Marianne Patt

Introduction: Music listening reliably induces arousal in the listener, however its effect on dopaminergic transmission is not yet fully explored. Material and methods: We investigated the responsiveness of the striatal dopamine D1 receptor (D1R) system, which is preferentially engaged by phasic dopaminergic signals, using simultaneous PET-fMRI and the selective D1R radioligand [ ¹¹ C]SCH23390. Fifteen neurotypical participants were scanned during silence before listening to a music piece in its pleasant and unpleasantly manipulated variation. Striatal binding potential (BP _ND ) was significantly lower when listening to music compared to silence. Results: A seed-based fMRI analysis revealed higher functional connectivity between the striatum and left dorsolateral pre-frontal cortex (MNI: x = -43, y = 24, z = 24) during pleasant music in relation to unpleasant music. An exploratory whole-brain D1R PET analysis further identified increased insular BP _ND (MNI: x = -33, y = 1.5, z = 16.5; T = 5.58) during pleasant relative to unpleasant music. Comparison of BP _ND and fMRI beta estimates changes within that prefrontal cluster showed a moderate correlation between the pleasant and unpleasant music condition (R = -0.52, p = 0.046), but no correlation for the silent conditions (R = 0.24, p = 0.42). Changes in ratings of musical pleasantness moderately correlated with fMRI changes in the prefrontal cluster, but not with changes in BP _ND . Conclusion: Our results demonstrate that music irrespective of valence engages the D1R system, indicating that the inherently phasic nature of music can drive D1R-related responses. Furthermore, our results demonstrate valence effects in functional connectivity between the striatum and the left dorsolateral prefrontal cortex when listening to music with varying pleasantness.

Cholinergic modulation of brain reward circuitry appears to play a crucial role in information processing about salience as a key biological mechanism in obesity. However, changes in acetylcholine transmission leading to abnormal eating behavior have not been demonstrated in vivo in human obesity. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we found an increased α4β2* nicotinic acetylcholine receptors (nAChR) availability in response to visually salient food cues in twenty individuals with obesity, particularly in those with high disinhibited eating behavior, whereas there was no change in sixteen volunteers served as normal weight control. This increase was accompanied by a shift from dorsal attention network activation in normal-weight controls to salience network activation in individuals with obesity indicating fundamental differences in sensory cue detection. These data should encourage further investigations into α4β2* nAChR in obesity, particularly with regard to treatment with nicotinic receptor agonists for weight loss targeting hedonic overeating.

Objective: The neurobehavioral underpinnings of binge‐eating disorder (BED), co‐occurring with obesity (OB), are largely unknown. This research project conceptualizes BED as a disorder with dysfunctional emotion regulation (ER) linked with changes in central noradrenaline (NA) transmission and NA‐modulated neuronal networks.Methods: We expect abnormalities in NA activity in both BED and OB, but most pronounced in BED. We expect these abnormalities to be modifiable through state‐of‐the‐art ER intervention, specifically in BED. To assess the role of NA transmission, we will quantify changes in NA transporter (NAT) availability using the highly NAT‐specific [¹¹C]methylreboxetin (MRB) and positron emission tomography‐magnetic resonance imaging (PET‐MRI) that allows measuring molecular and neuronal changes before and after an ER intervention. Individual 12‐session smartphone‐supported acceptance‐based behavioral therapy will be conducted to improve ER. Thirty individuals with OB and BED (OB + BED), 30 individuals with OB without BED (OB ‐ BED), and 20 individuals with normal weight will undergo assessments of NAT availability and neuronal network activity under rest and stimulated conditions, clinical interviews, self‐report questionnaires on eating behavior, ER, mental and physical health, and quality of life, and neuropsychological tests on executive function. Afterwards, in an experimental randomized‐controlled design, individuals with OB + BED and OB ‐ BED will be allocated to smartphone‐supported ER intervention versus a waitlist and re‐assessed after 10 weeks.Discussion: By obtaining biological and behavioral markers, the proposed study will disentangle the involvement of NAT and the central NA system in the modulation of emotion‐supporting neuronal networks that influence eating behavior. Neurobehavioral mechanisms of change during an ER intervention will be determined.Trial Registration: German Clinical Trials Register (DRKS): DRKS00029367.Public Significance: This study investigates the central noradrenaline system by using hybrid brain imaging in conjunction with emotion regulation as a putative core biological mechanism in individuals with obesity with or without binge‐eating disorder that is targeted by emotion regulation intervention. The results will provide a molecular signature beyond functional imaging biomarkers as a predictive biomarker toward precision medicine for tailoring treatments for individuals with binge‐eating disorders and obesity.

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