The Interplay Between Reward-Relevant Life Events and Trait Reward Sensitivity in Neural Responses to Reward Cues

The reward-hypersensitivity model posits that trait reward hypersensitivity should elicit hyper/hypo-approach motivation following exposure to recent life events that activate (goal striving and goal attainment) or deactivate (goal failure) the reward system, respectively. To test these hypotheses, we had 87 young adults with high trait reward (HRew) sensitivity or moderate trait reward (MRew) sensitivity report frequency of life events via the Life Event Interview. Brain activation was assessed during the functional MRI monetary-incentive-delay task. Greater exposure to goal-striving events was associated with higher nucleus accumbens (NAc) reward anticipation among HRew participants and lower orbitofrontal cortex (OFC) reward anticipation among MRew participants. Greater exposure to goal-failure events was associated with higher NAc and OFC reward anticipation only among HRew participants. This study demonstrated different neural reward anticipation (but not outcome) following reward-relevant events for HRew individuals compared with MRew individuals. Trait reward sensitivity and reward-relevant life events may jointly modulate reward-related brain function, which has implications for understanding psychopathology.

Effects of comorbid disorders on reward processing and connectivity in adults with ADHD

ADHD is a neurodevelopmental disorder with a long trajectory into adulthood where it is often comorbid with depression, substance use disorder (SUD) or obesity. Previous studies described a dysregulated dopaminergic system, reflected by abnormal reward processing, both in ADHD as well as in depression, SUD or obesity. No study so far however tested systematically whether pathologies in the brain’s reward system explain the frequent comorbidity in adult ADHD. To test this, we acquired MRI scans from 137 participants probing the reward system by a monetary incentive delay task (MIDT) as well as assessing resting-state connectivity with ventral striatum as a seed mask. No differences were found between comorbid disorders, but a significant linear effect pointed toward less left intrastriatal connectivity in patients depending on the number of comorbidities. This points towards a neurobiologically impaired reward- and decision-making ability in patients with more comorbid disorders. This suggests that less intrastriatal connectivity parallels disorder severity but not disorder specificity, while MIDT abnormalities seem mainly to be driven by ADHD.

Sex Moderates Reward- and Loss-Related Neural Correlates of Triarchic-Model Traits and Antisocial Behavior

Abnormalities in responses to reward and loss are implicated in the etiology of antisocial behavior and psychopathic traits. Although there is evidence for sex differences in neural response to reward and loss, it remains unclear how sex differences may moderate links between these neural responses and the phenotypic expression of antisocial behavior and psychopathic traits. This study examined sex differences in associations of neural response to reward and loss with antisocial personality symptoms and psychopathic traits. Functional neuroimaging data were collected during a monetary incentive delay task from 158 participants. Among males, during loss anticipation, activation in the left nucleus accumbens was negatively associated with antisocial behavior. Among females, during loss feedback, activation in the left nucleus accumbens and left amygdala was negatively associated with antisocial behavior. These results suggest that phenotypic sex differences in psychopathic traits and antisocial behavior may in part be attributable to different etiological pathways.

Comparing adaptive coding of reward in bipolar I disorder and schizophrenia

Background: Deficits in neural processing of reward have been described in both bipolar disorder (BD) and schizophrenia (SZ), but it remains unclear to what extent these deficits are caused by similar mechanisms. Efficient reward processing relies on adaptive coding which allows representing large input spans by limited neuronal encoding ranges. Deficits in adaptive coding of reward have previously been observed across the SZ spectrum and correlated with total symptom severity. In the present work we sought to establish whether adaptive coding is similarly affected in patients with BD. Methods: 25 patients with BD, 27 patients with SZ and 25 healthy controls performed a variant of the Monetary Incentive Delay task during functional magnetic resonance imaging in two reward range conditions. Results: Adaptive coding was impaired in BD and SZ in the posterior part of the right caudate. In contrast, BD did not show impaired adaptive coding in the anterior caudate and right precentral gyrus/insula, where SZ showed deficits compared to healthy controls. Conclusions: BD patients show adaptive coding deficits, that are similar to those observed in SZ in the right posterior caudate. Adaptive coding in BD appeared more preserved as compared to SZ participants especially in the more anterior part of the right caudate and to a lesser extent also in the right precentral gyrus. Thus, dysfunctional adaptive coding could constitute a fundamental deficit in severe mental illnesses that extends beyond the schizophrenia spectrum.

