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Common medial frontal mechanisms of adaptive control in humans and rodents

Abstract

In this report we describe how common brain networks within the medial frontal cortex (MFC) facilitate adaptive behavioral control in rodents and humans. We demonstrate that after errors, low-frequency oscillations below 12 Hz are modulated over the midfrontal cortex in humans and within the prelimbic and anterior cingulate regions of the MFC in rats. These oscillations were phase locked between the MFC and motor areas in both rats and humans. In rats, single neurons that encoded prior behavioral outcomes were phase coherent with low-frequency field oscillations, particularly after errors. Inactivating the medial frontal regions in rats led to impaired behavioral adjustments after errors, eliminated the differential expression of low-frequency oscillations after errors and increased low-frequency spike-field coupling within the motor cortex. Our results describe a new mechanism for behavioral adaptation through low-frequency oscillations and elucidate how medial frontal networks synchronize brain activity to guide performance.

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Figure 1: Common mechanisms of medial frontal cortical oscillations during adaptive control in rats and humans.
Figure 2: Time-frequency analysis revealing enhanced low-frequency power after errors.
Figure 3: Medial frontal single neuron spiking is coupled with low-frequency oscillations.
Figure 4: Encoding of previous outcomes in the medial frontal and motor cortices.
Figure 5: Loss of adaptive control after inactivation of the MFC.
Figure 6: Inactivation of the MFC eliminated post-error increases in low-frequency oscillations in the motor cortex.
Figure 7: The rat MFC directly influences post-error low-frequency oscillations in the motor cortex in the service of adaptive control.

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Acknowledgements

We thank S. Masters for help with human data acquisition, N. Horst for technical editing and G.R. Yang for help with spike-field coherence code and simulations. This work was funded by National Institute of Neurological Disorders and Stroke grant K08 NS078100 to N.S.N., US National Institutes of Health (NIH) grant MH080066-01 and National Science Foundation (NSF) grant 1125788 to M.J.F., and NIH grant P01-AG030004-01A1 and NSF grant 1121147 to M.L.

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Authors

Contributions

N.S.N., J.F.C., M.J.F. and M.L. designed experiments and wrote the paper. N.S.N. and J.F.C. conducted experiments. N.S.N., J.F.C. and M.L. analyzed data.

Corresponding author

Correspondence to Mark Laubach.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Recording sites in the rat medial frontal cortex.

Supplementary Figure 2 Human phase coherence between mid-frontal (electrode Cz) and target sites.

a) As demonstrated in the main text, there was a significant increase in theta-band phase coherence between mid-frontal (Cz) and motor (C4) sites during the motor action to initiate the trial after errors vs. correct responses (mean phase locking value=.08). b) This enhancement in phase consistency with mid-frontal areas was not observed with an intermediate electrode (C2), and in fact the directionality was reversed (magenta area: mean phase locking value=-.02). This pattern demonstrates that the mid-frontal – motor coherence observed in (a) is not due to volume conduction, as the intermediary site would be enhanced in that case.

Supplementary Figure 3 Amplitudes of medial frontal low-frequency oscillations (LFO) were larger prior to post-error trials compared to post-correct trials.

The left plot shows the average amplitude of local field potentials (below 12 Hz) for the 3-sec period before the trials for data from 6 rats. The right plot shows the ratios of amplitude on post-error and post-correct trials. Amplitudes were significantly larger on post-error trials (paired t-test: t=-4.23, df=5, p<0.01). Ratios for local fields from all 6 rats were larger than 1. The mean ratio is depicted by the + symbol.

Supplementary Figure 4 Spectral analysis of motor cortical field potentials.

Whereas Figure 7 showed spike-field coupling, here we detail power. There was elevated power between 1 and 12 Hz on post-error trials in a) control sessions and b) with medial frontal cortex inactivated. Power was more similar between post-error and post-correct trials when medial frontal cortex was inactivated. c) Direct comparison of differential post-error vs. post-correct trials on control sessions vs sessions with medial frontal cortex inactivated. Differential power between post-correct and post-error trials diminished in medial frontal inactivation sessions. Black contours indicate significant differences via a t-test between control and medial frontal inactivation sessions (p<0.05).

Supplementary Figure 5 Direct comparison of differentials in spike-field coherence on post-error vs. post-correct trials in control sessions vs. sessions with medial frontal cortex inactivated.

Black contours indicate significant differences via a t-test between control and medial frontal inactivation sessions (p<0.05).

Supplementary Figure 6 Summary of findings.

a) After errors, low frequency oscillations in medial frontal cortex are characterized by: 1) increased power, 2) enhanced influence over slowing of responses, 3) robust spike-field coherence of neurons which contain information about the need for control, and 4) phase consistency with low frequency oscillations in motor cortex that influences adjustments in response latency. b) When medial frontal cortex is inactivated, adaptive post-error slowing of responses is specifically diminished, low frequency oscillations are no longer specific to post-error trials and spike-field coupling is changed. However, spikes in motor cortex continue to predict response latency. These findings reveal mechanisms how the medial frontal cortex influences and regulates motor cortex in service of adaptive control.

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Narayanan, N., Cavanagh, J., Frank, M. et al. Common medial frontal mechanisms of adaptive control in humans and rodents. Nat Neurosci 16, 1888–1895 (2013). https://doi.org/10.1038/nn.3549

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