Biology subjects

Kalhan, S.

Publications and source records attributed to Kalhan, S..

4 recordsLinked to original sources

bioRxiv2023

People with a tobacco use disorder misattribute non-drug cues as worse predictors of positive outcomes compared to drug cues

Adaptive behaviours depend on dynamically updating internal representations of the world based on the ever-changing environmental contingencies. People with a substance use disorder (pSUD) show maladaptive behaviours with high persistence in drug-taking, despite severe negative consequences. We recently proposed a salience misattribution model for addiction (SMMA; Kalhan et al., (2021)), arguing that pSUD have aberrations in their updating processes where drug cues are misattributed as strong predictors of positive outcomes, but weaker predictors of negative outcomes. We also argue that conversely, non-drug cues are misattributed as weak predictors of positive outcomes, but stronger predictors of negative outcomes. However, these hypotheses need to be empirically tested. Here we used a multi-cue reversal learning task, with reversals in whether drug or non-drug cues are currently relevant in predicting the outcome (monetary win or loss). We show that compared to controls, people with a tobacco use disorder (pTUD), do form misaligned internal representations. We found that pTUD updated less towards learning the drug cues relevance in predicting a loss. Further, when neither drug nor non-drug cue predicted a win, pTUD updated more towards the drug cue being relevant predictors of that win. Our Bayesian belief updating model revealed that pTUD had a low estimated likelihood of non-drug cues being predictors of wins, compared to drug cues, which drove the misaligned updating. Overall, several hypotheses of the SMMA were supported, but not all. Our results implicate that strengthening the non-drug cue association with positive outcomes may help restore the misaligned internal representation in pTUD.

neuroscience↗

bioRxiv2023

Reward prediction-errors weighted by cue salience produces addictive behaviors in simulations, with asymmetrical learning and steeper delay discounting

Dysfunction in learning and motivational systems are thought to contribute to addictive behaviours. Previous models have suggested that dopaminergic roles in learning and motivation could produce addictive behaviours through pharmacological manipulations that provide excess dopaminergic signalling towards these learning and motivational systems. Redish 2004 suggested a role based on dopaminergic signals of value prediction error, while Zhang et al. 2009 suggested a role based on dopaminergic signals of motivation. Both these models present significant limitations. They do not explain the reduced sensitivity to drug-related costs/negative consequences, the increased impulsivity generally found in people with a substance use disorder, craving behaviours, and non-pharmacological dependence, all of which are key hallmarks of addictive behaviours. Here, we propose a novel mathematical definition of salience, that combines aspects of dopamines role in both, learning and motivation, within the reinforcement learning framework. Using a single parameter regime, we simulated addictive behaviours that the Zhang et al. 2009 and Redish 2004 models also produce but we went further in simulating the downweighting of drug-related negative prediction-errors, steeper delay discounting of drug rewards, craving behaviours and aspects of behavioural/non-pharmacological addictions. The current salience model builds on our recently proposed conceptual theory that salience modulates internal representation updating and may contribute to addictive behaviours by producing misaligned internal representations (Kalhan et al., 2021). Critically, our current mathematical model of salience argues that the seemingly disparate learning and motivational aspects of dopaminergic functioning may interact through a salience mechanism that modulates internal representation updating.

neuroscience↗

bioRxiv2021

People with nicotine dependence use-disorder exhibit more prefrontal activity during preparatory control but reduced anterior cingulate activity during reactive control

Reduced inhibitory control and a hypersensitivity to reward are key deficits in drug-dependents, however, they tend to be studied in isolation. Here we seek to understand the neural processes underlying control over reward and how this is different in people with a nicotine use disorder (pNUD). A novel variant of the monetary incentive delay task was performed by pNUD (n = 20) and non-smokers (n = 20), where we added a stop-signal component such that participants had to inhibit prepotent responses to earn a larger monetary reward. Brain activity was recorded using functional magnetic resonance imaging (fMRI). We estimated stop signal reaction times (SSRT), an indicator of impulsivity, and correlated these with brain activity. Inhibitory accuracy scores did not differ between the control group and pNUD. However, pNUD had slower SSRTs, suggesting that they may find it harder to inhibit responses. Brain data revealed that pNUD had greater preparatory control activity in the middle frontal gyrus and inferior frontal gyrus prior to successful inhibitions over reward. In contrast, non-smokers had greater reactive control associated with more activity in the anterior cingulate cortex during these successful inhibitions. SSRT-brain activity correlations revealed that pNUD engaged more control related prefrontal brain regions when SSRTs are slower. Overall, whilst the inhibition accuracy scores were similar between groups, differential neural processes and strategies were used to successfully inhibit a prepotent response. The findings suggest that increasing preparatory control in pNUD may be one possible treatment target in order to increase inhibitory control over reward.

neuroscience↗

bioRxiv2021

Neural and computational processes of accelerated perceptual awareness and decisions: A 7T fMRI Study

Rapidly detecting salient information in our environments is critical for survival. Visual processing in subcortical areas like the pulvinar and amygdala have been shown to facilitate unconscious processing of salient stimuli. It is unknown, however, if and how these areas might interact with cortical networks to facilitate faster conscious perception of salient stimuli. Here we investigated these neural processes using 7T functional Magnetic Resonance Imaging (fMRI) in concert with computational modelling while participants (n = 32) engaged in a breaking continuous flash suppression paradigm (bCFS) in which fearful and neutral faces are initially suppressed from conscious perception but then eventually "breakthrough" into awareness. We found that participants reported faster breakthrough times for fearful faces compared to neutral faces. Drift-diffusion modelling suggested that perceptual evidence was accumulated at a faster rate for fearful faces compared to neutral faces. For both neutral and fearful faces, faster response times coincided with greater activity in the amygdala (specifically within its subregions, including superficial, basolateral and amygdalo-striatal transition area) and the insula. Faster rates of evidence accumulation coincided with greater activity in frontoparietal regions and the occipital lobe, as well as the amygdala. Overall, our findings suggest that hastened perceptual awareness of salient stimuli recruits the amygdala and, more specifically, is driven by accelerated evidence accumulation in fronto-parietal and visual areas. In sum, we have uncovered and mapped distinct neural computations that accelerate perceptual awareness of visually suppressed faces.

neuroscience↗