Blunted anterior midcingulate response to reward in opioid users is normalized by prefrontal transcranial magnetic stimulation.

Introduction: Abnormalities in goal-directed behavior, mediated by mesocorticolimbic reward function and structure, contribute to worse clinical outcomes including higher risk of treatment dropout and drug relapse in opioid users (OU).

Material And Method: In a sham-controlled randomized study design, we measured whether robot-assisted 10Hz transcranial magnetic stimulation (TMS) applied to the prefrontal cortex was able to modulate anterior midcingulate cortex (MCC) electrophysiological response to rewards, in OU and matched healthy controls.

Results: We show that OU exhibit a blunted anterior MCC reward response, compared to healthy controls (t(39) = 2.

Recording Neural Reward Signals in a Naturalistic Operant Task Using Mobile-EEG and Augmented Reality.

The electrophysiological response to rewards recorded during laboratory tasks has been well documented, yet little is known about the neural response patterns in a more naturalistic setting. Here, we combined a mobile-EEG system with an augmented reality headset to record event-related brain potentials (ERPs) while participants engaged in a naturalistic operant task to find rewards. Twenty-five participants were asked to navigate toward a west or east goal location marked by floating orbs, and once participants reached the goal location, the orb would then signify a reward (5 cents) or no-reward (0 cents) outcome.

Oscillatory correlates of threat imminence during virtual navigation.

The Predatory Imminence Continuum Theory proposes that defensive behaviors depend on the proximity of a threat. While the neural mechanisms underlying this proposal are well studied in animal models, it remains poorly understood in humans. To address this issue, we recorded EEG from 24 (15 female) young adults engaged in a first-person virtual reality Risk-Reward interaction task.

Recording neural reward signals in the real-world using mobile-EEG and augmented reality.

The electrophysiological response to rewards recorded during laboratory-based tasks has been well documented over the past two decades, yet little is known about the neural response patterns in 'real-world' settings. To address this issue, we combined a mobile-EEG system with an augmented reality headset (which blends high definition "holograms" within the real-world) to record event-related brain potentials (ERP) while participants navigated an operant chamber to find rewards. 25 participants (age = 18-43, Male=6, Female=19) were asked to choose between two floating holograms marking a west or east goal-location in a large room, and once participants reached the goal location, the hologram would turn into a reward (5 cents) or no-reward (0 cents) cue.

Prefrontal transcranial magnetic stimulation boosts response vigour during reinforcement learning in healthy adults.

A 10-Hz repetitive transcranial magnetic stimulation to the left dorsal lateral prefrontal cortex has been shown to increase dopaminergic activity in the dorsal striatum, a region strongly implicated in reinforcement learning. However, the behavioural influence of this effect remains largely unknown. We tested the causal effects of 10-Hz stimulation on behavioural and computational characteristics of reinforcement learning.

Scalp recorded theta activity is modulated by reward, direction, and speed during virtual navigation in freely moving humans.

Theta oscillations (~ 4-12 Hz) are dynamically modulated by speed and direction in freely moving animals. However, due to the paucity of electrophysiological recordings of freely moving humans, this mechanism remains poorly understood. Here, we combined mobile-EEG with fully immersive virtual-reality to investigate theta dynamics in 22 healthy adults (aged 18-29 years old) freely navigating a T-maze to find rewards.

Recovery of reward function in problematic substance users using a combination of robotics, electrophysiology, and TMS.

Background: Theoretical and empirical work suggest that addictive drugs potentiate dopaminergic reinforcement learning signals and disrupt the reward function of its neural targets, including the anterior midcingulate cortex (aMCC) and the basal ganglia. Here, we aim to use prefrontal 10-Hz TMS to enhance aMCC reward activity and reward learning by the basal ganglia in problematic substance users.

Methods: 22 problematic substance users were randomized into an Active and SHAM (coil flipped) TMS group.

Beyond the Motor Cortex: Theta Burst Stimulation of the Anterior Midcingulate Cortex.

Background: While the facilitatory and inhibitory effects of intermittent theta burst stimulation (iTBS) and continuous TBS (cTBS) protocols have been well documented on motor physiology, the action of TBS protocols on prefrontal functioning remain unclear. Here we asked whether iTBS or cTBS can differentially modulate reward-related signaling in the anterior midcingulate cortex (aMCC).

Methods: Across 2 experiments, we used a robot-assisted transcranial magnetic stimulation system, combined with electroencephalogram recordings, to investigate the aftereffects of prefrontal iTBS and cTBS on the reward positivity, an electrophysiological signal believed to index sensitivity of the aMCC to rewards.

Social context effects on error-related brain activity are dependent on interpersonal and achievement-related traits.

Brain correlates of performance monitoring, such as the Error-Related Negativity (ERN), are considerably influenced by situational factors. For instance, errors committed during social interaction typically elicit enhanced ERNs. While individual differences in ERN magnitude have been implicated in a wide variety of psychopathologies, it remains unclear how individual dispositions may interact with situational incentives to influence performance monitoring.

Neurobehavioral correlates of obesity are largely heritable.

Recent molecular genetic studies have shown that the majority of genes associated with obesity are expressed in the central nervous system. Obesity has also been associated with neurobehavioral factors such as brain morphology, cognitive performance, and personality. Here, we tested whether these neurobehavioral factors were associated with the heritable variance in obesity measured by body mass index (BMI) in the Human Connectome Project ( = 895 siblings).

Smoking Decisions: Altered Reinforcement Learning Signals Induced by Nicotine State.

