Lack of effect of methamphetamine on reward-related brain activity in healthy adults.

INTRODUCTION: Stimulant drugs are thought to alter processing of rewarding stimuli. However, the mechanisms by which they do this are not fully understood. METHOD: In this study we used EEG to assess effects of single doses of methamphetamine (MA) on neural responses during anticipation and receipt of reward in healthy volunteers. Healthy young men and women (N = 28) completed three sessions in which they received placebo, a low MA dose (10 mg) or a higher MA dose (20 mg) under double blind conditions. Subjective and cardiovascular measures were obtained, and EEG was used to assess brain activity during an electrophysiological version of the Monetary Incentive Delay (eMID) task. RESULTS: EEG measures showed expected patterns during anticipation and receipt of reward, and MA produced its expected effects on mood and cardiovascular function. However, MA did not affect EEG responses during either anticipation or receipt of rewards. CONCLUSIONS: These findings suggest that the effects of MA on EEG signals of reward processing are subtle, and not related to the drug's effects on subjective feelings of well-being. The findings contribute to our understanding of the neural effects of MA during behaviors related to reward.

Electrophysiological evidence of mal-adaptation to error in remitted depression.

Identifying risk markers for major depressive disorder (MDD) that persist into remission is key to address MDD's high rate of recurrence. Central to MDD recurrence are the disorder's negative information processing biases, such as heightened responses to errors, which may subsequently impair abilities to monitor performance and adjust behaviors based on environmental demands. However, little is known regarding the neurophysiological correlates of post-error adaptation in depression. The current study investigated event-related potentials (ERPs) and behavioral performance following errors from a flanker task in 58 participants with remitted MDD (rMDD) and 118 healthy controls (HC). Specifically, using trial-level data, we tested: (a) the impact of errors on response-locked ERPs of the current and post-error trials (error-related negativity [ERN] and correct response negativity [CRN]) and (b) longer-term adaptation to errors (ERN/CRN) over the course of the task. Compared to HC, rMDD participants showed a larger ERN to the current trial and smaller habituation in ERN over time. On trials immediately following errors, rMDD participants showed slower reaction times that were predicted by the previous-trial ERN amplitude but comparable accuracy to HC, suggesting a deficient ability to disengage from errors and/or a compensatory effort to mitigate accuracy decrements. Critically, this pattern of responding: (a) was concurrently associated with greater levels of anhedonia symptoms, more severe MDD history, and interpersonal impairment (but lower impairment in life activities) and (b) predicted more anhedonia symptoms at one-year follow-up. Collectively, a hyperactive performance monitoring system may be a useful risk marker for future MDD recurrence.

Neural responsiveness to reward and suicidal ideation in social anxiety and major depression before and after psychotherapy.

Suicidality is prevalent in Social Anxiety Disorder (SAD) and Major Depressive Disorder (MDD). Limited data indicate the reward positivity (RewP), a neurophysiological index of reward responsivity, and subjective capacity for pleasure may serve as brain and behavioral assays for suicide risk though this has yet to be examined in SAD or MDD in the context of psychotherapy. Therefore, the current study tested whether suicidal ideation (SI) relates to RewP and subjective capacity for anticipatory and consummatory pleasure at baseline and whether Cognitive Behavioral Therapy (CBT) impacts these measures. Participants with SAD (n = 55) or MDD (n = 54) completed a monetary reward task (gains vs. losses) during electroencephalogram (EEG) before being randomized to CBT or supportive therapy (ST), a comparator common factors arm. EEG and SI data were collected at baseline, mid-treatment, and post-treatment; capacity for pleasure was collected at baseline and post-treatment. Baseline results showed participants with SAD or MDD were comparable in SI, RewP, and capacity for pleasure. When controlling for symptom severity, SI negatively corresponded with RewP following gains and SI positively corresponded with RewP following losses at baseline. Yet, SI did not relate to subjective capacity for pleasure. Evidence of a distinct SI-RewP association suggests RewP may serve as a transdiagnositic brain-based marker of SI. Treatment outcome revealed that among participants with SI at baseline, SI significantly decreased regardless of treatment arm; also, consummatory, but not anticipatory, pleasure increased across participants regardless of treatment arm. RewP was stable following treatment, which has been reported in other clinical trial studies.

Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity.

Renewed interest in classic psychedelics as treatments for psychiatric disorders warrants a deeper understanding of their neural mechanisms. Single, high doses of psychedelic drugs have shown promise in treating depressive disorders, perhaps by reversing deficits in reward processing in the brain. In addition, there are anecdotal reports that repeated ingestion of low doses of LSD, or "microdosing", improve mood, cognition, and feelings of wellbeing. However, the effects of low doses of classic psychedelics on reward processing have not been studied. The current study examined the effects of two single, low doses of LSD compared to placebo on measures of reward processing. Eighteen healthy adults completed three sessions in which they received placebo (LSD-0), 13 µg LSD (LSD-13) and 26 µg LSD (LSD-26) in a within-subject, double-blind design. Neural activity was recorded while participants completed the electrophysiological monetary incentive delay task. Event-related potentials were measured during feedback processing (Reward-Positivity: RewP, Feedback-P3: FB-P3, and Late-Positive Potential: LPP). Compared to placebo, LSD-13 increased RewP and LPP amplitudes for reward (vs. neutral) feedback, and LSD-13 and LSD-26 increased FB-P3 amplitudes for positive (vs. negative) feedback. These effects were unassociated with most subjective measures of drug effects. Thus, single, low doses of LSD (vs. placebo) increased three reward-related ERP components reflecting increased hedonic (RewP), motivational (FB-P3), and affective processing of feedback (LPP). These results constitute the first evidence that low doses of LSD increase reward-related brain activity in humans. These findings may have important implications for the treatment of depressive disorders.

Δ9-THC reduces reward-related brain activity in healthy adults.

RATIONALE: Greater availability of cannabis in the USA has raised concerns about adverse effects of the drug, including possible amotivational states. Lack of motivation may be assessed by examining acute effects of cannabinoids on reward processing. OBJECTIVES: This study examined single doses of delta-9-tetrahydrocannabinol (∆9-THC; 7.5, 15 mg oral) in healthy adults using a version of the monetary incentive delay (MID) task adapted for electroencephalography (EEG; e-MID) in a within-subjects, double blind design. METHODS: Two phases of reward processing were examined: anticipation, which occurs with presentation of cues that indicate upcoming reward, punishment, or neutral conditions, and outcome, which occurs with feedback indicating hits or misses. During anticipation, we measured two event-related potential (ERP) components: the P300, which measures attention and motivation, and the LPP, which measures affective processing. During outcome processing, we measured P300 and LPP, as well as the RewP, which measures outcome evaluation. RESULTS: We found that ∆9-THC modulated outcome processing, but not reward anticipation. Specifically, both doses of ∆9-THC (7.5 and 15 mg) reduced RewP amplitudes after outcome feedback (hits and misses) relative to placebo. ∆9-THC (15 mg) also reduced P300 and LPP amplitudes following hits compared to misses, relative to both placebo and 7.5 mg ∆9-THC. CONCLUSIONS: These findings suggest that ∆9-THC dampens responses to both reward and loss feedback, which may reflect an "amotivational" state. Future studies are needed to determine generalizability of this effect, such as its pharmacological specificity and its specificity to monetary vs other types of reward.

Neural mechanisms of motor dysfunction in individuals at clinical high-risk for psychosis: Evidence for impairments in motor activation.

