Biology subjects

Janssen, L. K.

Publications and source records attributed to Janssen, L. K..

4 recordsLinked to original sources

bioRxiv2017

Spontaneous eye blink rate and dopamine synthesis capacity: Preliminary evidence for an absence of positive correlation

Dopamine is central to a number of cognitive functions and brain disorders. Given the cost of neurochemical imaging in humans, behavioral proxy measures of dopamine have gained in popularity in the past decade, such as spontaneous eye blink rate (sEBR). Increased sEBR is commonly associated with increased dopamine function based on pharmacological evidence and patient studies. Yet, this hypothesis has not been validated using in vivo measures of dopamine function in humans. In order to fill this gap, we measured sEBR and striatal dopamine synthesis capacity using [18F]DOPA PET in 20 participants (9 healthy individuals and 11 pathological gamblers). Our results, based on frequentist and Bayesian statistics, as well as region-of-interest and voxel-wise analyses, argue against a positive relationship between sEBR and striatal dopamine synthesis capacity. They show that, if anything, the evidence is in favor of a negative relationship. These results, which complement findings from a recent study that failed to observe a relationship between sEBR and dopamine D2 receptor availability, suggest that caution and nuance are warranted when interpreting sEBR in terms of a proxy measure of striatal dopamine.

neuroscience↗

bioRxiv2017

Enhanced food-related responses in the ventral medial prefrontal cortex in orexin-deficient narcolepsy patients

BackgroundNarcolepsy Type 1 is a chronic sleep disorder caused by a deficiency of orexin (hypocretin). In addition to sleep regulation, orexin is important for motivated control processes. Weight gain and obesity are common in narcolepsy. However, the neurocognitive processes associated with food-related control and overeating in orexin-deficient patients are unknown. We explored the neural correlates of general and food-related attentional control in narcolepsy patients (n=23) and healthy BMI-matched controls (n=20). In secondary analyses, we included patients with idiopathic hypersomnia (n=15) to assess sleepiness-related influences.\n\nMethodsWe measured attentional bias to food words with a Food Stroop task and general executive control with a Classic Stroop task during fMRI. Moreover, with correlational analyses, we assessed the relative contribution of the neural findings on the Food Stroop and Classic Stroop tasks to spontaneous snack intake.\n\nResultsRelative to healthy controls, narcolepsy patients showed enhanced ventral medial prefrontal cortex responses and connectivity with motor cortex during the Food Stroop task, but attenuated dorsal medial prefrontal cortex responses during the Classic Stroop task. The ventral medial prefrontal cortex responses on the Food Stroop task, not the dorsal medial prefrontal cortex responses on the Classic Stroop task, were a significant predictor of snack intake. Comparing the narcolepsy patients with idiopathic hypersomnia patients revealed similar results.\n\nConclusionsThese findings demonstrate that orexin deficiency is associated with decreased dorsal medial prefrontal cortex responses during general executive control and enhanced ventral medial prefrontal cortex responses during food-driven attention, with the latter predicting increases in food intake.\n\nStatement of SignificancePatients with orexin (hypocretin) deficient narcolepsy type-1 often suffer from obesity as well as increased food craving, in addition to the sleep symptoms. However, whether and how orexin deficiency relates to neural differences in food-directed attention is unclear. We employed a Food Stroop task during fMRI and provide experimental evidence that the ventral medial prefrontal cortex responds more strongly to food words in narcolepsy patients than in controls. The hypothesis that this mechanism contributes to weight problems in narcolepsy is strengthened by the observation that ventral medial prefrontal cortex responses during the Food Stroop task were predictive of snack intake. These mechanistic data might thus advance the development of treatment targets for obesity in narcolepsy.

