Elanor C. Hinton

Neural representations of hunger and satiety in Prader–Willi syndrome

Objective:To investigate the neural basis of the abnormal eating behaviour in Prader–Willi syndrome (PWS), using brain imaging. We predicted that the satiety response in those with PWS would be delayed and insensitive to food intake.Design and participants:The design of this study was based on a previous investigation of the neural activation associated with conditions of fasting and food intake in a nonobese, non-PWS group. The findings were used to generate specific hypotheses regarding brain regions of interest for the current study, in which 13 adults with PWS took part (mean±s.d. age=29±6; BMI=31.5±5.1; IQ=71±8, six were female).Measurements:Regional cerebral blood flow was measured using positron emission tomography in three sessions: one following an overnight fast and two following disguised energy controlled meals of similar volume and appearance – one of 1674 kJ (400 kcal) and another of 5021 kJ (1200 kcal). Subjective ratings of hunger, fullness and desire to eat, and blood plasma levels of glucose, insulin, leptin, ghrelin and PYY were measured before and after each imaging session.Results:The neural representation of hunger, after an overnight fast, was similar to that found in nonobese individuals in the control study. In contrast, after food intake, the patterns of neural activation previously associated with satiety were not found, even after the higher-energy load. Lateral and medial orbitofrontal cortical activation was associated with consumption of the 400- and 1200-kcal meals, respectively. The medial orbitofrontal activation, however, was only found in those who had shown a large percentage change in fullness ratings following the higher-energy meal.Conclusion:We conclude that there is a dysfunction in the satiety system in those with PWS. These findings suggest that brain regions associated with satiety are insensitive even to high-energy food intake in those with the syndrome. This may be the neural basis of the hyperphagia seen in PWS.

Computer-based assessments of expected satiety predict behavioural measures of portion-size selection and food intake ☆

Previously, expected satiety (ES) has been measured using software and two-dimensional pictures presented on a computer screen. In this context, ES is an excellent predictor of self-selected portions, when quantified using similar images and similar software. In the present study we sought to establish the veracity of ES as a predictor of behaviours associated with real foods. Participants (N=30) used computer software to assess their ES and ideal portion of three familiar foods. A real bowl of one food (pasta and sauce) was then presented and participants self-selected an ideal portion size. They then consumed the portion ad libitum. Additional measures of appetite, expected and actual liking, novelty, and reward, were also taken. Importantly, our screen-based measures of expected satiety and ideal portion size were both significantly related to intake (p<.05). By contrast, measures of liking were relatively poor predictors (p>.05). In addition, consistent with previous studies, the majority (90%) of participants engaged in plate cleaning. Of these, 29.6% consumed more when prompted by the experimenter. Together, these findings further validate the use of screen-based measures to explore determinants of portion-size selection and energy intake in humans.

The paradox of Prader-Willi syndrome: a genetic model of starvation.

The neurodevelopmental disorder, Prader-Willi syndrome, is generally regarded as a genetic model of obesity. Although the values of some hypothalamic neuropeptides are as expected in obesity, and should result in satiety, we propose that abnormal hypothalamic pathways mean that these are ineffective. We postulate that the body incorrectly interprets the absence of satiation as starvation, and therefore, paradoxically, this syndrome should be redefined as one of starvation that manifests as obesity in a food-rich environment. Also, this syndrome is generally believed to be a contiguous gene disorder, which results from the absence of expression of the paternally derived alleles of maternally imprinted genes on chromosome 15 (15q11-13). We argue, however, that the whole phenotype can be explained by one mechanism and, by implication, the failure of expression of the paternal allele of a single maternally imprinted gene that controls energy balance. We suggest clinical and laboratory approaches to test our hypotheses.

Episodic Memory and Appetite Regulation in Humans

Psychological and neurobiological evidence implicates hippocampal-dependent memory processes in the control of hunger and food intake. In humans, these have been revealed in the hyperphagia that is associated with amnesia. However, it remains unclear whether ‘memory for recent eating’ plays a significant role in neurologically intact humans. In this study we isolated the extent to which memory for a recently consumed meal influences hunger and fullness over a three-hour period. Before lunch, half of our volunteers were shown 300 ml of soup and half were shown 500 ml. Orthogonal to this, half consumed 300 ml and half consumed 500 ml. This process yielded four separate groups (25 volunteers in each). Independent manipulation of the ‘actual’ and ‘perceived’ soup portion was achieved using a computer-controlled peristaltic pump. This was designed to either refill or draw soup from a soup bowl in a covert manner. Immediately after lunch, self-reported hunger was influenced by the actual and not the perceived amount of soup consumed. However, two and three hours after meal termination this pattern was reversed - hunger was predicted by the perceived amount and not the actual amount. Participants who thought they had consumed the larger 500-ml portion reported significantly less hunger. This was also associated with an increase in the ‘expected satiation’ of the soup 24-hours later. For the first time, this manipulation exposes the independent and important contribution of memory processes to satiety. Opportunities exist to capitalise on this finding to reduce energy intake in humans.

