Abstracts

Rationale: In the Morris water-maze (MWM) task, rodents are trained to find a submerged platform in a pool of opaque water using the configuration of external cues present in the room. This task is widely used to assess spatial memory performance as a surrogate for episodic memory capabilities. The performance of rat models of temporal lobe epilepsy (TLE) is dramatically impaired in the MWM task, a finding that parallels the memory impairments observed in patients with TLE. Here, we developed a virtual reality analogue to the MWM task and asked whether TLE patients were impaired in the task, as observed in rodents. In parallel we tested whether intra-hippocampal local field potentials could be recorded as patients performed the task. Methods: The Human MWM task was developed using the "Source Engine" (Valve™). The virtual WM was presented on a laptop computer and a gamepad controller was provided. Eleven healthy volunteers and six patients with epilepsy participated in the study. The human WM environment consisted of a rectangular room (10240x10240 pixels, h=512 pixels; 1 ft=16 pixels) with a cylindrical arena (2r=1024 pixels, h=64 pixels) at the center with opaque water (h=12 pixels), surrounded by multiple visual cues. A platform (64x64 pixels, h=12 pixels) was submerged r/3 away from the edge. After habituation to the control scheme, subjects were dropped in the arena and asked to reach the platform as quickly as possible. Survival analysis was performed to assess performance. Electrophysiological recordings were made in the patients with epilepsy to assess oscillatory and single-unit activity during the task. Results: The Human MWM task was developed using the "Source Engine" (Valve™). This software is widely used to create custom video-game environments. The virtual WM was presented on a laptop computer and a gamepad controller was provided. Movements were restricted to forward/back and left/right panning. Eleven healthy volunteers and six patients with epilepsy participated in the study. The human WM environment consisted of a rectangular room (10240x10240 pixels, h=512 pixels; 1 ft=16 pixels) with a cylindrical arena (2r=1024 pixels, h=64 pixels) at the center with opaque water (h=12 pixels), surrounded by multiple visual cues. A platform (64x64 pixels, h=12 pixels) was submerged r/3 away from the edge. After habituation to the control scheme, subjects were dropped in the arena and asked to reach the platform as quickly as possible. This process was repeated 4 times per session for 3 sessions with a minute of rest in between followed by a probe trial. Survival analysis was performed to assess performance. Electrophysiological recordings were made in the patients with epilepsy to assess oscillatory and single-unit activity during the task. Conclusions: These preliminary results show a deficit in the MWM task in patients with epilepsy and present a striking parallel to previous rodent data. The task is easy to learn and performance improved within a few trials. The virtual MWM holds great promise as a translational research tool.