Biology subjects

Kuzmanovic, B.

Publications and source records attributed to Kuzmanovic, B..

4 recordsLinked to original sources

bioRxiv2026

Metabolic state and energy reserve dynamically shape human decision-making

Animals continuously adapt their behaviour to changing physiological needs through flexible regulation of behavioural control. However, how the energetic state shapes the distinct components of this adaptive control in humans remains poorly understood. Here, we tested how fasting-induced energy deficits and stored energy reserves jointly regulate inhibitory control and incentive motivation in healthy participants. Fasting selectively increased impulsivity for food rewards, an effect attenuated by body fat percentage. In contrast, fasting increased effort expenditure across both food and monetary rewards, revealing a domain-general increase in motivation best explained by relative energy deficit--the ratio of energy expended during fasting to stored energy reserves. Neither effect was explained by changes in subjective reward valuation. Although self-report questionnaires captured stable behavioural tendencies, they failed to account for state-dependent behavioural variation. Together, these findings show that inhibitory control and motivation are governed by distinct metabolic principles operating across different timescales, revealing that adaptive behavioural control depends on the energetic significance of metabolic state rather than on fasting alone.

neuroscience↗

bioRxiv2025

Reduced Model-Based Control in Gambling Disorder Despite Intact Neural Value and Task Structure Representations

Disordered gambling has been linked to impairments in goal-directed (model-based) control and reinforcement learning. Here we investigated the potential neural basis of this impairment using a sequential reinforcement learning task (modified two-step-task), computational modeling, and functional magnetic resonance imaging (fMRI) in individuals exhibiting symptoms of disordered gambling (GD) and matched healthy controls (HC, n=30 per group). Model-agnostic analyses replicated the effects of reduced performance and reduced model-based control in the gambling group, both in terms of choice and response time effects. Computational modeling of choice behavior confirmed that this effect was due to reduced model-based control in the gambling group. Analyses of choices and response times using drift diffusion modeling revealed a more complex pattern, where behavioral impairments in the gambling group were linked to changes across several parameters reflecting drift rate modulation and asymptote, as well as non-decision time. Despite these pronounced behavioral differences, the gambling group exhibited largely intact neural effects related to the task transition structure, reward feedback and trial-to-trial behavioral adjustments. Results are discussed with respect to current neurocomputational models of behavioral dysregulation in disordered gambling.

neuroscience↗

bioRxiv2025

A lateralized pathway for associating nutrients with flavors

Animals learn about the external world, in part, via interoceptive signals1,2. For example, the nutrient content of food is first estimated in the mouth, in the form of flavor, and then measured again via slower signals from the gut. How these signals from the mouth and gut are integrated to drive learning is unknown. Here we identify a lateralized dopamine pathway that is specialized for learning about the nutrient content of food. We show that dopamine neurons in the ventral tegmental area (VTADA) are necessary for associating nutrients with flavors, and that post-ingestive nutrients trigger DA release selectively in a small region of the anterior basolateral amygdala (BLA) but not canonical DA targets in striatum. Remarkably, this nutrient-triggered DA release occurs preferentially on the left side of the brain in both mice and humans, revealing that the DA system is functionally lateralized. We identify the gut sensors that are responsible for nutrient-triggered DA release; show that they activate BLA-projecting DA neurons defined by expression of cholecystokinin (CCK); and demonstrate that stimulation of DA axon terminals in the anterior BLA drives flavor-nutrient learning but not other aspects of feeding behavior. Two-photon imaging of neurons in the left anterior BLA reveals that they integrate gustatory and post-ingestive cues, and silencing these neurons prevents flavor-nutrient learning. These findings establish a neural basis for how animals learn about the nutrient content of their food. They also reveal unexpectedly that post-ingestive nutrients are differentially represented on the right and left sides of the brain.

neuroscience↗

bioRxiv2022

Appetitive cue exposure increases neural reward responses without modulating temporal discounting

When given a choice, humans and many animals prefer smaller but sooner over larger but later rewards, a tendency referred to as temporal discounting. Alterations in devaluation of future rewards have been reported in a range of maladaptive behaviors and clinical conditions. Although temporal discounting is highly stable over time and testing environments (e.g., laboratory vs. virtual reality), it is partly under contextual control. For example, highly appetitive cues such as erotic images might increase preferences for immediate rewards, although overall evidence remains mixed. Dopaminergic circuit activity and striatal dopamine concentrations are often assumed to drive increases in temporal discounting following appetitive cue-exposure, yet this was never explicitly tested. Here we examined cue-reactivity effects (erotic vs. neutral pictures) on subsequent temporal discounting in a pre-registered within-subjects study in healthy male participants (n=38). Functional magnetic resonance imaging (fMRI) assessed neural cue-reactivity, value-computations and choice-related effects. Preregistered analyses replicated previous findings of value coding in ventromedial prefrontal cortices, striatum and cingulate cortex. Likewise, as hypothesized, lateral prefrontal cortex activity increased during choices of delayed rewards, potentially reflecting cognitive control. As predicted, erotic vs. neutral cue exposure was associated with increased activity in attention and reward circuits. Contrary to our preregistered hypotheses, temporal discounting was largely unaffected by cue exposure. Likewise, cue-reactivity in key areas of the dopaminergic reward circuit (Nacc, VTA) was not significantly associated with changes in behavior. Our results indicate that behavioral effects of erotic cue exposure on temporal discounting might not be as unequivocal as previously thought and raise doubt on the hypothesis of an upregulated dopaminergic ramping mechanism, that might support myopic approach behavior towards immediate rewards.

neuroscience↗