Pavlovian conditioning holds the potential to incentivize environmental cues, leading to approach behavior toward them, even outside our awareness. Animal models suggest that this is particularly true for the so-called sign-tracker (ST) phenotype, which is considered to reflect a predisposition toward developing addiction-related behaviours. Despite its potential clinical relevance, few studies have demonstrated the translational validity of this model, likely due to difficulties in studying Pavlovian processes in humans. To fill this gap, we combined an ecological momentary assessment with ambulatory peripheral autonomic monitoring to test the hypothesis that traits associated with ST in preclinical studies would be associated with attribution of high incentive salience to reward-related cues. Several times for 2 days, participants were asked to rate the attractiveness of several preselected ecological rewards (e.g., coffee) and the preceding cues (the smell of coffee) while their electrocardiogram was recorded. While no absolute difference in subjective and physiological measures of motivational approach to daily cues compared with rewards emerged, individuals with high levels of impulsivity, obsessive-compulsive, and addiction-prone behaviors rated as more attractive and showed a greater increase in sympathetic arousal to cues versus rewards. The opposite pattern emerged for those with low levels in those dispositional traits, who responded more (both subjectively and physiologically) to rewards compared with their preceding cues. This study represents an attempt to answer the call to parcel complex behaviors into smaller constructs, improving the early detection of those who are vulnerable to develop psychopathological disorders, particularly in the domain of impulse control such as addiction.

The “Sign-tracker/Goal-tracker” (ST/GT) is an animal model of individual differences in learning and motivational processes attributable to distinctive conditioned responses to environmental cues. While GT rats value the reward-predictive cue as a mere predictor, ST rats attribute it with incentive salience, engaging in aberrant reward-seeking behaviors that mirror those of impulse control disorders. Given its potential clinical value, the present study aimed to map such model onto humans and investigated resting state functional magnetic resonance imaging correlates of individuals categorized as more disposed to sign-tracking or goal-tracking behavior. To do so, eye-tracking was used during a translationally informed Pavlovian paradigm to classify humans as STs (n = 36) GTs (n = 35) or as Intermediates (n = 33), depending on their eye-gaze towards the reward-predictive cue or the reward location. Using connectivity and network-based approach, measures of resting state functional connectivity and centrality (role of a node as a hub) replicated preclinical findings, suggesting a major involvement of subcortical areas in STs, and dominant cortical involvement in GTs. Overall, the study strengthens the translational value of the ST/GT model, with important implications for the early identification of vulnerable phenotypes for psychopathological conditions such as substance use disorder.

Perseverative cognition (PC) is a transdiagnostic risk factor that characterizes both hypo-motivational (e.g., depression) and hyper-motivational (e.g., addiction) disorders; however, it has been almost exclusively studied within the context of the negative valence systems. The present study aimed to fill this gap by combining laboratory-based, computational and ecological assessments. Healthy individuals performed the Probabilistic Reward Task (PRT) before and after the induction of PC or a waiting period. Computational modeling was applied to dissociate the effects of PC on reward sensitivity and learning rate. Afterwards, participants underwent a one-week ecological momentary assessment of daily PC occurrence, as well as anticipatory and consummatory reward-related behavior. Induction of PC led to increased response bias on the PRT compared to waiting, likely due to an increase in learning rate but not in reward sensitivity, as suggested by computational modeling. In daily-life, PC increased the discrepancy between expected and obtained rewards (i.e., prediction error). Current converging experimental and ecological evidence suggests that PC is associated with abnormalities in the functionality of positive valence systems. Given the role of PC in the prediction, maintenance, and recurrence of psychopathology, it would be clinically valuable to extend research on this topic beyond the negative valence systems.

Background: Anhedonia and rumination, a form of repetitive negative thinking (RNT), are key features of depression associated with poor treatment outcomes, chronic disease progression, and an increased risk of suicidality. Although their interaction is thought to sustain depressive states, the state-level mechanisms linking these symptoms remain poorly understood. Methods: In this multilevel, randomized within-subjects study, 62 individuals (n = 38 females) with varying levels of depressive symptoms completed the Probabilistic Reward Task (PRT) under two conditions: experimentally induced RNT and an active control. Concurrent electroencephalography was employed to assess electroencephalographic markers of reward functioning. Results: RNT significantly attenuated both reward response bias and feedback-related positivity (FRP) amplitudes, with the most pronounced effects in individuals with more severe depressive symptoms. These effects were not attributable to differences in task difficulty or perceptual cortical processing of PRT stimuli, supporting the specificity of RNT’s impact on reward-related processes. Conclusions: RNT may transiently disrupt behavioral and neural indicators of reward functioning. These findings suggest that cognitive states such as RNT can exacerbate or reveal the latent reward-processing deficits typically observed in individuals with anhedonia. This state-dependent sensitivity highlights the potential utility of targeting RNT to restore reward processing in depression.

Purpose: To evaluate the long-term efficacy of vagus nerve stimulation (VNS) in reducing tonic-clonic seizures (TCS), drop attacks, and seizure clusters in adults with drug-resistant epilepsy (DRE). Methods: This retrospective, single-center study included adults with DRE who received VNS and had ≥ 12 months of follow-up. Data were collected pre-implantation (T0), at 12 months (T1), and last follow-up (T2). Outcomes included reduction in total seizure frequency and severity, frequency of TCS and drop attacks, and frequency/duration of seizure clusters. Battery replacement and tolerability were also assessed. Results: Eighty-seven subjects (51 males, median age 33 at T0) with a mean follow-up of 8 years were analyzed. At T2, 54% showed reduced total seizure frequency and 71% reported decreased severity/duration. Among those with baseline TCS, 75% (T1)–80.6% (T2) had frequency reduction, with 20.6% seizure-free at T2. Drop attacks improved in > 70% of cases, with resolution in 21.8% at T2. Over 80% with seizure clusters reported decreased frequency/duration at both T1 and T2. Response rates for specific seizure types significantly exceeded non-response ( p < 0.001). Battery replacement was required in 85.7% near depletion. Side effects occurred in 49.4%, mostly mild/transient; major complications were rare. Conclusion: VNS exerts a robust effect on the most disabling seizures—TCS, drop attacks, and seizure clusters—surpassing its impact on overall seizure burden. Benefits appear within the first year and persist long term. These findings support a more tailored approach to VNS candidate selection, advocating earlier use in patients with refractory, harmful seizures not eligible for curative surgery.

Anhedonia and rumination, a form of repetitive negative thinking (RNT), are key features of depression associated with poor treatment outcomes, chronic disease progression, and an increased risk of suicidality. Despite their hypothesized interaction in sustaining depression, the mechanisms connecting these symptoms remain unclear. This within-subjects study examined reward processing during the Probabilistic Reward Task (PRT) under experimentally induced RNT and an active control condition in 62 individuals (n = 38 females) with varying levels of depressive symptoms. Results indicated a significantly reduced reward response bias and feedback-related positivity (FRP) during the RNT condition, with effects most pronounced in individuals with severe depressive symptoms. Additionally, FRP amplitude was correlated with both reward response bias and subjective response to the induction. These findings suggest that RNT worsens both behavioral and electrophysiological markers of reward processing deficits in individuals with high depressive symptoms, offering insight into the mechanisms linking rumination and anhedonia in depression.