neuroscience↗

bioRxiv2017

Dopaminergic drug effects on probability weighting during risky decision-making

Dopamine has been associated with risky decision-making, as well as with pathological gambling, a behavioural addiction characterized by excessive risk-taking behaviour. However, the specific mechanisms through which dopamine might act to foster risk-taking and pathological gambling remain elusive. Here we test the hypothesis that this might be achieved, in part, via modulation of subjective probability weighing during decision-making. Healthy controls (n = 21) and pathological gamblers (n = 16) played a decision-making task involving choices between sure monetary options and risky gambles both in the gain and loss domains. Each participant played the task twice, either under placebo or the dopamine D2/D3 receptor antagonist sulpiride, in a double-blind, counter-balanced, design. A prospect theory modelling approach was used to estimate subjective probability weighting and sensitivity to monetary outcomes. Consistent with prospect theory, we found that participants presented a distortion in the subjective weighting of probabilities, i.e. they overweighted low probabilities and underweighted moderate to high probabilities, both in the gain and loss domains. Compared with placebo, sulpiride attenuated this distortion in the gain domain. Across drugs, the groups did not differ in their probability weighting, although in the placebo condition, gamblers consistently underweighted losing probabilities. Overall, our results reveal that dopamine D2/D3 receptor antagonism modulates the subjective weighting of probabilities in the gain domain, in the direction of more objective, economically rational decision-making.\n\nSignificance statementDopamine has been implicated in risky decision-making and gambling addiction, but the exact mechanisms underlying this influence remain partly elusive. Here we tested the hypothesis that dopamine modulates subjective probability weighting, by examining the effect of a dopaminergic drug on risk-taking behaviour, both in healthy individuals and pathological gamblers. We found that selectively blocking dopamine D2/D3 receptors diminished the typically observed distortion of winning probabilities, characterized by an overweighting of low probabilities and underweighting of high probabilities. This made participants more linear in their subjective estimation of probabilities, and thus more rational in their decision-making behaviour. Healthy participants and pathological gamblers did not differ in their risk-taking behaviour, except in the placebo condition in which gamblers consistently underweighted losing probabilities.

neuroscience↗

bioRxiv2017

The effect of an 8-week mindful eating intervention on anticipatory reward responses in the midbrain

Obesity is a highly prevalent disease, usually resulting from chronic overeating. Accumulating evidence suggests that increased neural responses during the anticipation of high-calorie food play an important role in overeating. A promising method for counteracting enhanced food anticipation in overeating might be mindfulness-based interventions (MBIs). However, the neural mechanisms by which MBIs can affect food reward anticipation are unclear. In this randomized, actively controlled study, the primary objective was to investigate the effect of an 8-week mindful eating intervention on reward anticipation. On the neural level, we hypothesized that mindful eating would decrease striatal reward anticipation responses. Additionally, responses in the midbrain - from which the reward pathways originate - were explored. Using functional magnetic resonance imaging (fMRI), we tested 58 healthy participants with a wide body mass index range (BMI: 19-35 kg/m2), motivated to change their eating behavior. During scanning they performed an incentive delay task, measuring neural reward anticipation responses to caloric and monetary cues before and after 8 weeks of mindful eating or educational cooking (active control). Compared with the educational cooking intervention, mindful eating affected neural reward anticipation responses, with relatively reduced caloric versus monetary reward responses. This effect was, however, not seen in the striatum, but only in the midbrain. The secondary objective was to assess temporary and long-lasting (one year follow-up) intervention effects on self-reported eating behavior and anthropometric measures (BMI, waist circumference, waist-to-hip-ratio (WHR)). We did not observe effects of the mindful eating intervention on eating behavior. Instead, the control intervention showed temporary beneficial effects on BMI, waist circumference, and diet quality, but not on WHR or self-reported eating behavior, as well as long-lasting increases in knowledge about healthy eating. These results suggest that an 8-week mindful eating intervention may have decreased the relative salience of food cues by affecting midbrain but not striatal reward responses. However, these exploratory results should be verified in confirmatory research. The primary and secondary objectives of the study were registered in the Dutch Trial Register (NTR): NL4923 (NTR5025).

neuroscience↗