Browsing by Author "Kishida, Kenneth T."

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    A computational approach to “free will” constrained by the games we play
    Kishida, Kenneth T. (Frontiers, 2012-09-27)
    Human choice is not free—we are bounded by a multitude of biological constraints. Yet, within the various landscapes we face, we do express choice, preference, and varying degrees of so-called willful behavior. Moreover, it appears that the capacity for choice in humans is variable. Empirical studies aimed at investigating the experience of “free will” will benefit from theoretical disciplines that constrain the language used to frame the relevant issues. The combination of game theory and computational reinforcement learning theory with empirical methods is already beginning to provide valuable insight into the biological variables underlying capacity for choice in humans and how things may go awry in individuals with brain disorders. These disciplines operate within abstract quantitative landscapes, but have successfully been applied to investigate strategic and adaptive human choice guided by formal notions of optimal behavior. Psychiatric illness is an extreme, but interesting arena for studying human capacity for choice. The experiences and behaviors of patients suggest these individuals fundamentally suffer from a diminished capacity of willful choice. Herein, I will briefly discuss recent applications of computationally guided approaches to human choice behavior and the underlying neurobiology. These approaches can be integrated into empirical investigation at multiple temporal scales of analysis including the growing body of experiments in human functional magnetic resonance imaging (fMRI), and newly emerging sub-second electrochemical and electrophysiological measurements in the human brain. These cross-disciplinary approaches hold promise for revealing the underlying neurobiological mechanisms for the variety of choice capacity in humans.
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    Defensive Neurophysiological Response: Exploring the Neural and Autonoic Correlates of Social Behavior
    Patriquin, Michelle Anne (Virginia Tech, 2013-04-01)
    Current literature suggests neurological (i.e., insula, amygdala) and autonomic (i.e., respiratory sinus arrhythmia; RSA) markers of language, social, and behavioral challenges in autism spectrum disorders (ASD; Bal et al., 2010; DiMartino, Ross, et al., 2009; Lorenzi, Patriquin, & Scarpa, 2011; Patriquin, Scarpa, Friedman, & Porges, 2011), that hypothetically reflect a defensive neurophysiological circuit (i.e., hyper-arousal within the central and autonomic nervous systems). It is unknown how this neurophysiological state contributes to difficulties in ASD. Therefore, the current study quantified peripheral and central nervous system activity and investigated how this neurophysiological circuit may be related to different social and behavioral patterns that characterize ASD. Participants with (n = 16) and without (n = 30) ASD listened to classical music while brain (via functional magnetic resonance imaging) and autonomic (via pulse oximeter and plethysmogram) data were collected. Results indicated that decreased insula and amygdala activity during physiological hyper-aroused states predicted symptoms associated with ASD, and predicted higher levels of comorbid anxiety, stress, and depression. Contrary to hypotheses, no baseline RSA or amygdala differences were noted between ASD and controls groups, suggesting that adults with ASD may have developed effective coping strategies for reducing physiological threat responses. It will be important for future studies to continue to explore and clarify the neural connections of peripheral nervous system activation in individuals with and without ASD, including extending this research to children.
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    Diminished single-stimulus response in vmPFC to favorite people in children diagnosed with Autism Spectrum Disorder
    Kishida, Kenneth T.; De Asis-Cruz, Josepheen; Treadwell-Deering, Diane; Liebenow, Brittany; Beauchamp, Michael S.; Montague, P. Read (2019-07)
    From an early age, individuals with autism spectrum disorder (ASD) spend less time engaged in social interaction compared to typically developing peers (TD). One reason behind this behavior may be that the brains of children diagnosed with ASD do not attribute enough value to potential social exchanges as compared to the brains of typically developing children; thus, potential social exchanges are avoided because other environmental stimuli are more highly valued by default. Neurobiological investigations into the mechanisms underlying value-based decision-making has shown that the ventral medial prefrontal cortex (vmPFC) is critical for encoding the expected outcome value of different actions corresponding to distinct environmental cues. Here, we tested the hypothesis that the responsiveness of the vmPFC in children diagnosed with ASD (compared to TD controls) is diminished for visual cues that represent highly valued social interaction. Using a passive picture viewing task and functional magnetic resonance imaging (fMRI) we measured the response of an a priori defined region of interest in the vmPFC in children diagnosed with ASD and an age-matched TD cohort. We show that the average response of the vmPFC is significantly diminished in the ASD group. Further, we demonstrate that a single-stimulus and less than 30 s of fMRI data are sufficient to differentiate the ASD and TD cohorts. These findings are consistent with the hypothesis that the brains of children with ASD do not encode the value of social exchange in the same manner as TD children. The latter finding suggests the possibility of utilizing single-stimulus fMRI as a potential biologically based diagnostic tool to augment traditional clinical approaches.
