Closed-Loop Theta Stimulation in the Orbitofrontal Cortex Prevents Reward-Based Learning.

Neuronal oscillations in the frontal cortex have been hypothesized to play a role in the organization of high-level cognition. Within the orbitofrontal cortex (OFC), there is a prominent oscillation in the theta frequency (4-8 Hz) during reward-guided behavior, but it is unclear whether this oscillation has causal significance. One methodological challenge is that it is difficult to manipulate theta without affecting other neural signals, such as single-neuron firing rates. A potential solution is to use closed-loop control to record theta in real time and use this signal to control the application of electrical microstimulation to the OFC. Using this method, we show that theta oscillations in the OFC are critically important for reward-guided learning and that they are driven by theta oscillations in the hippocampus (HPC). The ability to disrupt OFC computations via spatially localized and temporally precise stimulation could lead to novel treatment strategies for neuropsychiatric disorders involving OFC dysfunction.