NEURAL CORRELATES OF RELATIONAL REASONING AND THE SYMBOLIC DISTANCE EFFECT: INVOLVEMENT OF PARIETAL CORTEX

A novel, five-term relational reasoning paradigm was employed during functional magnetic resonance imaging to investigate neural correlates of the symbolic distance effect (SDE). Prior to scanning, participants learned a series of more-than (E>D>C>B>A) or less-than (A<B<C<D<E) ordered premise pairs. During scanning, inferential tests presented the premise pairs, adjacent, mutually entailed tasks (e.g., D<E and B>A) and nonadjacent one-step (A<C, B<D, C<E, C>A, D>B and E>C) and two-step (A<D, B<E, D>A and E>B) combinatorial entailed tasks. In terms of brain activation, the SDE was identified in the inferior frontal cortex, dorsolateral prefrontal cortex, and bilateral parietal cortex with a graded activation pattern from adjacent to one-step and two-step relations. We suggest that this captures the behavioural SDE of increased accuracy and decreased reaction time from adjacent to two-step relations. One-step relations involving endpoints A or E resulted in greater parietal activation compared to one-step relations without endpoints. Novel contrasts found enhanced activation in right parietal and prefrontal cortices during mutually entailed tasks only for participants who had learned all less-than relations. Increased parietal activation was found for one-step tasks that were inconsistent with prior training. Overall, the findings demonstrate a crucial role for parietal cortex during relational reasoning with a spatially ordered array.

Preference judgements involve a network of structures within frontal, cingulate and insula cortices

Environmental stimuli constantly compete for human attention and in many cases decisions are made based on the affective meaning they convey. Although the network of structures involved in processing affective value has been well described, the specific contribution of these structures to the process by which affective value guides decision making is less well understood and is the focus of the present study. Thus, subjects read descriptions of individually tailored holidays, varying in incentive value and then made preference judgements, cognitive judgements or no decision. Choices made from an affective perspective, compared with those made from a cognitive perspective, activated a region of the anterior insula/operculum and also the anterior cingulate cortex. Furthermore, activity in perigenual, anterior cingulate cortex was correlated with subjective ratings of incentive value. In contrast, medial orbitofrontal cortex (OFC) and a region of posterior ventrolateral prefrontal cortex (PFC), bordering on the insula, were found to be more active when affective stimuli guided response selection than when no selection was made. However, only the activity in the ventrolateral PFC was specific to response selection based on affective compared with cognitive judgements. It is proposed that the necessary introspection required to make subjective preference judgements is provided by the insula and cingulate cortices, while the medial OFC and posterior ventrolateral PFC/insula cortices contribute to stimulus evaluation and motivational aspects of response selection, respectively.

Product labelling can confer sustained increases in expected and actual satiety

Expected satiety has been shown to play a key role in decisions around meal size. Recently it has become clear that these expectations can also influence the satiety that is experienced after a food has been consumed. As such, increasing the expected and actual satiety a food product confers without increasing its caloric content is of importance. In this study we sought to determine whether this could be achieved via product labelling. Female participants (N=75) were given a 223-kcal yoghurt smoothie for lunch. In separate conditions the smoothie was labelled as a diet brand, a highly-satiating brand, or an ‘own brand’ control. Expected satiety was assessed using rating scales and a computer-based ‘method of adjustment’, both prior to consuming the smoothie and 24 hours later. Hunger and fullness were assessed at baseline, immediately after consuming the smoothie, and for a further three hours. Despite the fact that all participants consumed the same food, the smoothie branded as highly-satiating was consistently expected to deliver more satiety than the other ‘brands’; this difference was sustained 24 hours after consumption. Furthermore, post-consumption and over three hours, participants consuming this smoothie reported significantly less hunger and significantly greater fullness. These findings demonstrate that the satiety that a product confers depends in part on information that is present around the time of consumption. We suspect that this process is mediated by changes to expected satiety. These effects may potentially be utilised in the development of successful weight-management products.

Excessive appetitive arousal in Prader–Willi syndrome

This study focused on genetic and behavioural aspects of one important component of the motivation to eat - how appetitive arousal is elicited through the presentation of food-associated stimuli. Individuals with Prader-Willi syndrome, a genetic disorder associated with hyperphagia, and control participants completed a computerised response task in the presence of motivational stimuli. In controls, appetitive arousal was specific to particular stimuli. In contrast, individuals with PWS showed a non-specific pattern of arousal. Over-activation of the anticipatory motivation system may be one consequence of the genetic disorder in PWS.

Reasoning with linear orders: differential parietal cortex activation in sub-clinical depression. An FMRI investigation in sub-clinical depression and controls.

The capacity to learn new information and manipulate it for efficient retrieval has long been studied through reasoning paradigms, which also has applicability to the study of social behavior. Humans can learn about the linear order within groups using reasoning, and the success of such reasoning may vary according to affective state, such as depression. We investigated the neural basis of these latter findings using functional neuroimaging. Using BDI-II criteria, 14 non-depressed (ND) and 12 mildly depressed volunteers took part in a linear-order reasoning task during functional magnetic resonance imaging. The hippocampus, parietal, and prefrontal cortices were activated during the task, in accordance with previous studies. In the learning phase and in the test phase, greater activation of the parietal cortex was found in the depressed group, which may be a compensatory mechanism in order to reach the same behavioral performance as the ND group, or evidence for a different reasoning strategy in the depressed group.