Motor abnormalities are a core feature of psychotic disorders observed from the premorbid period through chronic illness, suggesting motor dysfunction may reflect the pathophysiology of psychosis. Electrophysiology research in schizophrenia suggests impaired motor activation and preparation may underlie these motor abnormalities. Despite behavioral studies suggesting similar motor dysfunction in those at clinical high-risk (CHR) for psychosis, there have been no studies examining neural mechanisms of motor dysfunction in the CHR period, where research can inform pathophysiological and risk models. The present study used the lateralized readiness potential (LRP), an event-related potential index of motor activation and preparation, to examine mechanisms of motor dysfunction in 42 CHR and 41 control participants (N = 83, 56% female). Response competition was manipulated to determine whether deficits are secondary to cognitive control impairments or reflect primary motor deficits. Behaviorally, CHR participants exhibited overall slower responses than controls. Further, relative to controls, CHR participants showed reduced activation of correct but not incorrect responses, reflected in blunted LRP amplitude under weak response competition and no difference in amplitude associated with the incorrect response under strong response competition. This pattern of results suggests individuals at CHR for psychosis exhibit primary motor deficits in activating and preparing behavioral responses and are contrary to a deficit in cognitive control. Further, blunted LRP amplitude was associated with worsening of negative symptoms at 12-month follow-up. Together, these findings are consistent with LRP studies in psychosis and implicate motor activation deficits as potential mechanisms of motor dysfunction in the high-risk period. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Outcome valence and stimulus frequency affect neural responses to rewards and punishments.

The Reward-Positivity (RewP) is a frontocentral event-related potential elicited following reward and punishment feedback. Reinforcement learning theories propose the RewP reflects a reward prediction error that increases following more favorable (vs. unfavorable) outcomes. An alternative perspective, however, proposes this component indexes a salience-prediction error that increases following more salient outcomes. Evidence from prior studies that included both reward and punishment conditions is mixed, supporting both accounts. However, these studies often varied how feedback stimuli were repeated across reward and punishment conditions. Differences in the frequency of feedback stimuli may drive inconsistencies by introducing salience effects for infrequent stimuli regardless of whether they are associated with rewards or punishments. To test this hypothesis, the current study examined the effect of outcome valence and stimulus frequency on the RewP and neighboring P2 and P3 components in reward, punishment, and neutral contexts across two separate experiments that varied how often feedback stimuli were repeated between conditions. Experiment 1 revealed infrequent feedback stimuli generated overlapping positivity across all three components. However, controlling for stimulus frequency, experiment 2 revealed favorable outcomes that increased RewP and P3 positivity. Together, these results suggest the RewP reflects some combination of reward- and salience-prediction error encoding. Results also indicate infrequent feedback stimuli elicited strong salience effects across all three components that may inflate, eliminate, or reverse outcome valence effects for the RewP and P3. These results resolve several inconsistencies in the literature and have important implications for electrocortical investigations of reward and punishment feedback processing.

DRD4 polymorphisms modulate reward positivity and P3a in a gambling task: Exploring a genetic basis for cultural learning.

Prior work shows that people respond more plastically to environmental influences, including cultural influences, if they carry the 7 or 2-repeat (7/2R) allelic variant of the dopamine D4 receptor gene (DRD4). The 7/2R carriers are thus more likely to endorse the norms and values of their culture. So far, however, mechanisms underlying this moderation of cultural acquisition by DRD4 are unclear. To address this gap in knowledge, we tested the hypothesis that DRD4 modulates the processing of reward cues existing in the environment. About 72 young adults, preselected for their DRD4 status, performed a gambling task, while the electroencephalogram was recorded. Principal components of event-related potentials aligned to the Reward-Positivity (associated with bottom-up processing of reward prediction errors) and frontal-P3 (associated with top-down attention) were both significantly more positive following gains than following losses. As predicted, the gain-loss differences were significantly larger for 7/2R carriers than for noncarriers. Also, as predicted, the cultural backgrounds of the participants (East Asian vs. European American) did not moderate the effects of DRD4. Our findings suggest that the 7/2R variant of DRD4 enhances (a) the detection of reward prediction errors and (b) controlled attention that updates the context for the reward, thereby suggesting one possible mechanism underlying the DRD4 × Culture interactions.

Emotional content impacts how executive function ability relates to willingness to wait and to work for reward.