Altered Neural Processing of Reward and Punishment in Women With Methamphetamine Use Disorder

It has been suggested that the altered function of reward and punishment is an important vulnerability factor leading to the development of drug use disorders. Previous studies have identified evidence of neurophysiological dysfunction in the reward process of individuals with substance use disorders. To date, only a few event-related potential (ERP) studies have examined the neural basis of reward and punishment processing in women with methamphetamine (MA) use disorders. The current ERP research aims to investigate the neurophysiological mechanisms of reward and punishment in women with MA use disorder using a monetary incentive delay task. Nineteen women with MA use disorder (MA group) and 20 healthy controls (HC group) were recruited in this study. The behavioral data showed that the reaction time (RT) was faster and the response accuracy (ACC) was higher for the potential reward and punishment conditions compared to neutral conditions. During the monetary incentive anticipation stage, the Cue-P3, and stimulus-preceding negativity (SPN) were larger in the MA group than in the HC group. The SPN under the potential reward condition was larger than that under the neutral condition in the MA group but not in the HC group. During the monetary incentive consummation stage, the feedback-related negativity and feedback P3 (FB-P3) following positive feedback were significantly larger than negative feedback in the potential reward condition for the HC group, but not for the MA group. However, the FB-P3 following negative feedback was significantly larger than positive feedback in the potential punishment condition for the MA group, but not the HC group. The results suggest that women with MUD have stronger expectations of generic reward and stronger response of generic harm avoidance, which could be targeted in designing interventions for women with MA use disorder.

Reward disturbances in antipsychotic-naïve patients with first-episode psychosis and their association to glutamate levels

Background Aberrant anticipation of motivational salient events and processing of outcome evaluation in striatal and prefrontal regions have been suggested to underlie psychosis. Altered glutamate levels have likewise been linked to schizophrenia. Glutamatergic abnormalities may affect the processing of motivational salience and outcome evaluation. It remains unresolved, whether glutamatergic dysfunction is associated with the coding of motivational salience and outcome evaluation in antipsychotic-naïve patients with first-episode psychosis. Methods Fifty-one antipsychotic-naïve patients with first-episode psychosis (22 ± 5.2 years, female/male: 31/20) and 52 healthy controls (HC) matched on age, sex, and parental education underwent functional magnetic resonance imaging and magnetic resonance spectroscopy (3T) in one session. Brain responses to motivational salience and negative outcome evaluation (NOE) were examined using a monetary incentive delay task. Glutamate levels were estimated in the left thalamus and anterior cingulate cortex using LCModel. Results Patients displayed a positive signal change to NOE in the caudate (p = 0.001) and dorsolateral prefrontal cortex (DLPFC; p = 0.003) compared to HC. No group difference was observed in motivational salience or in levels of glutamate. There was a different association between NOE signal in the caudate and DLPFC and thalamic glutamate levels in patients and HC due to a negative correlation in patients (caudate: p = 0.004, DLPFC: p = 0.005) that was not seen in HC. Conclusions Our findings confirm prior findings of abnormal outcome evaluation as a part of the pathophysiology of schizophrenia. The results also suggest a possible link between thalamic glutamate and NOE signaling in patients with first-episode psychosis.

Neuronally-Enriched Exosomal miR-27b Reveals Mechanism for Ibuprofen-Induced Acute Effects on Reward-Related Brain Processing in a Randomized, Placebo-Controlled, Double-Blind Trial

This double-blind, randomized, repeated measures study evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females,10 males) completed a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from plasma and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. Our findings indicate that miR-27b could be an important messaging molecule altered by anti-inflammatory drugs that relates to the processing of positive or negative valenced information.

#3097 Temporal and spectral dynamics of reward and risk processing in the amygdala revealed with stereo-EEG recordings in epilepsy

Objectives/AimsTo examine the temporal and spectral characteristics of local field potentials recorded from the amygdala in epilepsy in the context of the anticipation and receipt of rewards and losses using an incentive learning task and a risky decision-making task.Methods16 Epilepsy patients completed two tasks. In the monetary incentive delay (MID) task, patients saw reward and loss cues which indicated whether money could be won or lost depending on whether a subsequent response was or was not quick/accurate enough, respectively. This was compared with neutral cues where responses were neither rewarded nor punished regardless of response.In the risk task, patients were presented with two face down cards with values ranging from 1 to 10. When the first card is revealed, patients have to choose whether to bet or not bet that the second card is higher. After the card is revealed, patients receive a monetary reward if it is higher and a loss if it is lower. If patients do not bet, they receive nothing.ResultsIn both tasks, patients showed larger left amygdala theta band oscillatory activity to the receipt of monetary rewards compared to no money. In contrast, there were no significant responses to monetary losses. During the decision phase of the risk task, there was increased theta activity when patients chose to bet instead of not betting and when the decision had low risk (card <= 5) compared to high risk (card above 5). There were no effects of uncertainty.ConclusionsThe combined results of these two studies embellish our understanding of the role of the amygdala in motivation and decision-making processes and lend further support for its role in reward related processes rather than its often cited fear-related functions (Baxter & Murray, 2002; Murray, 2007). Theta activation is linked to cognitive processes in frontal cortices and coupled to MTL activity (Helfrich & Knight, 2016). As left amygdala theta activation was only recruited when patients were making their bet and not just anticipating reward, the pattern of results lend support to its role in cognition-emotion interactions specific to risk and reward but not uncertainty. Indeed, the hemispheric asymmetry is highly consistent with EEG studies showing left prefrontal dominance in reward processing (Manssuer et al., 2021).