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

Abstract

The dorsal anterior cingulate cortex (dACC) 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 dACC than lPFC, or with a preponderance of dACC projections synapsing onto inhibitory neurons in the lPFC. Here, we tested effective dACC-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 dACC 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 dACC → lPFC resulted, on average, in shorter-latency EFPs than lPFC → dACC. Overall, latencies and connectivity strength varied more than twofold depending on the precise anterior-to-posterior location of the connections. These findings reveal systematic asymmetries in effective connectivity between dACC and lPFC in the awake non-human primate and document the spatial and temporal patchiness of effective synaptic connections. We discuss that our results suggest that measuring effective connectivity profiles will be essential for understanding how asymmetries in local synaptic efficacy and connectivity translate into functional neuronal interactions during adaptive, goal-directed behavior.

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Acknowledgements

This work was supported by a grant from the Canadian Institutes of Health Research (T.W.). CIHR Grant MOP_102482. The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of this manuscript. The authors would like to thank Hongying Wang for technical support.

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Correspondence to Verónica Nácher or Thilo Womelsdorf.

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All animal care and experimental procedures performed in this study have been approved by the local ethics committee, the York University Council on Animal Care, were in accordance with the Canadian Council on Animal Care guidelines, and are in agreement with the 1964 Helsinki Declaration and its later amendments.

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Nácher, V., Hassani, S.A. & Womelsdorf, T. Asymmetric effective connectivity between primate anterior cingulate and lateral prefrontal cortex revealed by electrical microstimulation. Brain Struct Funct 224, 779–793 (2019). https://doi.org/10.1007/s00429-018-1806-y

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Keywords

  • Anterior cingulate cortex
  • Lateral prefrontal cortex
  • Effective connectivity
  • Electrical stimulation
  • Cortical mapping
  • Monkey