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bioRxiv · 10.1101/2024.04.10.588629

Reward Circuit Local Field Potential Modulations Precede Risk Taking

Hughes, N. C.·Qian, H.·Zargari, M.·Zhao, Z.·Singh, B.·Wang, Z.·Fulton, J. N.·Johnson, G. W.·Li, R.·Dawant, B. M.·Englot, D. J.·Constantinidis, C.·Roberson, S. T. W.·Bick, S. K.
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Abstract

Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking. Eleven patients with pharmacoresistant epilepsy who underwent stereotactic electroencephalography with electrodes in the amygdala, orbitofrontal cortex, insula, and/or anterior cingulate participated. Patients participated in a gambling task where they wagered on a visible playing card being higher than a hidden card, betting $5 or $20 on this outcome, while local field potentials were recorded from implanted electrodes. We used cluster-based permutation testing to identify reward prediction error signals by comparing oscillatory power following unexpected and expected rewards. We also used cluster-based permutation testing to compare power preceding high and low bets in high-risk (<50% chance of winning) trials and two-way ANOVA with bet and risk level to identify signals associated with risky, risk averse, and optimized decisions. We used linear mixed effects models to evaluate the relationship between reward prediction error and risky decision signals across trials, and a linear regression model for associations between risky decision signal power and Barratt Impulsiveness Scale scores for each patient. Reward prediction error signals were identified in the amygdala (p=0.0066), anterior cingulate (p=0.0092), and orbitofrontal cortex (p=6.0E-4, p=4.0E-4). Risky decisions were predicted by increased oscillatory power in high-gamma frequency range during card presentation in the orbitofrontal cortex (p=0.0022), and by increased power following bet cue presentation across the theta-to-beta range in the orbitofrontal cortex (p=0.0022), high-gamma in the anterior cingulate (p=0.0004), and high-gamma in the insula (p=0.0014). Risk averse decisions were predicted by decreased orbitofrontal cortex gamma power (p=2.0E-4). Optimized decisions that maximized earnings were preceded by decreases within the theta to beta range in orbitofrontal cortex (p=2.0E-4), broad frequencies in amygdala (p=2.0E-4), and theta to low-gamma in insula (p=4.0E-4). Insula risky decision power was associated with orbitofrontal cortex high-gamma reward prediction error signal (p=0.0048) and with patient impulsivity (p=0.00478). Our findings identify and help characterize reward circuitry activity predictive of risk-taking in humans. These findings may serve as potential biomarkers to inform the development of novel treatment strategies such as closed loop neuromodulation for disorders of risk taking.

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Hughes, N. C., Qian, H., Zargari, M., Zhao, Z., Singh, B., Wang, Z., Fulton, J. N., Johnson, G. W., Li, R., Dawant, B. M., Englot, D. J., Constantinidis, C., Roberson, S. T. W., Bick, S. K.. 2024-04-11. Reward Circuit Local Field Potential Modulations Precede Risk Taking. https://doi.org/10.1101/2024.04.10.588629

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