DEEP BRAIN STIMULATION OF THE HIPPOCAMPAL FORMATION DURING A VISUOSPATIAL ASSOCIATIVE MEMORY TASK IN NON-HUMAN PRIMATES

Coupled theta (4-8Hz) and gamma (30-80Hz) oscillations between prefrontal cortex (PFC), entorhinal cortex (EC) and hippocampus (HC) are crucial for associative memory processes. These oscillations are disrupted in memory disorders such as Alzheimer’s disease. Small proof-of-concept studies in epileptic patients have attempted to modulate memory encoding and retrieval using intracranial electrical stimulation of limbic or neocortical structures, yielding conflicting results. Here, we first sought to investigate the neurophysiological bases of associative memory processes in non-human primates chronically implanted with intracranial electrodes spanning the HC, EC, and PFC. Next, we tested the hypothesis that electrical stimulation of these structures would affect memory performance.
To this end, we integrated advanced multi-camera neuronavigation, high-resolution multimodal neuroimaging, and tailored surgical procedures to chronically implant electrodes in deep structures, with an accuracy below or at the millimeter scale. We then combined the implantation of stereo-EEG probes with an ECoG grid on the prefrontal cortex. We leveraged these technologies to conduct chronic electrophysiological recordings during an episodic memory task in two non-human primates. These recordings revealed modulation of intracranial EEG activity during correct and incorrect trials. Finally, we applied electrical stimulation to the hippocampus and entorhinal cortex during the encoding phase (50 Hz continuous and 5 Hz burst stimulation). We found that electrical stimulation systematically impaired memory performance when stimulation was applied above a certain threshold, challenging earlier positive effects observed in epileptic patients.
Future work will investigate the neural states associated with correct and incorrect trials, and how they are affected by electrical stimulation.