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Versace, F.

Publications and source records attributed to Versace, F..

11 recordsLinked to original sources

What a stimulus predicts, not what it depicts, determines striatal reward signals

Free viewing of emotional pictures activates motivational circuits as a function of arousal and valence, yet, because no real outcomes are delivered, anticipatory wanting and consummatory liking cannot be dissociated. Gustatory neuroimaging paradigms deliver actual rewards but use impoverished, affectively neutral cues that do not engage natural selective attention. We bridged these paradigms by presenting emotional images alongside food photographs that either predicted juice delivery (Food+) or did not (Food-), all within a single fMRI session. On each Food+ trial, participants indicated in real time whether they wanted the juice, enabling a within-subject dissociation of anticipatory from consummatory signals. Nucleus accumbens showed a large and selective response to Food+ cues that exceeded activation to both pleasant (erotica) and unpleasant (mutilation) high-arousal images, establishing that mesolimbic engagement tracked outcome prediction rather than emotional arousal, affective valence, or visual content. A temporal dissociation further revealed that nucleus accumbens carried the dominant anticipatory signal during the cue period, while ventromedial prefrontal cortex carried the dominant outcome-period signal at juice delivery, a pattern consistent with the wanting and liking distinction. Representational similarity analysis confirmed that outcome prediction, rather than emotional arousal, affective valence, or visual category, was the dominant organizing principle of the multivariate neural response across the full region-of-interest network. Together, these findings show that whether a visual stimulus engages reward circuitry depends less on what it depicts than on what it predicts, and provide a framework for studying individual differences in appetitive motivation and cue-induced eating. Significance statementWhether a food image engages brain reward circuitry depends not on what it depicts, but on what it predicts. We scanned participants while they viewed food images that either preceded a real opportunity to receive juice or did not, alongside erotic, threatening, and neutral scenes. Nucleus accumbens, a core reward region, responded selectively to food images predicting juice, with a response that exceeded even the response to erotic images. Ventromedial-prefrontal cortex, by contrast, tracked actual juice receipt, dissociating anticipation from consumption. Across a ten-region network, learned reward prediction, rather than emotional arousal, valence, or visual category, organized the neural response. These findings establish a human neuroimaging paradigm for studying how cue-driven motivation goes awry in obesity, addiction, and compulsive eating.

neuroscience↗

Emotion regulation or dual task? Dissociation of neural and behavioral measures

Cognitive reappraisal, the deliberate reinterpretation of emotional events, is widely considered an effective emotion regulation strategy, and modulation of the late positive potential (LPP) during negative affect reduction has become the primary electrophysiological evidence for volitional emotional control. Experimental instructions, however, impose dual-task demands that free viewing does not, confounding reappraisal with cognitive load. By including instructions to increase emotional responses to pictures ("enhance") as well as instructions to decrease ("suppress"), different predictions are generated. If the LPP reflects regulation, then, compared to free viewing, suppress instructions should decrease LPP amplitude, and enhance instructions should increase LPP amplitude. If modulation instead reflects cognitive load, both instructions should reduce the LPP, as both impose an additional cognitive task. In a sample of 107 participants, evaluative ratings confirmed that regulation instructions modulated reported emotional intensity in the expected directions (Enhance > View > Suppress), but that both enhance and suppress instructions reduced LPP amplitude compared to free viewing, with Bayesian model comparisons providing strong evidence against direction-specific regulation and in favor of cognitive load. Whole-scalp multivariate pattern analysis confirmed that no instruction-related neural signal exists at any scalp location or latency within the first second after stimulus onset. These data indicate that LPP modulation following both instruction types reflects dual-task cognitive load rather than volitional emotional control. Significance StatementCognitive reappraisal is considered the gold standard of emotion regulation, and reduced late positive potential (LPP) amplitude during negative emotion suppression is the primary neural evidence that humans can voluntarily control emotional responses. The current data are inconsistent with this regulatory account and instead support a cognitive load interpretation. Whether instructed to enhance or suppress emotional responses, LPP amplitude was reduced in both conditions relative to free viewing, consistent with attentional resource competition rather than directional regulatory control. The same participants reported successfully regulating emotional experience in opposite directions, producing a clear dissociation between neural and behavioral measures. These findings challenge a basic tenet of emotional regulation and raise questions concerning LPP modulation as a biomarker of regulatory capacity.

