Our findings provide robust evidence that obesity and body mass are related to significantly lower gray matter volume in brain areas with a key role in executive control. These findings might suggest a neurobiological link between obesity and self-regulatory deficits.

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Highlights d We performed functional MRI in individuals who undertook a weight-loss regimen d Calorie restriction led to weight loss and leptin and ghrelin adaptations d We uncovered a neural signature of successful weight loss d The best predictor of success was activation in prefrontal cortex during the regime

As anyone who has suffered through a head cold knows, food eaten when the olfactory system is impaired tastes “wrong”–an experience that leads many to conclude that taste stimuli are processed normally only when the olfactory system is unimpaired. Evidence that taste system function influences olfactory perception, meanwhile, has been vanishingly rare. Here, we demonstrate just such an influence, showing that if taste cortex is inactivated when an odor is first presented, later presentations are properly appreciated only if taste cortex is again inactivated.

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Psychosocial stress is associated with an increased intake of palatable foods and weight gain in stress-reactive individuals. Personality traits have been shown to predict stress-reactivity. However, it is not known if personality traits influence brain activity in regions implicated in appetite control during psychosocial stress. The current study assessed whether Gray's Behavioural Inhibition System (BIS) scale, a measure of stress-reactivity, was related to the activity of brain regions implicated in appetite control during a stressful period. Twenty-two undergraduate students participated in a functional magnetic resonance imaging (fMRI) experiment once during a non-exam period and once during final exams in a counter-balanced order. In the scanner, they viewed food and scenery pictures. In the exam compared with the non-exam condition, BIS scores related to increased perceived stress and correlated with increased blood-oxygen-level dependent (BOLD) response to high-calorie food images in regions implicated in food reward and subjective value, such as the ventromedial prefrontal cortex, (vmPFC) and the amygdala. BIS scores negatively related to the functional connectivity between the vmPFC and the dorsolateral prefrontal cortex. The results demonstrate that the BIS trait influences stress reactivity. This is observed both as an increased activity in brain regions implicated in computing the value of food cues and decreased connectivity of these regions to prefrontal regions implicated in self-control. This suggests that the effects of real life stress on appetitive brain function and self-control is modulated by a personality trait. This may help to explain why stressful periods can lead to overeating in vulnerable individuals.

Acute inhibition of acetylcholine (ACh) has been shown to impair many forms of simple learning, and notably conditioned taste aversion (CTA). The most adhered-to theory that has emerged as a result of this work – that ACh increases a taste’s perceived novelty, and thereby its associability – would be further strengthened by evidence showing that enhanced cholinergic function improves learning above normal levels. Experimental testing of this corollary hypothesis has been limited, however, by side-effects of pharmacological ACh agonism and by the absence of a model that achieves long-term increases in cholinergic signaling. Here, we present this further test of the ACh hypothesis, making use of mice lacking the p75 pan-neurotrophin receptor gene, which show a resultant over-abundance of cholinergic neurons in sub-regions of the basal forebrain (BF). We first demonstrate that the p75−/− abnormality directly affects portions of the CTA circuit, locating mouse gustatory cortex (GC) using a functional assay and then using immunohistochemisty to demonstrate cholinergic hyper-innervation of GC in the mutant mice – hyper-innervation that is unaccompanied by changes in cell numbers or compensatory changes in muscarinic receptor densities. We then demonstrate that both p75−/− and wild-type (WT) mice learn robust CTAs, which extinguish more slowly in the mutants. Further testing to distinguish effects on learning from alterations in memory retention demonstrate that p75−/− mice do in fact learn stronger CTAs than WT mice. These data provide novel evidence for the hypothesis linking ACh and taste learning.

23Background 24 Impulsivity is a risk factor for obesity. It has different underlying facets that can be assessed 25 using questionnaires. Impulsivity can be further refined by the use of food-specific 26 questionnaires, which measure a tendency to uncontrolled eating. We examined how these 27 impulsivity measures relate to each other, to obesity, and to brain anatomy. 28 Methods 29We assessed students in their first year of university -a risky period for weight gain-at the 30 beginning (N = 2214) and at the end of the school year (N = 1145) using questionnaire measures 31 of impulsivity, personality, stress reactivity and eating-specific traits. A subset of participants (N 32 = 72) underwent T1-weighted MRI to investigate the brain correlates of impulsivity. 33Results 34Using factor analysis, we show that impulsivity can be stratified into three domains, which we 35 label stress reactivity, reward sensitivity and self-control, while eating questionnaires resolve 36 into a single latent factor -uncontrolled eating. A watershed model shows that uncontrolled 37 eating mediates the effect of impulsivity traits on BMI. Self-control and stress reactivity scores 38 are associated with a thinner lateral orbitofrontal cortex. In addition, stress reactivity correlates 39 positively with amygdala and negatively with hippocampal volume. Longitudinally, lack of self-40 control, not uncontrolled eating, correlates with weight gain, while stress reactivity correlates 41 with weight loss in male students. 42 Conclusions 43The brain-impulsivity-obesity relationship is hierarchical. Structural brain differences relate to 44 differences in impulsivity domains which affect BMI via uncontrolled eating. However, 45 Neseliler et al. Neural and behavioral endophenotypes of obesity 3 longitudinally, low self-control, not uncontrolled eating, is a predictor of weight gain in this 46 sample. 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Neseliler et al. Neural and behavioral endophenotypes of obesity 4