Towards a Neurobehavioral Phenotype of Human Hedonic Capacity

770 

Abstract Submission 

Ryan Yan¹, Leili Mortazavi¹, Brian Knutson², Hongye Li³

¹Stanford University, Stanford, CA, ²Stanford University, Palto Alto, CA, ³University of California, Los Angeles, Los Angeles, CA

Ryan Yan  
Stanford University
Stanford, CA

Leili Mortazavi  
Stanford University
Stanford, CA

Brian Knutson, PhD  
Stanford University
Palto Alto, CA

Hongye Li  
University of California, Los Angeles
Los Angeles, CA

Hedonic capacity, or the ability to experience pleasure, has been identified as an important mental health symptom profile (Cuthbert & Insel, 2013; Insel et al., 2010). Reduced hedonic capacity is a key symptom in various psychiatric disorders including depression and schizophrenia. Neuroimaging studies have linked self-reported hedonic capacity to reduced subcortical activity (especially in the ventral striatum) during reward processing, particularly during reward anticipation (Green et al., 2019; Wacker et al., 2009; Wu et al., 2014). Many of these studies, however, were conducted on depressed patients. Additionally, research has not clarified whether blunted ventral striatal responses to reward are specifically associated with self-reported reward anticipation versus consumption.

In a pre-registered study, we will recruit 60 healthy participants in total. This abstract presents preliminary results based on N = 41 quality-assured participants collected to date. Participants completed two reward processing tasks while being scanned with functional Magnetic Resonance Imaging (fMRI at 3T GE, TE = 25 ms, TR = 2000 ms, flip = 70°, 28 slices) – the Monetary Incentive Delay (MID) task (Knutson et al., 2001), and a skewed gambling task (Wu et al., 2011). In MID task trials, participants see a cue indicating potential monetary gain or loss ($5, $1 or $0 gain or loss), then responded to a rapidly presented target after waiting a variable delay, to try to acquire gains or avoid losses. In skewed gambling task trials (Leong et al., 2016), participants saw a risky option and a safe option, chose between them, and were notified of the outcome. Thus, both tasks included anticipation phase and outcome phases.
High resolution images (1.5 mm isotropic) were acquired with manually-prescribed partial coverage of mesolimbic projections spanning the midbrain and the dorsal striatum. Self-reported hedonic capacity was measured by the Temporal Experience of Pleasure Scale (TEPS), which contains an anticipatory component (TEPS-ANT) and a consummatory component (TEPS-CON). Functional neuroimaging data was preprocessed using a standard protocol with AFNI (Srirangarajan et al., 2021) and co-registered to MNI space using FSL. The time course data and regression coefficients for anticipation and outcome periods were extracted for mesolimbic projection regions (including the Nucleus Accumbens (NAcc) of the ventral striatum).

Healthy participants with higher hedonic capacity (as indexed by a higher TEPS score) tended to respond faster to obtain monetary rewards (β = -0.27, p = .055). This pattern appeared to generalize over all cue types, not just the high reward incentive responses. Averaged peak NAcc signal during high reward (+$5) anticipation was also associated with higher TEPS-ANT (β = 0.31, p = .045), but not with TEPS-CON (β = 0.03, p = .839). This association of TEPS-ANT with neural activity was specific to the +$5 anticipatory activity, since neither NAcc nor MPFC response to +$5 outcome was associated with the TEPS score.
Further, observed results trended towards generalizing to the skewed gambling task.
While +$5 cue anticipatory NAcc activity in the MID task was not significantly associated with NAcc activity during anticipation of gamble acceptance (β = 0.15, p = .169), NAcc activity in anticipation of gamble outcomes was indeed associated with overall TEPS score (β = 0.32, p = .036). Unlike the MID task, this association was not specific to TEPS-ANT (β = 0.20, p = .198).

In a preliminary analysis, self-reported variation in hedonic capacity was associated with NAcc activity during reward anticipation in healthy humans. This association may generalize to another incentivized task with an anticipatory phase. These preliminary findings are consistent with the idea that hedonic capacity is an affective trait which can vary across healthy and clinical samples.

Psychiatric (eg. Depression, Anxiety, Schizophrenia)

Reward and Punishment ¹

Activation (eg. BOLD task-fMRI) ²

Subcortical Structures

BOLD fMRI

Affective Disorders

Basal Ganglia

Data analysis

Dopamine

Emotions

FUNCTIONAL MRI

Psychiatric