neuroscience↗

Human prostaglandin reductases dearomatize and inactivate benzothiazinone antitubercular drugs

Macozinone (MCZ, PBTZ169) is a potent clinical stage benzothiazinone antitubercular agent that covalently inhibits the essential mycobacterial flavoenzyme DprE1. In some mammals, MCZ undergoes reductive dearomatization to H2MCZ, a Hydride Meisenheimer Complex, identified as the major circulating metabolite in humans. We demonstrate for the first time that the NADPH-dependent human prostaglandin reductases PTGR1 and PTGR2 catalyze MCZ dearomatization into H2MCZ, resulting in loss of antimycobacterial activity. This reaction represents a heretofore undescribed host-mediated metabolic inactivation pathway for a therapeutic agent. Although H2MCZ may constitute a transient reactive intermediate, ex vivo and cellular data indicate that it does not contribute to DprE1 inhibition in vivo. Pharmacological inhibition of PTGR1 and PTGR2 using diclofenac, indomethacin, dicumarol, or the selective inhibitor PTGR2-IN-1 suppresses H2MCZ formation and partially restores MCZ antimycobacterial activity in vitro. Together, our findings uncover a previously unrecognized noncanonical enzymatic mechanism of drug metabolism involving dearomatization in humans. Targeting prostaglandin reductases may represent a strategy to enhance benzothiazinone exposure and efficacy.

pharmacology and toxicology↗

Do GLP-1 Receptor Agonists Alter Brain Responses to Reward-Related Cues? A Systematic Review

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved for treating type 2 diabetes and obesity and are under investigation as potential treatments for substance use disorders (SUD). GLP-1 RA-induced weight loss is thought to arise from both peripheral effects on gastrointestinal function and central modulation of appetite and reward circuits, though the exact mechanisms are unclear. Functional magnetic resonance imaging (fMRI) studies examining brain responses to reward-related cues can help clarify the central mechanisms through which GLP-1 RAs influence reward-seeking behavior. We systematically reviewed the fMRI literature examining how GLP-1 RAs affect brain responses to reward-related cues. We identified 1,209 records through a comprehensive literature search. After screening, only 11 studies met eligibility criteria. The vast majority assessed reactivity to food-related cues, with only one examining drug-related cues (alcohol), leaving neural mechanisms relevant to SUD largely unexplored. None included non-food emotional stimuli as control conditions. Several methodological limitations emerged. Most studies enrolled 20 or fewer participants per group, limiting statistical power. Treatment protocols varied substantially, with some assessing cue responses after single-dose administration and others after chronic treatment. Heterogeneity in medications used further confounds interpretation. The limited evidence tentatively suggests that acute GLP-1 RA administration may reduce brain reactivity to food cues in appetite and reward regions. However, effects appear inconsistent and may attenuate over time. Future studies should recruit larger samples, standardize agents and dosing, and assess responses to diverse motivationally relevant stimuli.

neuroscience↗

Profiles of Neuroaffective Responding to Natural Reward-Predicting Cues and Alcohol Images in Alcohol Use Disorder: An Event-Related Potential Approach

BACKGROUND AND AIMSIncentive salience attribution (ISA) is the process by which the cues associated with reward take on value themselves. Individual differences in ISA are known to predict reward seeking and consuming behavior in animals and humans, suggesting prognostic potential in use disorders like alcohol use disorder (AUD). Since AUD etiology is thought to involve changes in natural (e.g., food) reward processing as much as alcohol-related processing, current research tested if differences in natural reward cue ISA are apparent, and predictive of behavior, in AUD. METHODS30 individuals meeting AUD criteria and reporting heavy alcohol consumption on timeline follow-back (TLFB) participated. Subjects completed a validated ISA task wherein pictures depicting inherently appetitive, aversive, or emotionally neutral content are shown along with pictures that are less evocative but are predictive of reward (candy) delivery and (in this study) also alcohol images. To capture individual variations in ISA, a picture-elicited neural response that scales with picture salience - the late positive potential (LPP) - is indexed and then submitted to k-means clustering to classify different modulation profiles. RESULTSReplicating prior work, clustering indicated a 2-group solution where an "F>P" (n=14) group showed enhanced LPPs for food-predicting, relative to standard appetitive, pictures and an "F P versus F P and F<P groups. CONCLUSIONSSimilarly sized groups of individuals who were more versus less responsive to natural reward cues is consistent with prior studies in non-AUD samples. At the same time, the lack of commensurate differences in task reward consumption differs from those studies, and could reflect change in natural reward processing in individuals with AUD. Implications for continued research are discussed.