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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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    New approaches to investigating social gestures in autism spectrum disorder
    Kishida, Kenneth T.; Li, Jian; Schwind, Justin; Montague, P. Read (BMC, 2012-05-24)
    The combination of economic games and human neuroimaging presents the possibility of using economic probes to identify biomarkers for quantitative features of healthy and diseased cognition. These probes span a range of important cognitive functions, but one new use is in the domain of reciprocating social exchange with other humans - a capacity perturbed in a number of psychopathologies. We summarize the use of a reciprocating exchange game to elicit neural and behavioral signatures for subjects diagnosed with autism spectrum disorder (ASD). Furthermore, we outline early efforts to capture features of social exchange in computational models and use these to identify quantitative behavioral differences between subjects with ASD and matched controls. Lastly, we summarize a number of subsequent studies inspired by the modeling results, which suggest new neural and behavioral signatures that could be used to characterize subtle deficits in information processing during interactions with other humans.
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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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    Searching for quantitative biomarkers of ASD using computational approaches and rapid assessment fMRI
    Kishida, Kenneth T. (2012-10-12)
    Kenneth Kishida, a research scientist at the Virginia Tech Carilion Research Institute, proposes the use of functional Magnetic Resonance Imaging assays for classifying neural subtypes of children with autism spectrum disorders.
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    Sub-second Dopamine and Serotonin Signaling in Human Striatum during Perceptual Decision-Making
    Bang, Dan; Kishida, Kenneth T.; Lohrenz, Terry; Tatter, Stephen B.; Fleming, Stephen M.; Montague, P. Read (CellPress, 2020-12-09)
    Recent animal research indicates that dopamine and serotonin, neuromodulators traditionally linked to appetitive and aversive processes, are also involved in sensory inference and decisions based on such inference. We tested this hypothesis in humans by monitoring sub-second striatal dopamine and serotonin signaling during a visual motion discrimination task that separates sensory uncertainty from decision difficulty in a factorial design. Caudate nucleus recordings (n = 4) revealed multi-scale encoding: in three participants, serotonin tracked sensory uncertainty, and, in one participant, both dopamine and serotonin tracked deviations from expected trial transitions within our factorial design. Putamen recordings (n = 1) supported a cognitionaction separation between caudate nucleus and putamen—a striatal sub-division unique to primates—with both dopamine and serotonin tracking decision times. These first-of-their-kind observations in the human brain reveal a role for sub-second dopamine and serotonin signaling in non-reward-based aspects of cognition and action.
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    Sub-Second Dopamine Detection in Human Striatum
    Kishida, Kenneth T.; Sandberg, Stefan G.; Lohrenz, Terry; Comair, Youssef G.; Sáez, Ignacio; Phillips, Paul E. M.; Montague, P. Read (PLOS, 2011-08-04)
    Fast-scan cyclic voltammetry at carbon fiber microelectrodes allows rapid (sub-second) measurements of dopamine release in behaving animals. Herein, we report the modification of existing technology and demonstrate the feasibility of making sub-second measurements of dopamine release in the caudate nucleus of a human subject during brain surgery. First, we describe the modification of our electrodes that allow for measurements to be made in a human brain. Next, we demonstrate in vitro and in vivo, that our modified electrodes can measure stimulated dopamine release in a rat brain equivalently to previously determined rodent electrodes. Finally, we demonstrate acute measurements of dopamine release in the caudate of a human patient during DBS electrode implantation surgery. The data generated are highly amenable for future work investigating the relationship between dopamine levels and important decision variables in human decisionmaking tasks.
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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.