Browsing by Author "White, Jason P."

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    Dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange
    Batten, Seth R.; Bang, Dan; Kopell, Brian H.; Davis, Arianna N.; Heflin, Matthew; Fu, Qixiu; Perl, Ofer; Ziafa, Kimia; Hashemi, Alice; Saez, Ignacio; Barbosa, Leonardo S.; Twomey, Thomas; Lohrenz, Terry; White, Jason P.; Dayan, Peter; Charney, Alexander W.; Figee, Martijn; Mayberg, Helen S.; Kishida, Kenneth T.; Gu, Xiaosi; Montague, P. Read (Nature Research, 2024-02-26)
    Dopamine and serotonin are hypothesized to guide social behaviours. In humans, however, we have not yet been able to study neuromodulator dynamics as social interaction unfolds. Here, we obtained subsecond estimates of dopamine and serotonin from human substantia nigra pars reticulata during the ultimatum game. Participants, who were patients with Parkinson’s disease undergoing awake brain surgery, had to accept or reject monetary offers of varying fairness from human and computer players. They rejected more offers in the human than the computer condition, an effect of social context associated with higher overall levels of dopamine but not serotonin. Regardless of the social context, relative changes in dopamine tracked trial-by-trial changes in offer value—akin to reward prediction errors—whereas serotonin tracked the current offer value. These results show that dopamine and serotonin fluctuations in one of the basal ganglia’s main output structures reflect distinct social context and value signals.
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    Noradrenaline tracks emotional modulation of attention in human amygdala
    Bang, Dan; Luo, Yi; Barbosa, Leonardo S.; Batten, Seth R.; Hadj-Amar, Beniamino; Twomey, Thomas; Melville, Natalie; White, Jason P.; Torres, Alexis; Celaya, Xavier; Ramaiah, Priya; McClure, Samuel M.; Brewer, Gene A.; Bina, Robert W.; Lohrenz, Terry; Casas, Brooks; Chiu, Pearl H.; Vannucci, Marina; Kishida, Kenneth T.; Witcher, Mark R.; Montague, P. Read (Elsevier, 2023-11-20)
    The noradrenaline (NA) system is one of the brain’s major neuromodulatory systems; it originates in a small midbrain nucleus, the locus coeruleus (LC), and projects widely throughout the brain. The LC-NA system is believed to regulate arousal and attention and is a pharmacological target in multiple clinical conditions. Yet our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans. Here, we address this problem by showing that electrochemical estimates of sub-second NA dynamics can be obtained using clinical depth electrodes implanted for epilepsy monitoring. We made these recordings in the amygdala, an evolutionarily ancient structure that supports emotional processing, and receives dense LC-NA projections, while patients (n = 3) performed a visual affective oddball task. The task was designed to induce different cognitive states, with the oddball stimuli involving emotionally evocative images, which varied in terms of arousal (low versus high) and valence (negative versus positive). Consistent with theory, the NA estimates tracked the emotional modulation of attention, with a stronger oddball response in a high-arousal state. Parallel estimates of pupil dilation, a common behavioral proxy for LC-NA activity, supported a hypothesis that pupil-NA coupling changes with cognitive state, with the pupil and NA estimates being positively correlated for oddball stimuli in a high-arousal but not a lowarousal state. Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.
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    Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward
    Kishida, Kenneth T.; Sáez, Ignacio; Lohrenz, Terry; Witcher, Mark R.; Tatter, Stephen B.; White, Jason P.; Ellis, Thomas L.; Phillips, Paul E. M.; Montague, P. Read; Laxton, Adrian W. (NAS, 2016-01-05)
    In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson’s disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson’s disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons.