Asymmetric effective connectivity between primate anterior cingulate and lateral prefrontal cortex revealed by electrical microstimulation

Abstract

The anterior cingulate cortex (ACC) and lateral prefrontal cortex (lPFC) of the non-human primate show neural firing correlations and synchronize at theta and beta frequencies during the monitoring and shifting of attention. These functional interactions might be based on synaptic connectivity that is equally efficacious in both directions, but it might be that there are systematic asymmetries in connectivity consistent with reports of more effective inhibition within the ACC than lPFC, or with a preponderance of ACC projections synapsing onto inhibitory neurons in the lPFC. Here, we tested effective ACC-lPFC connectivity in awake monkeys and report systematic asymmetries in the temporal patterning and latencies of effective connectivity as measured using electrical microstimulation. We found that ACC stimulation triggered evoked fields (EFPs) were more likely to be multiphasic in the lPFC than in the reverse direction, with a large proportion of connections showing 2-4 inflection points resembling resonance in the 20-30 Hz beta frequency range. Stimulation of ACC → lPFC resulted, on average, in shorter-latency EFPs than lPFC → ACC. Overall, latencies and connectivity strength varied more than two-fold depending on the precise anterior-to-posterior location of the connections. These findings reveal systematic asymmetries in effective connectivity between ACC and lPFC in the awake non-human primate and document the spatial and temporal patchiness of effective synaptic connections. We speculate that measuring effective connectivity profiles will be essential for understanding how local synaptic efficacy and synaptic connectivity translates into functional neuronal interactions to support adaptive behaviors.

Interactions of Medial and Lateral Prefrontal Cortex in Hierarchical Predictive Coding

“…Medial and lateral prefrontal cortex (mPFC/lPFC) are core hubs of the cognitive control and decision-making network in the brain (Cole and Schneider, 2007). The regions are densely and reciprocally connected (Barbas and Pandya, 1989;Barbas and Rempel-Clower, 1997;Nácher et al, 2019), suggesting that their contribution to behavior depends in part on their tightly-coupled interactions during preparation, execution, and monitoring of the consequences of actions. Although these regions have long been the target of focused investigation, it remains an open question as to how they collaborate in an ongoing and interactive fashion to support adaptive behavior (Badre and Nee, 2018).…”