networks, which cannot be restored using current treatments.

Proposed Framework

Here, I propose a new neuromodulation framework for manipulating neural oscillations across large-scale brain networks to improve learning and memory. Specifically, I will create a large-scale neuroprosthesis of the hippocampus-prefrontal cortex circuit, which will simultaneously record and stimulate electrically key areas of the episodic memory network.

Hypothesis

I hypothesize that spatially, spectrally, and temporally specific stimulation protocols within this network will enhance the functional interactions between the hippocampus and prefrontal cortex, and will improve learning and memory. This conceptual approach will be evaluated in non-human primates trained on a visuospatial learning task.

Methodology

1. Device Creation
   First, I will combine an electrocorticographic grid over the prefrontal cortex with depth macroelectrodes in the hippocampus and entorhinal cortex to create a novel large-scale brain implant. I will use this device to investigate the neural signatures of successful vs failed trials.

2. Protocol Optimization
   Next, I will optimize electrical stimulation protocols that replicate successful neural signatures, and will test whether they improve memory in healthy animals.

3. Cognitive Deficit Induction
   Third, I will induce temporary cognitive deficits in the animals using a cholinergic antagonist, and will assess the effects of stimulation in this pharmacological model of dementia.

4. Chronic Feasibility Evaluation
   Finally, I will evaluate the chronic feasibility of this approach by translating these concepts into a fully implantable and wireless platform suited for future clinical applications.

Expected Outcomes

MEMOPROSTHETICS will lead to the development of neuroprostheses that palliate memory deficits in preclinical models of ageing and dementia, and will open new avenues for studying and treating a wide range of cognitive impairments.