Prefrontal Rhythms for Cognitive Contro

Goal-directed behavior requires flexible selection among action plans and updating behavioral strategies when they fail to achieve desired goals. Lateral prefrontal cortex (LPFC) is implicated in the execution of behavior-guiding rule-based cognitive control while anterior cingulate cortex (ACC) is implicated in monitoring processes and updating rules. Rule-based cognitive control requires selective processing while process monitoring benefits from combinatorial processing. I used a combination of computational and experimental methods to investigate how network oscillations and neuronal heterogeneity contribute to cognitive control through their effects on selective versus combinatorial processing modes in LPFC and ACC.;First, I adapted an existing LPFC model to explore input frequency- and coherence-based output selection mechanisms for flexible routing of rate-coded signals. I show that the oscillatory states of input encoding populations can exhibit a stronger influence over downstream competition than their activity levels. This enables an output driven by a weaker resonant input signal to suppress lower-frequency competing responses to stronger, less resonant (though possibly higher-frequency) input signals. While signals are encoded in population firing rates, output selection and signal routing can be governed independently by the frequency and coherence of oscillatory inputs and their correspondence with output resonant properties. Flexible response selection and gating can be achieved by oscillatory state control mechanisms operating on input encoding populations. These dynamic mechanisms enable experimentally-observed LPFC beta and gamma oscillations to flexibly govern the selection and gating of rate-coded signals for downstream read-out. Furthermore, I demonstrate how differential drives to distinct interneuron populations can switch working memory representations between asynchronous and oscillatory states that support rule-based selection.;Next, I analyzed physiological data from the LeBeau laboratory and built a de novo model constrained by the biological data. Experimental data demonstrated that fast network oscillations at both the beta- and gamma frequency bands could be elicited in vitro in ACC and neurons exhibited a wide range of intrinsic properties. Computational modeling of the ACC network revealed that the frequency of network oscillation generated was dependent upon the time course of inhibition. Principal cell heterogeneity broadened the range of frequencies generated by the model network. In addition, with different frequency inputs to two neuronal assemblies, heterogeneity decreased competition and increased spike coherence between the networks thus conferring a combinatorial advantage to the network.;These findings suggest that oscillating neuronal populations can support either response selection (routing), or combination, depending on the interplay between the kinetics of synaptic inhibition and the degree of heterogeneity of principal cell intrinsic conductances. Such differences may support functional differences between the roles of LPFC and ACC in cognitive control.