Research has demonstrated that better value-based decision making (e.g., waiting or working for rewards) relates to greater executive function (EF) ability. However, EF is not a static ability, but is influenced by the emotional content of the task. As such, EF ability in emotional contexts may have unique associations with value-based decision making, in which costs and benefits are explicit. Participants (N = 229) completed an EF task (with both negative and neutral task conditions) and two value-based decision-making tasks. Willingness to wait and to work were evaluated in separate path models relating the waiting and working conditions to the EF conditions. Willingness to wait and willingness to work showed distinct relationships with EF ability: Greater EF ability on a negative, but not on a neutral, EF task was related to a willingness to wait for a reward, whereas greater EF ability across both EF tasks was related to a greater willingness to work for a reward. EF ability on a negative EF task showed an inverted-U relationship to willingness to wait for reward, and was most related to willingness to wait at a 6-month delay. Greater EF, regardless of whether the task was negative or neutral, was related to a greater willingness to work when reward was uncertain (50%) or was likely (88%), but not when reward was unlikely (12%). This study suggests that the emotional content of value-based decisions impacts the relationship between EF ability and willingness to wait or to work for reward.

Shifts in attentional scope modulate event-related potentials evoked by reward.

Emotions broaden or narrow the scope of attention in order to facilitate adaptive responses in threatening and rewarding contexts. In the current study, rather than asking how emotions influence attentional scope, we considered the possibility that the relationship between attentional breadth and emotion is bidirectional by asking whether shifts in attentional scope alter emotional processes using an event-related potential (ERP) paradigm. Participants (N = 30) completed a modified version of a Monetary Incentive Delay (MID) task, wherein their attention was either narrowed or broadened as they attempted to win rewards. Behaviorally, narrowing attention improved task performance in the form of reduced errors and increased monetary winnings. During cue processing, narrowing (compared to broadening) attention reduced the Cue-P3 (irrespective of cue type). During feedback processing, narrowing (compared to broadening) attention reduced the Feedback-P3 to monetary wins and increased the Feedback-P2 and the Feedback-P3 to monetary non-wins. Results highlight complexity and bidirectionality in the relationship between attentional scope and affective processes.

Hypomania and depression associated with distinct neural activity for immediate and future rewards.

Bipolar spectrum and unipolar depressive disorders have been associated with distinct and opposite profiles of reward-related neural activity. These opposite profiles may reflect a differential preexisting vulnerability for both types of disorders. In support, recent ERP studies find that, following reward feedback, a larger reward positivity (RewP) is associated with greater vulnerability for bipolar spectrum disorders, whereas a smaller RewP is associated with greater vulnerability for depression. However, prior studies have investigated only immediate rewards and have not examined dimensions of both bipolar disorder and unipolar depression within the same sample. The present study is the first to investigate feedback-related ERP correlates of proneness to hypomania and unipolar depressive tendencies within the same sample and to expand our scope to include future rewards. Participants completed a modified time estimation task where the same monetary reward was available immediately or at one of five different future dates. Results revealed proneness to hypomania and unipolar depressive tendencies were related to an elevated and blunted RewP, respectively, but only following immediate rewards (i.e., today). Following rewards in the distant future (e.g., 8 months), proneness to hypomania and depressive tendencies were associated with elevated and blunted amplitudes for the P3, respectively, a subsequent ERP component reflecting motivational salience during extended feedback processing. Furthermore, these opposing profiles were independent of, and significantly different from, one another. These results suggest that feedback-related ERPs following immediate and future rewards are candidate biomarkers that can physiologically separate vulnerability for bipolar spectrum from unipolar depressive disorders.

Reappraisal and suppression emotion-regulation tendencies differentially predict reward-responsivity and psychological well-being.

