A randomized controlled trial investigating the effect of liraglutide on self-reported liking and neural responses to food stimuli in participants with obesity.

BACKGROUND/OBJECTIVES: Obesity is a complex condition and the mechanisms involved in weight gain and loss are not fully understood. Liraglutide, a GLP-1 receptor agonist, has been demonstrated to successfully promote weight loss in patients with obesity (OB). Yet, it is unclear whether the observed weight loss is driven by an alteration of food liking. Here we investigated the effects of liraglutide on food liking and the cerebral correlates of liking in OB. SUBJECTS/METHODS: This study was a randomized, single-center, double-blind, placebo-controlled, parallel group, prospective clinical trial. 73 participants with OB and without diabetes following a multidisciplinary weight loss program, were randomly assigned (1:1) to receive liraglutide 3.0 mg (37.40 ± 11.18 years old, BMI = 35.89 ± 3.01 kg) or a placebo (40.04 ± 14.10 years old, BMI = 34.88 ± 2.87 kg) subcutaneously once daily for 16 weeks. INTERVENTIONS/METHODS: We investigated liking during food consumption. Participants reported their hedonic experience while consuming a high-calorie food (milkshake) and a tasteless solution. The solutions were administered inside the scanner with a Magnetic Resonance Imaging (MRI)-compatible gustometer to assess neural responses during consumption. The same procedure was repeated during the pre- and post-intervention sessions. RESULTS: None of the effects involving the intervention factor reached significance when comparing liking between the pre- and post-intervention sessions or groups. Liking during food reward consumption was associated with the activation of the ventromedial prefrontal cortex (vmPFC) and the amygdala. The liraglutide group lost more weight (BMI post-pre = -3.19 ± 1.28 kg/m2) than the placebo group (BMI post-pre = -0.60 ± 1.26 kg/m2). CONCLUSIONS: These results suggest that liraglutide leads to weight loss without self-report or neural evidence supporting a concomitant reduction of food liking in participants with OB.

Embodied emotion impairment in Huntington's Disease.

Theories of embodied cognition suggest that perceiving an emotion involves somatovisceral and motoric re-experiencing. Here we suggest taking such an embodied stance when looking at emotion processing deficits in patients with Huntington's Disease (HD), a neurodegenerative motor disorder. The literature on these patients' emotion recognition deficit has recently been enriched by some reports of impaired emotion expression. The goal of the study was to find out if expression deficits might be linked to a more motoric level of impairment. We used electromyography (EMG) to compare voluntary emotion expression from words to emotion imitation from static face images, and spontaneous emotion mimicry in 28 HD patients and 24 matched controls. For the latter two imitation conditions, an underlying emotion understanding is not imperative (even though performance might be helped by it). EMG measures were compared to emotion recognition and to the capacity to identify and describe emotions using alexithymia questionnaires. Alexithymia questionnaires tap into the more somato-visceral or interoceptive aspects of emotion perception. Furthermore, we correlated patients' expression and recognition scores to cerebral grey matter volume using voxel-based morphometry (VBM). EMG results replicated impaired voluntary emotion expression in HD. Critically, voluntary imitation and spontaneous mimicry were equally impaired and correlated with impaired recognition. By contrast, alexithymia scores were normal, suggesting that emotion representations on the level of internal experience might be spared. Recognition correlated with brain volume in the caudate as well as in areas previously associated with shared action representations, namely somatosensory, posterior parietal, posterior superior temporal sulcus (pSTS) and subcentral sulcus. Together, these findings indicate that in these patients emotion deficits might be tied to the "motoric level" of emotion expression. Such a double-sided recognition and expression impairment may have important consequences, interrupting empathy in nonverbal communication both ways (understanding and being understood), independently of intact internal experience of emotion.

Distinct frontal and amygdala correlates of change detection for facial identity and expression.