neuroscience↗

Electrophysiological normative responses to emotional, neutral, and cigarette-related images.

To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. Yet, to investigate psychophysiological emotional responses, it might be more appropriate to select pictures using normative neurophysiological responses rather than normative subjective ratings. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of pleasure and emotional arousal were collected from 763 individuals (52% females, 41% white) aged between 18 and 65 (mean = 43). For each image, the mean amplitude of the late positive potential (LPP, an electrophysiological index of motivational relevance) and the mean subjective ratings of valence and arousal were calculated. We validated our procedure by showing that the subjective ratings of valence and arousal from this sample were highly correlated to the IAPS published norms (Pearson r=.97 for pleasure and r=.82 for emotional arousal). LPP responses and subjective ratings of emotional arousal also were correlated (Pearson r = .61), but some categories that participants reported being significantly more arousing than neutral (i.e., food, landscapes, and unpleasant objects) did not evoke LPPs significantly different from those evoked by neutral pictures. Researchers interested in probing the brains affective systems can use these electrophysiological normative responses to create emotional probes that evoke reliable neuroaffective responses.

neuroscience↗

Individual differences in late positive potential amplitude and theta power predict cue-induced eating

Both the brains affective and cognitive systems are known to regulate cue-induced behaviors. Although it is established that individual differences in affective processing of food-related cues predict cue-induced eating, we have yet to investigate how both affective and cognitive mechanisms act in tandem to regulate cue-induced eating. We recorded electroencephalogram (EEG) from 59 adults while they viewed emotional & food-related images that preceded the delivery of food rewards (candies) or nonfood objects (beads). We measured the amplitude of the late positive potential (LPP) in response to images and power in the theta (4-8 Hz) frequency band after the candy or bead was dispensed to the participant. We found that individuals with larger LPP responses to food cues than to pleasant images (C>P group) ate significantly more during the experiment than did those with the opposite response pattern (P>C group, p < 0.001). Furthermore, we found that individuals with higher theta power after dispensation of the candy than of the bead ({theta}CA>{theta}BE) ate significantly more than did those with the opposite response pattern ({theta}BE>{theta}CA, p < 0.001). Finally, we found that the crossed P>C and {theta}BE>{theta}CA group ate less (p < 0.001) than did the other three groups formed by crossing the LPP and theta group assignments, who exhibited similar eating behavior on average (p = 0.662). These findings demonstrate that motivational salience and cognitive control converge to independently confer vulnerability or resilience to cue-induced behaviors, underscoring the need for individualized treatments to mitigate maladaptive behaviors. HIGHLIGHTSO_LILPP responses to motivationally salient stimuli predict cue-induced eating. C_LIO_LITheta power in the presence of food rewards predicts cue-induced eating. C_LIO_LIThe LPP & theta may inform the development of personalized weight-loss interventions. C_LI