Individuals who suppress their emotions experience less positive emotions, worse relationships, and a reduced quality of life whereas those who tend to reappraise show an opposite pattern. Despite this divergent pattern, few have asked how the use of these emotion-regulation strategies relates to reward responsivity. We predicted that elevated suppression would be associated with blunted reward responsivity, whereas reappraisal would be associated with elevated reward responsivity. To test this hypothesis, participants completed a measure of individual differences in emotion-regulation strategies, measures of self-reported reward responsivity, and then a reward time-estimation task (Kotani et al., 2003) while electroencephalography (EEG) was recorded. Results revealed that individual differences in cognitive reappraisal were unrelated to self-report measures of reward responsivity, whereas suppression was associated with blunted reward responsivity. At the neural level, reappraisal was associated with greater attention to the rewarding cues, as indexed by the P300 event-related potential (ERP) component, whereas suppression was related to blunted reward anticipation, as indexed by the stimulus-preceding negativity (SPN) ERP component. Suppression prospectively predicted worse psychological well-being 2.5 years later and blunted neural reward anticipation partially explained this association. Taken together with past research, these results suggest reappraisal tendencies may lead to better outcomes due, in part, to enhanced reward responsivity, whereas the negative consequences of suppression may be associated with blunted reward responsivity.

Beyond the FRN: Broadening the time-course of EEG and ERP components implicated in reward processing.

Most reward-related electroencephalogram (EEG) studies focus exclusively on the feedback-related negativity (FRN, also known as feedback negativity or FN, medial-frontal negativity or MFN, feedback error-related negativity or fERN, and reward positivity or RewP). This component is usually measured approximately 200-300 ms post-feedback at a single electrode in the frontal-central area (e.g., Fz or FCz). The present review argues that this singular focus on the FRN fails to leverage EEG's greatest strength, its temporal resolution, by underutilizing the rich variety of event-related potential (ERP) and EEG time-frequency components encompassing the wider temporal heterogeneity of reward processing. The primary objective of this review is to provide a comprehensive understanding of often overlooked ERP and EEG correlates beyond the FRN in the context of reward processing with the secondary goal of guiding future research toward multistage experimental designs and multicomponent analyses that leverage the temporal power of EEG. We comprehensively review reward-related ERPs (including the FRN, readiness potential or RP, stimulus-preceding negativity or SPN, contingent-negative variation or CNV, cue-related N2 and P3, Feedback-P3, and late-positive potential or LPP/slow-wave), and reward-related EEG time-frequency components (changes in power at alpha, beta, theta, and delta bands). These electrophysiological signatures display distinct time-courses, scalp topographies, and reflect independent psychological processes during anticipatory and/or outcome stages of reward processing. Special consideration is given to the time-course of each component and factors that significantly contribute to component variation. Concluding remarks identify current limitations along with recommendations for potential important future directions.

Suppression of error-preceding brain activity explains exaggerated error monitoring in females with worry.

Anxiety is consistently associated with hyperactive neural responses to errors. The majority of existing research has focused on a single marker of error-elicited brain activity-the error-related negativity (ERN), an event-related brain potential (ERP) elicited 50-100ms following an erroneous response. The ERN has accumulated growing interest for its use in clinical contexts as a potential biomarker and/or endophenotype. However, it is unknown whether anxiety's effects are specific to brain activity following erroneous responses; anxiety may affect processes prior to error commission, suggesting that the ERN might reflect the output of abnormal processing that begins before an error. Here, we examined the error-preceding positivity (EPP) - an ERP time-locked to the correct response immediately before errors - that reflects a gradual disengagement of task-focused attention preceding errors. Results revealed that female worriers demonstrated significantly attenuated EPP amplitude, indicating reduced pre-error disengagement. Moreover, reduced EPP mediated the relationship between worry and the enhanced ERN following errors. These results suggest that the temporal dynamics of anxiety's impact on error processing are more nuanced than previously thought such that effects emerge prior to the actual occurrence of an erroneous response.

Cultural shaping of neural responses: Feedback-related potentials vary with self-construal and face priming.

Previous work shows that when an image of a face is presented immediately prior to each trial of a speeded cognitive task (face-priming), the error-related negativity (ERN) is upregulated for Asians, but it is downregulated for Caucasians. These findings are consistent with the hypothesis that images of "generalized other" vary cross-culturally such that they evoke anxiety for Asians, whereas they serve as safety cues for Caucasians. Here, we tested whether the cross-cultural variation in the face-priming effect would be observed in a gambling paradigm. Caucasian Americans, Asian Americans, and Asian sojourners were exposed to a brief flash of a schematic face during a gamble. For Asian Americans, face-priming resulted in significant increases of both negative-going deflection of ERP upon negative feedback (feedback-related negativity [FRN]) and positive-going deflection of ERP upon positive feedback (feedback-related positivity [FRP]). For Caucasian Americans, face-priming showed a significant reversal, decreasing both FRN and FRP. The cultural difference in the face-priming effect in FRN and FRP was partially mediated by interdependent self-construal. Curiously, Asian sojourners showed a pattern similar to the one for Caucasian Americans. Our findings suggest that culture shapes neural pathways in both systematic and highly dynamic fashion.

