144 Prefrontal Neurons Modulate Motor Behavior by Targeting Distinct Mediolateral Cortical Sites

Abstract

Abstract INTRODUCTION Injury to the prefrontal cortex (PFC) can result in maladaptive and disinhibited behavior. However, the neural basis for behavioral control of the prefrontal cortex remains largely unknown. Here, we explored the role of the dorsolateral PFC (dlPFC) in orchestrating motor behavior by conducting simultaneous, invasive recordings of the DLPFC, supplementary motor area (SMA), and dorsal premotor (PMd) in primates. METHODS Cortical surface microarrays were implanted into the dlPFC, SMA, and PMd of two monkeys who then participated in a reward-based motor task. For each trial, a monkey received visual instructional cues correlating to a two-step joystick movement plan. They then received cues to either initiate or withhold each step of the plan. Coherence and Granger causality (GC) analysis of the local field potential (LFP) data was used to characterize the interactions between the cortical sites during various behavioral scenarios (initiation, withholding, continuing, or aborting an initiated motor task). RESULTS >Theta band (3-7 Hz) coherence activity was found to most greatly distinguish the four behavioral scenarios. Initiation and continuation cues were associated with increased dlPFC-SMA and dlPFC-PMd coherence (t-test, P < 10e-12), but a more significant increase was seen in dlPFC-SMA compared to dlPFC-PMd (ANOVA, P < 0.001). Inhibition of movement initiation was characterized by dlPFC-SMA coherence increase but lack of dlPFC-PMd coherence change (t-test, P = 0.9). Aborting an already initiated movement sequence was associated with a global decrement in coherence (t-test, P < 10e-35). GC analysis demonstrated that these coherence changes were generally associated with an increase of information flow from the PFC to the more distal mediolateral frontal sites. CONCLUSION We discovered two functional circuitries between the pre-frontal and pre-motor cortices that distinctly control initiation and inhibition of motor behavior. These findings provide an important circuit-based model on which to understand and prospectively treat neuro-cognitive disorders characterized by disinhibition and maladaptation.