Here, we see a virtual environment (top); the first box shows an orange “landmark,” which is missing in the second box. The third box shows the memorized trajectories to that orange landmark, conveying mental travel. Below, we see the sequential activation of neurons in the prefrontal cortex representing the mental path. Image courtesy of Julio Martinez-Trujillo

Researchers Examine How the Brain Memorizes Complex Information The brain can replay short clips of memorized information, such as our trip to an aisle in a grocery store. This ability—referred to as episodic working memory—is crucial to human behavior, deteriorates early in individuals with dementia, and is affected in individuals with schizophrenia. In a recent study, researchers with the NeuroNex project, The Fabric of the Primate Neocortex and the Origin of Mental Representations, showed that holding complex information in working memory happens through the sequential activation of neurons in the brain’s frontal lobe. As part of the research, the team recorded the activity of neurons in the lateral prefrontal cortex of monkeys as they performed a task that involved remembering and navigating to a location in a virtual 3D environment. The subjects saw a visual cue, remembered its location for a few seconds, and then used a joystick to navigate to that spot for a reward. Using a new mathematical technique developed by NeuroNex researchers Lyle Muller and Alexandra Busch, the team analyzed the recordings and found that neurons were activated in specific sequences that represented locations in the virtual environment held in working memory. These sequences were specific to the complex virtual navigation task, while neuronal activity was organized into more fixed persistent firing patterns in a simpler memory task than the virtual 3D environment. Further, blocking NMDA receptors—specific types of receptors in the brain that help neurons communicate with each other—with low doses of ketamine disrupted both these sequences and working memory performance. These findings show a new way, dependent on NMDA receptors, in which the brain encodes visuospatial working memory in complex environments. They also highlight the flexibility of neural codes in supporting working memory in the lateral prefrontal cortex of primates. “The work reveals a long-searched mechanism for episodic working memory in the brain,” says Julio Martinez-Trujillo, NeuroNex project co-PI and author of the recent paper. The NeuroNex team is also focused on better understanding how neurons in the prefrontal cortex that play memory clips deteriorate prematurely in individuals with Alzheimer’s disease.