Attention deficit hyperactivity disorder and the athlete: an American Medical Society for Sports Medicine position statement.

Attention deficit hyperactivity disorder (ADHD) is an important issue for the physician taking care of athletes since ADHD is common in the athletic population, and comorbid issues affect athletes of all ages. The health care provider taking care of athletes should be familiar with making the diagnosis of ADHD, the management of ADHD, and how treatment medications impact exercise and performance. In this statement, the term "Team Physician" is used in reference to all healthcare providers that take care of athletes. These providers should understand the side effects of medications, regulatory issues regarding stimulant medications, and indications for additional testing. This position statement is not intended to be a comprehensive review of ADHD, but rather a directed review of the core issues related to the athlete with ADHD.

Awareness of altitude sickness among visitors to a North American ski resort.

OBJECTIVE: To quantify awareness of acute mountain sickness (AMS) in a sample of visitors to a North American ski resort and to identify strategies and interest for increasing knowledge of AMS in that population. METHODS: One hundred and thirty visitors to Big Sky Ski Resort, Montana, were surveyed. Demographic data were obtained. Respondents were asked about their current knowledge of AMS and then answered questions designed to quantify their depth of knowledge of the subject. Correct answers were correlated with demographic data. Respondents also answered questions indicating their interest in further education about altitude illness and their preferred modality for obtaining this information. RESULTS: In general, most respondents were young, 18 to 30 years (62.3%), and male (62.5%). Seventy-six percent had at least some college education and more than 5 years of skiing/snowboarding experience. Only 55% of respondents had some knowledge of AMS, but only 30% had knowledge of AMS symptoms using the Lake Louise Scoring System. About 30% knew the lowest altitude this illness can occur. There was a correlation between educational background and improved knowledge of altitude illness. Half of the respondents desired further information about AMS, and the Internet was the preferred source of information. CONCLUSIONS: This study suggests that a large population of skiers in North America may be relatively naive to the dangers of AMS. The majority of the respondents were interested in learning more about altitude illness, and the Internet was the most attractive source of information.

An approach to the diagnosis and treatment of plantar fasciitis.

Plantar fasciitis is a painful condition affecting many athletes. Anatomic and biomechanical factors combined with overuse can contribute to its genesis. Correction of gait disturbances, changes in footwear, use of tension night splints, and stretching of tight calf and plantar tissues have all be proven to relieve symptoms. Anti-inflammatory modalities, including medications, iontophoresis, and corticosteroid injection generally provide temporary improvement. Recent studies on the efficacy of extracorporeal shock wave therapy are conflicting. Injections with platelet-rich plasma or sclerotic agents are currently under investigation for use in this and other similar conditions. A small percentage of patients with refractory symptoms may benefit from surgical release of the plantar fascia. Diagnosis and correction of biomechanical factors leading to this condition should be a mainstay of treatment and may prevent recurrences.

Eating disorders among male athletes.

Eating disorders may affect some athletes at rates much greater than the general population. Among male athletes, eating disorders are on the rise. Studies show that males participating in sports in which leanness confers a competitive advantage may be at greater risk of eating disorders. No studies have shown that it is possible to prevent eating disorders in at-risk populations. Once present, eating disorders can be challenging to treat. Psychotherapy and medications have been shown to be helpful. A team approach to the treatment of eating disorders should be used, including regular interaction with a dietician, a mental health professional, a team physician, and other professionals as needed. To maintain participation, athletes must partner with the health care team in their treatment, maintain a healthy weight, and be clear in the understanding that their health is a greater priority than their sport.