The timing of meals

In most individuals, food intake occurs as discrete bouts or meals, and little attention has been paid to the factors that normally determine when meals will occur when food is freely available. On the basis of experiments using rats, the authors suggest that when there are no constraints on obtaining food and few competing activities, 3 levels of interacting controls normally dictate when meals will start. The first is the genetically determined circadian activity pattern on which nocturnal animals tend to initiate most meals in the dark. The second is the regularly occurring changing of the light cycle: These changes provide temporal anchors. The third relates to the size of the preceding meal, such that larger meals cause a longer delay until the onset of the next meal. Superimposed on these 3 are factors related to learning, convenience, and opportunity

Vicarious ratings of social touch reflect the anatomical distribution & velocity tuning of C-tactile afferents: A Hedonic Homunculus?

A subclass of C-fibres, C-tactile afferents (CTs), have been discovered which respond preferentially to low force/velocity stroking touch, that is typically perceived as pleasant. Molecular genetic visualization of these low-threshold mechanosensitive C-fibres (CLTMs) in mice revealed a denser distribution in dorsal than ventral thoracic sites, scattered distal limb innervation and a complete absence from glabrous paw skin (Liu et al., 2007). Here we used third-party ratings to examine whether affective responses to social touch reflect the anatomical distribution and velocity tuning of CTs. Participants viewed and rated a sequence of video clips depicting one individual being touched by another at different skin sites and at 3 different velocities (static, 3 cm/s, 30 cm/s). Immediately after viewing each clip participants were asked to rate how pleasant they perceived the touch to be. Vicarious preferences matched the previously reported anatomical innervation density of rodent CLTMs, with touch on the back being rated significantly more pleasant than any other location. Furthermore, in contrast to all other skin sites, CT optimal (3 cm/s) touch on the palm of the hand was not preferred to static touch, consistent with the anatomical absence of CTs in glabrous skin. Our findings demonstrate that humans recognise the specific rewarding value of CT optimal caressing touch and their preferences reflect the hypothesised anatomical distribution of CTs

Central insulin and macronutrient intake in the rat

When rats are maintained on a standard laboratory diet, the infusion of low doses of insulin into the cerebroventricular system causes a reduction of food intake and body weight. It was recently reported that, if rats are maintained on a high-fat diet (56% calories as fat), they are insensitive to this action of insulin. To investigate further the effect of dietary composition on responsiveness to central insulin, we carried out two experiments. In experiment 1, rats were maintained on one of four equicaloric diets (providing 7, 22, 39, or 54% of calories as fat) before and during a 6-day third-ventricular infusion (i3vt) of insulin (10 mU/day) or saline. Rats consuming 7 or 22% of calories as fat had a significant reduction of both food intake (-17.2 +/- 2.9 and -14.6 +/- 3.3 g, respectively) and body weight (-50 +/- 5 and -41 +/- 5 g, respectively) from baseline over the insulin-infusion period. Rats consuming 39 or 54% calories as fat did not reliably alter food intake (-4.0 +/- 3.9 and -1.9 +/- 3.7 g, respectively) or body weight (-10 +/- 6 and -6 +/- 4 g, respectively) in response to i3vt of insulin. In experiment 2, rats were offered a choice of three macronutrients (carbohydrates, fats, and proteins) in separate jars in their home cages. After they had adapted to the diets, they were infused i3vt with insulin or saline. Insulin caused a significant reduction of body weight relative to saline-infused controls (body wt: -23.1 +/- 4 g) and a reduction in food intake that was selective for dietary fat. These data suggest that the effects of central insulin administration are highly dependent on the macronutrient content of the diet as well as the ability of rats to select their own diets

Inter and intra-hemispheric structural imaging markers predict depression relapse after electroconvulsive therapy: a multisite study.

Relapse of depression following treatment is high. Biomarkers predictive of an individual's relapse risk could provide earlier opportunities for prevention. Since electroconvulsive therapy (ECT) elicits robust and rapidly acting antidepressant effects, but has a >50% relapse rate, ECT presents a valuable model for determining predictors of relapse-risk. Although previous studies have associated ECT-induced changes in brain morphometry with clinical response, longer-term outcomes have not been addressed. Using structural imaging data from 42 ECT-responsive patients obtained prior to and directly following an ECT treatment index series at two independent sites (UCLA: n = 17, age = 45.41±12.34 years; UNM: n = 25; age = 65.00±8.44), here we test relapse prediction within 6-months post-ECT. Random forests were used to predict subsequent relapse using singular and ratios of intra and inter-hemispheric structural imaging measures and clinical variables from pre-, post-, and pre-to-post ECT. Relapse risk was determined as a function of feature variation. Relapse was well-predicted both within site and when cohorts were pooled where top-performing models yielded balanced accuracies of 71-78%. Top predictors included cingulate isthmus asymmetry, pallidal asymmetry, the ratio of the paracentral to precentral cortical thickness and the ratio of lateral occipital to pericalcarine cortical thickness. Pooling cohorts and predicting relapse from post-treatment measures provided the best classification performances. However, classifiers trained on each age-disparate cohort were less informative for prediction in the held-out cohort. Post-treatment structural neuroimaging measures and the ratios of connected regions commonly implicated in depression pathophysiology are informative of relapse risk. Structural imaging measures may have utility for devising more personalized preventative medicine approaches

Adrenalectomy alters the sensitivity of the central nervous system melanocortin system

Removal of adrenal steroids by adrenalectomy (ADX) reduces food intake and body weight in rodents and prevents excessive weight gain in many genetic and dietary models of obesity. Thus, glucocorticoids appear to play a key role to promote positive energy balance in normal and pathological conditions. By comparison, central nervous system melanocortin signaling provides critical inhibitory tone to regulate energy balance. The present experiments sought to test whether glucocorticoids influence energy balance by altering the sensitivity to melanocortin receptor ligands. Because melanocortin-producing neurons are hypothesized to be downstream of leptin in a key weight-reducing circuit, we tested rats for their sensitivity to leptin and confirmed reports that the hypophagic response to third ventricular (i3vt) leptin is increased in ADX rats and is normalized by glucocorticoid replacement. Next we tested rats for their sensitivity to the melanocortin agonist melanotan II and found that, as for leptin, ADX enhanced the hypophagic response via a glucocorticoid-dependent mechanism. The central nervous system melanocortin system is unique in that it includes the endogenous melanocortin receptor antagonist, AgRP. The orexigenic effect of i3vt AgRP was absent in ADX rats and restored by glucocorticoid replacement. We conclude that the potent weight-reducing effects of ADX likely involve heightened responsiveness to melanocortin receptor stimulation