Emotional words evoke region- and valence-specific patterns of concurrent neuromodulator release in human thalamus and cortex.

Words represent a uniquely human information channel-humans use words to express thoughts and feelings and to assign emotional valence to experience. Work from model organisms suggests that valence assignments are carried out in part by the neuromodulators dopamine, serotonin, and norepinephrine. Here, we ask whether valence signaling by these neuromodulators extends to word semantics in humans by measuring sub-second neuromodulator dynamics in the thalamus (N = 13) and anterior cingulate cortex (N = 6) of individuals evaluating positive, negative, and neutrally valenced words.

Comparison of dopamine release and uptake parameters across sex, species and striatal subregions.

For over four decades, fast-scan cyclic voltammetry (FSCV) has been used to selectively measure neurotransmitters such as dopamine (DA) with high spatial and temporal resolution, providing detailed information about the regulation of DA in the extracellular space. FSCV is an optimal method for determining concentrations of stimulus-evoked DA in brain tissue. When modelling diseases involving disturbances in DA transmission, preclinical rodent models are especially useful because of the availability of specialized tools and techniques that serve as a foundation for translational research.

Multiomic foundations of human prefrontal cortex tissue function.

The prefrontal cortex (PFC) is a region of the brain that in humans is involved in the production of higher-order functions such as cognition, emotion, perception, and behavior. Neurotransmission in the PFC produces higher-order functions by integrating information from other areas of the brain. At the foundation of neurotransmission, and by extension at the foundation of higher-order brain functions, are an untold number of coordinated molecular processes involving the DNA sequence variants in the genome, RNA transcripts in the transcriptome, and proteins in the proteome.

Maximizing Electrochemical Information: A Perspective on Background-Inclusive Fast Voltammetry.

This perspective encompasses a focused review of the literature leading to a tipping point in electroanalytical chemistry. We tie together the threads of a "revolution" quietly in the making for years through the work of many authors. Long-held misconceptions about the use of background subtraction in fast voltammetry are addressed.

Subjective feelings associated with expectations and rewards during risky decision-making in impulse control disorder.

Impulse Control Disorder (ICD) in Parkinson's disease is a behavioral addiction induced by dopaminergic therapies, but otherwise unclear etiology. The current study investigates the interaction of reward processing variables, dopaminergic therapy, and risky decision-making and subjective feelings in patients with versus without ICD. Patients with (n = 18) and without (n = 12) ICD performed a risky decision-making task both 'on' and 'off' standard-of-care dopaminergic therapies (the task was performed on 2 different days with the order of on and off visits randomized for each patient).

Dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange.

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.

Sub-second and multi-second dopamine dynamics underlie variability in human time perception.

Timing behaviour and the perception of time are fundamental to cognitive and emotional processes in humans. In non-human model organisms, the neuromodulator dopamine has been associated with variations in timing behaviour, but the connection between variations in dopamine levels and the human experience of time has not been directly assessed. Here, we report how dopamine levels in human striatum, measured with sub-second temporal resolution during awake deep brain stimulation surgery, relate to participants' perceptual judgements of time intervals.

Subsecond fluctuations in extracellular dopamine encode reward and punishment prediction errors in humans.

In the mammalian brain, midbrain dopamine neuron activity is hypothesized to encode reward prediction errors that promote learning and guide behavior by causing rapid changes in dopamine levels in target brain regions. This hypothesis (and alternatives regarding dopamine's role in punishment-learning) has limited direct evidence in humans. We report intracranial, subsecond measurements of dopamine release in human striatum measured, while volunteers (i.

Noradrenaline tracks emotional modulation of attention in human amygdala.

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.

Sub-second Dopamine Signals during Risky Decision-Making in Patients with Impulse Control Disorder.

Background: Impulse Control Disorder (ICD) in Parkinson's disease is a behavioral addiction arising secondary to dopaminergic therapies, most often dopamine receptor agonists. Prior research implicates changes in striatal function and heightened dopaminergic activity in the dorsal striatum of patients with ICD. However, this prior work does not possess the temporal resolution required to investigate dopaminergic signaling during real-time progression through various stages of decision-making involving anticipation and feedback.

Time perception reflects individual differences in motor and non-motor symptoms of Parkinson's disease.

Decreasing dopaminergic function is at the core of Parkinson's disease (PD) motor symptoms and changes in dopaminergic action are associated with many comorbid non-motor symptoms in PD. Notably, dopaminergic signaling in the striatum has been shown to play a critical role in the perception of time. We hypothesize that patients with PD perceive time differently and in accordance with their specific comorbid non-motor symptoms and clinical state.

Valence-partitioned learning signals drive choice behavior and phenomenal subjective experience in humans.

