Understanding mechanisms of learning in prefrontal cortex

Across macaque and man

Among other functions, the prefrontal cortex (PFC) is integral to learning and adapting to uncertain environments. To precisely map PFC neural activity to these cognitive functions, we use a combination of microelectrode recordings in non-human primates (NHPs) and behavioral assessment in patients with obsessive-compulsive disorder (OCD).

When specifically analyzing microelectrode recordings in dorsolateral PFC in NHPs, several neurons were observed to maintain stable information-related spiking activity across cue presentation, motor response, and reward feedback. As this stability varied as a function of learning, we understood this phenomena to underlie credit assignment functionality in the PFC.

Left: Neural recordings across NHPs. Right: Timing of peak cue-related information. From Asaad et al, 2017.

To bridge these experimental findings to the clinic, we work with a unique population of patients with treatment-refractory OCD who undergo surgical ablation of the anterior limb of the internal capsule.

Left: Lesion density across several patients with OCD. Right: Average voxel-wise clinical improvement in the Yale-Brown Obsessive Compsule Scale. From McLaughlin et al, 2021.

In addition to effective relief of OCD symptoms, these lesions (coupled with neuroimaging) provide an opportunity to better understand which structural circuits are involved with OCD pathology. We also investigate whether these same structures produce cognitive functions such as credit assignment and model-based learning by having patients performed structured tasks, including a visual navigation task (“Gridworld”) before and after surgeries.

Left: "Gridworld" task environment, where patients are instructed to navigate to a reward location. Right: As patients progress in the task, "roadblocks" based on their previous performance are used to probe their knowledge of the entire map.

Ongoing work integrates surgery-related changes in learning parameters, clinical improvement, and diffusion-tensor-imaging to better understand the function and pathology present in these fronto-thalamic/striatal circuits.