Recruitment of 'top-down' frontal attentional mechanisms is held to support detection of changes in task-relevant stimuli. Fluctuations in intrinsic frontal activity have been shown to impact task performance more generally. Meanwhile, the amygdala has been implicated in 'bottom-up' attentional capture by threat. Here, 22 adult human participants took part in a functional magnetic resonance change detection study aimed at investigating the correlates of successful (vs failed) detection of changes in facial identity vs expression. For identity changes, we expected prefrontal recruitment to differentiate 'hit' from 'miss' trials, in line with previous reports. Meanwhile, we postulated that a different mechanism would support detection of emotionally salient changes. Specifically, elevated amygdala activation was predicted to be associated with successful detection of threat-related changes in expression, over-riding the influence of fluctuations in top-down attention. Our findings revealed that fusiform activity tracked change detection across conditions. Ventrolateral prefrontal cortical activity was uniquely linked to detection of changes in identity not expression, and amygdala activity to detection of changes from neutral to fearful expressions. These results are consistent with distinct mechanisms supporting detection of changes in face identity vs expression, the former potentially reflecting top-down attention, the latter bottom-up attentional capture by stimulus emotional salience.

Reactivation of visual cortex during memory retrieval: content specificity and emotional modulation.

Studies on memory retrieval suggest a reactivation of cortical regions engaged during encoding, such that visual or auditory areas reactivate for visual or auditory memories. The content specificity and any emotion dependency of such reactivations are still unclear. Because distinct visual areas are specialized in processing distinct stimulus categories, we tested for face and word specific reactivations during a memory task using functional magnetic resonance imaging (fMRI). Furthermore, because visual processing and memory are both modulated by emotion, we compared reactivation for stimuli encoded in a neutral or emotionally significant context. In the learning phase, participants studied pairs of stimuli that consisted of either a scene and a face, or a scene and a word. Scenes were either neutral or negative, but did not contain faces or words. In the test phase scenes were presented alone (one in turn), and participants indicated whether it was previously paired with a face, a word, or was new. Results from the test phase showed activation in a functionally defined face-responsive region in the right fusiform gyrus, as well as in a word-responsive region in the left inferior temporal gyrus, for scenes previously paired with faces and words, respectively. Reactivation tended to be larger in both the face- and word-responsive regions when the associated scene was negative as compared to neutral. However, relative to neutral context, the recall of faces and words paired with a negative context produced smaller activations in brain regions associated with social and semantic processing, respectively, as well as poorer memory performance overall. Taken together, these results support the idea of cortical memory reactivations, even at a content-specific level, and further suggest that emotional context may produce opposite effects on reactivations in early sensory areas and more elaborate processing in higher-level cortical areas.

Bayesian models of mentalizing.

Surprisingly effortless is the human capacity known as "mentalizing", i.e., the ability to explain and predict the behavior of others by attributing to them independent mental states, such as beliefs, desires, emotions or intentions. This capacity is, among other factors, dependent on the correct anticipation of the dynamics of facially expressed emotions based on our beliefs and experience. Important information about the neural processes involved in mentalizing can be derived from dynamic recordings of neural activity such as the EEG. We here exemplify how the so-called Bayesian probabilistic models can help us to model the neural dynamic involved in the perception of clips that evolve from neutral to emotionally laden faces. Contrasting with conventional models, in Bayesian models, probabilities can be used to dynamically update beliefs based on new incoming information. Our results show that a reproducible model of the neural dynamic involved in the appraisal of facial expression can be derived from the grand mean ERP over five subjects. One of the two models used to predict the individual subject dynamic yield correct estimates for four of the five subjects analyzed. These results encourage the future use of Bayesian formalism to build more detailed models able to describe the single trial dynamic.

Simultaneous recording of EEG and facial muscle reactions during spontaneous emotional mimicry.

The perception of emotional facial expressions induces covert imitation in emotion-specific muscles of the perceiver's face. Neural processes involved in these spontaneous facial reactions remain largely unknown. Here we concurrently recorded EEG and facial EMG in 15 participants watching short movie clips displaying either happy or angry facial expressions. EMG activity was recorded for the zygomaticus major (ZM) that elevates the lips during a smile, and the corrugator supercillii (CS) that knits the eyebrows during a frown. We found increased EMG activity of CS in response to angry expressions, and enhanced EMG activity of ZM for happy expressions, replicating earlier EMG studies. More importantly, we found that the amplitude of an early visual evoked potential (right P1) was larger when ZM activity to happy faces was high, and when CS activity to angry faces was high, as compared to when muscle reactions were low. Conversely, the amplitude of right N170 component was smaller when the intensity of facial imitation was high. These combined EEG-EMG results suggest that early visual processing of face expression may determine the magnitude of subsequent facial imitation, with dissociable effects for P1 and N170. These findings are discussed against the classical dual-route model of face recognition.