How the human brain generates conscious phenomenal experience is a fundamental problem. In particular, it is unknown how variable and dynamic changes in subjective affect are driven by interactions with objective phenomena. We hypothesize a neurocomputational mechanism that generates valence-specific learning signals associated with 'what it is like' to be rewarded or punished.

Time perception reflects individual differences in motor and non-motor symptoms of Parkinson's disease.

Unlabelled: Dopaminergic signaling in the striatum has been shown to play a critical role in the perception of time. Decreasing striatal dopamine efficacy is at the core of Parkinson's disease (PD) motor symptoms and changes in dopaminergic action have been associated with many comorbid non-motor symptoms in PD. We hypothesize that patients with PD perceive time differently and in accordance with their specific comorbid non-motor symptoms and clinical state.

Intracranial subsecond dopamine measurements during a "sure bet or gamble" decision-making task in patients with alcohol use disorder suggest diminished dopaminergic signals about relief.

Objective: To the authors' knowledge, no data have been reported on dopamine fluctuations on subsecond timescales in humans with alcohol use disorder (AUD). In this study, dopamine release was monitored in 2 patients with and 2 without a history of AUD during a "sure bet or gamble" (SBORG) decision-making task to begin to characterize how subsecond dopamine responses to counterfactual information, related to psychological notions of regret and relief, in AUD may be altered.

Methods: Measurements of extracellular dopamine levels were made once every 100 msec using human voltammetric methods.

Hierarchical resampling for bagging in multistudy prediction with applications to human neurochemical sensing.

We propose the "study strap ensemble", which combines advantages of two common approaches to fitting prediction models when multiple training datasets ("studies") are available: pooling studies and fitting one model versus averaging predictions from multiple models each fit to individual studies. The study strap ensemble fits models to bootstrapped datasets, or "pseudo-studies." These are generated by resampling from multiple studies with a hierarchical resampling scheme that generalizes the randomized cluster bootstrap.

Intracranial approach for sub-second monitoring of neurotransmitters during DBS electrode implantation does not increase infection rate.

Introduction: Currently, sub-second monitoring of neurotransmitter release in humans can only be performed during standard of care invasive procedures like DBS electrode implantation. The procedure requires acute insertion of a research probe and additional time in surgery, which may increase infection risk. We sought to determine the impact of our research procedure, particularly the extended time in surgery, on infection risk.

Sub-second Dopamine and Serotonin Signaling in Human Striatum during Perceptual Decision-Making.

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.

Diminished single-stimulus response in vmPFC to favorite people in children diagnosed with Autism Spectrum Disorder.

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.

Computational Underpinnings of Neuromodulation in Humans.

We summarize a new approach to neuromodulator detection that provides colocalized detection of dopamine, serotonin, and norepinephrine at subsecond timescales and promises to provide submillisecond estimates of the same. The methodology, elastic net electrochemistry, is used to estimate dopamine and serotonin in the striatum of conscious human subjects during active decision-making. We show a proof-of-principle example of the same method working on commercially available depth electrodes in common use for epilepsy monitoring and neurosurgical planning in humans, which further promises to make such electrodes sources of fast neuromodulator information never before available in human subjects.

The Protective Action Encoding of Serotonin Transients in the Human Brain.

The role of serotonin in human brain function remains elusive due, at least in part, to our inability to measure rapidly the local concentration of this neurotransmitter. We used fast-scan cyclic voltammetry to infer serotonergic signaling from the striatum of 14 brains of human patients with Parkinson's disease. Here we report these novel measurements and show that they correlate with outcomes and decisions in a sequential investment game.

An efficiency framework for valence processing systems inspired by soft cross-wiring.

Recent experiments suggest that subsecond dopamine delivery to human striatum encodes a combination of reward prediction errors and counterfactual errors thus composing the actual with the possible into one neurochemical signal. Here, we present a model where the counterfactual part of these striatal dopamine fluctuations originates in another valuation system that shadows the dopamine system by acting as its near-antipode in terms of spike-rate encoding yet co-releases dopamine alongside its own native neurotransmitter. We show that such a hypothesis engenders important representational consequences where valence processing appears subject to the efficient encoding considerations common to the visual and auditory systems.

BOLD and its connection to dopamine release in human striatum: a cross-cohort comparison.

Activity in midbrain dopamine neurons modulates the release of dopamine in terminal structures including the striatum, and controls reward-dependent valuation and choice. This fluctuating release of dopamine is thought to encode reward prediction error (RPE) signals and other value-related information crucial to decision-making, and such models have been used to track prediction error signals in the striatum as encoded by BOLD signals. However, until recently there have been no comparisons of BOLD responses and dopamine responses except for one clear correlation of these two signals in rodents.

Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward.

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.