Introduction: Alterations in dopamine signaling play a key role in reinforcement learning and nicotine addiction, but the relationship between these two processes has not been well characterized. We investigated this relationship in young adult smokers using a combination of behavioral and computational measures of reinforcement learning.

Methods: We asked moderately dependent smokers to engage in a reinforcement learning task three times: smoking as usual, smoking abstinence, and cigarette consumption.

Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence.

Background: Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both.

Methods: In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age.

Reversing the Atypical Valuation of Drug and Nondrug Rewards in Smokers Using Multimodal Neuroimaging.

Background: Chronic substance use can disrupt the reward function of the anterior cingulate cortex (ACC), biasing the ACC to favor goal-directed behaviors that converge on drug use. Here we used multimodal neuroimaging methods to ask whether modulating reward-related signaling in the ACC can reverse the atypical valuation of nondrug and drug rewards in abstinent smokers.

Methods: We first recorded functional magnetic resonance imaging data from 20 moderately dependent cigarette smokers (mean age = 25 years; no history of neuropsychiatric disorders), following an overnight period of abstinence, to identify regions of the left dorsal lateral prefrontal cortex associated with the anticipation of drug-related rewards (cigarette puff).

It's all about timing: An electrophysiological examination of feedback-based learning with immediate and delayed feedback.

Feedback regarding an individual's action can occur immediately or with a temporal delay. Processing of feedback that varies in its delivery time is proposed to engage different brain mechanisms. fMRI data implicate the striatum in the processing of immediate feedback, and the medial temporal lobe (MTL) in the processing of delayed feedback.

Effects of delaying binge drinking on adolescent brain development: a longitudinal neuroimaging study.

Background: Onset of alcohol use by 14 relative to 21 years of age strongly predicts elevated risk for severe alcohol use problems, with 27% versus 4% of individuals exhibiting alcohol dependence within 10 years of onset. What remains unclear is whether this early alcohol use (i) is a marker for later problems, reflected as a pre-existing developmental predisposition, (ii) causes global neural atrophy or (iii) specifically disturbs neuro-maturational processes implicated in addiction, such as executive functions or reward processing. Since our group has demonstrated that a novel intervention program targeting personality traits associated with adolescent alcohol use can prevent the uptake of drinking and binge drinking by 40 to 60%, a crucial question is whether prevention of early onset alcohol misuse will protect adolescent neurodevelopment and which domains of neurodevelopment can be protected.

Oscillatory profiles of positive, negative and neutral feedback stimuli during adaptive decision making.

The electrophysiological response to positive and negative feedback during reinforcement learning has been well documented over the past two decades, yet, little is known about the neural response to uninformative events that often follow our actions. To address this issue, we recorded the electroencephalograph (EEG) during a time-estimation task using both informative (positive and negative) and uninformative (neutral) feedback. In the time-frequency domain, uninformative feedback elicited significantly less induced beta-gamma activity than informative feedback.

Atypical valuation of monetary and cigarette rewards in substance dependent smokers.

Objective: Substance dependent (SD) relative to non-dependent (ND) individuals exhibit an attenuated reward positivity, an electrophysiological signal believed to index sensitivity of anterior cingulate cortex (ACC) to rewards. Here we asked whether this altered neural response reflects a specific devaluation of monetary rewards relative to drug-related rewards by ACC.

Methods: We recorded the reward positivity from SD and ND individuals who currently smoke, following an overnight period of abstinence, while they engaged in two feedback tasks.

Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse.

The development and expression of the midbrain dopamine system is determined in part by genetic factors that vary across individuals such that dopamine-related genes are partly responsible for addiction vulnerability. However, a complete account of how dopamine-related genes predispose individuals to drug addiction remains to be developed. Adopting an intermediate phenotype approach, we investigated whether reward-related electrophysiological activity of ACC-a cortical region said to utilize dopamine reward signals to learn the value of extended, context-specific sequences of goal-directed behaviors-mediates the influence of multiple dopamine-related functional polymorphisms over substance use.

Rightward-biased hemodynamic response of the parahippocampal system during virtual navigation.

Phase reset of parahippocampal electrophysiological oscillations in the theta frequency range is said to contribute to item encoding and retrieval during spatial navigation. Although well-studied in non-human animals, this mechanism is poorly understood in humans. Previously we found that feedback stimuli presented in a virtual maze environment elicited a burst of theta power over right-posterior areas of the human scalp, and that the power and phase angle of these oscillations were greater following right turns compared to left turns in the maze.

The topographical N170: electrophysiological evidence of a neural mechanism for human spatial navigation.

We recently demonstrated that the latency of a component of the event-related brain potential, the topographical N170 (NT170), is sensitive to the spatial location of reward-related stimuli in a virtual maze environment, occurring earlier for rewards found following rightward turns compared to leftward turns. We suggested that this NT170 latency effect may result from phase reset of an ongoing theta rhythm by a parahippocampal system for spatial navigation. Here we tested several predictions that follow from this proposal, namely, that the effect is observed only when the rewards are presented in a spatial environment, that it is sensitive to individual differences in spatial ability, that it is localizable to the right parahippocampal region, and that it is consistent with partial phase resetting of an ongoing theta rhythm.

Constraints on decision making: implications from genetics, personality, and addiction.

An influential neurocomputational theory of the biological mechanisms of decision making, the "basal ganglia go/no-go model," holds that individual variability in decision making is determined by differences in the makeup of a striatal system for approach and avoidance learning. The model has been tested empirically with the probabilistic selection task (PST), which determines whether individuals learn better from positive or negative feedback. In accordance with the model, in the present study we examined whether an individual's ability to learn from positive and negative reinforcement can be predicted by genetic factors related to the midbrain dopamine system.