neuroscience↗

Neuroaffective profiles are associated with e-cigarette use

IntroductionIdentifying the psychophysiological underpinnings of cue-induced compulsive nicotine use will provide new targets for relapse prevention treatments. We tested whether neuroaffective responses to motivationally relevant stimuli are associated with cue-induced nicotine self-administration. We hypothesized that smokers with stronger neuroaffective responses to nicotine-related cues than to pleasant stimuli (C>P) are more vulnerable to cue-induced nicotine self-administration than smokers with stronger neuroaffective responses to pleasant stimuli than to nicotine-related cues (P>C). MethodsSmokers (N=36) looked at pleasant, unpleasant, neutral, and nicotine-related images signaling that an electronic nicotine delivery system (ENDS) was immediately available for use. We measured event-related potentials (a direct measure of cortical activity) and computed the amplitude of the late positive potential, a robust index of motivational salience. We used k-means cluster analysis to identify individuals characterized by the C>P or the P>C neuroaffective profile. We compared the ENDS use frequency in the two groups using quantile regression for counts. ResultsCluster analysis assigned 18 smokers to the C>P profile and 18 smokers to the P>C profile. Smokers with the C>P neuroaffective profile used the ENDS significantly more often than smokers with the P>C profile. Significant differences in the number of puffs persisted across different quantiles. ConclusionsThese results support the hypothesis that individual differences in the tendency to attribute motivational salience to drug-related cues underlie vulnerability to cue-induced drug self-administration. ImplicationsBy linking brain reactivity profiles to nicotine self-administration, we identified a neuroaffective biomarker that could guide the development of personalized treatments to prevent smoking relapse.

neuroscience↗

Estimating statistical power for event-related potential studies using the late positive potential

The late positive potential (LPP) is a common measurement used to study emotional processes of subjects in event-related potential (ERP) paradigms. Despite its extensive use in affective neuroscience, there is presently no gold standard for how to appropriately power ERP studies using the LPP in within-subject and between-subjects experimental designs. The present study investigates how the number of trials, number of subjects, and magnitude of the effect size affect statistical power in analyses of the LPP. Using Monte Carlo simulations of ERP experiments with varying numbers of trials, subjects, and effect sizes, we measured the probability of obtaining a statistically significant effect in 1,489 different experiments repeated 1,000 times each. Predictably, our results showed that statistical power increases with increasing numbers of trials and subjects and at larger effect sizes. In addition, we found that higher levels of statistical power can be achieved with lower numbers of subjects and trials and at lower effect sizes in within-subject than in between-subjects designs. Furthermore, we found that, as subjects are added to an experiment, the slope of the relationship between effect size and statistical power increases and shifts to the left until the power asymptotes to nearly 100% at higher effect sizes. This suggests that adding more subjects greatly increases statistical power at lower effect sizes (<1 {micro}V) compared with more robust (>1.5 {micro}V) effect sizes.

neuroscience↗

A Neurophysiological Measure of Reward Sensitivity and its Limited Association with Anhedonia in Adolescents and Young Adults

Anhedonia (i.e., the attenuated ability to enjoy pleasurable stimuli) characterizes multiple mood disorders, but its neurophysiological underpinnings are not yet clear. Here, we measured event-related potentials in 116 adolescents and young adults engaged in a signal detection task designed to objectively characterize the anhedonic phenotype. In line with previous studies, the behavioral results showed that approximately 35% of the sample did not develop a response bias towards the more frequently rewarded stimuli (a sign of low hedonic capacity). The event-related potentials (ERPs) evoked by the reward feedback stimuli delivered during the task showed that individuals that did not develop a response bias had significantly less cortical positivity at Fz from 224 ms to 316 ms post feedback onset compared to those that developed a response bias during the task. However, further analyses showed that this between groups difference was relatively weak, as it disappeared when we controlled for response-locked ERPs. Furthermore, the response bias observed in the signal detection task was not strongly associated with self-reported ratings of hedonic capacity. We conclude that even though the signal detection task may be used as a reward sensitivity measure in neurotypical adolescents and young adults, this task may only be able to detect clinically significant levels of anhedonia in this particular population.

neuroscience↗

The reality of "food porn": Larger brain responses to food-related cues than to erotic images predict cue-induced eating.

While some individuals can defy the lure of temptation, many others find appetizing food irresistible. Using event-related potentials, we showed that individuals who find food-related images more motivationally relevant than erotic ones (\"sign-trackers\") are more susceptible to cue-induced eating and, in the presence of a palatable food option, eat twice as much as individuals with the opposite brain reactivity profile (\"goal-trackers\"). These findings contribute to the understanding of the neurobiological basis of vulnerability to cue-induced behaviors.

neuroscience↗