Biology subjects

Haffen, E.

Publications and source records attributed to Haffen, E..

10 recordsLinked to original sources

bioRxiv2025

Novel fat-taste enhancers modulate functional connectivity of the reward system following sustained activation of gustatory pathways in mice

Humans and rodents exhibit an innate preference for dietary fat, and dysfunction of lingual fat-taste receptors CD36 and GPR120 in obesity suggests that impaired oro-sensory lipid detection may contribute to its development. Rodent models with reduced fat-taste sensitivity display increased fat intake, highlighting the role of taste perception in dietary regulation. The newly developed NKS-3 and NKS-5, high-affinity agonists for CD36 and CD36/GPR120 receptors, respectively, induce early fat satiation and reduce both fat-rich food intake and body weight gain in diet-induced obese mice. However, the neural mechanisms underlying these effects remain unclear. Here, we investigated the response of the reward system to a sustained activation of CD36 and GPR120 via fat-taste enhancers NKS-3 and NKS-5 compared to linoleic acid (LA). Male C57BL/6JRj mice (N=88) received oral administration of vehicle, 0.2% LA, 50 {micro}M NKS-3 or 75 {micro}M NKS-5 for 10 days. The immunohistochemical analysis of cerebral FosB neuronal expression revealed a reorganization of the functional network connectivity. Behavioral assessments over an additional 10-day period in a second cohort of animals detected no adverse motivational, compulsive-like, depressive or anxiogenic effect of the treatments. Our findings suggest that our fat-taste enhancers may offer a promising therapeutic strategy against obesity, leveraging the oral-gut-brain axis to regulate fat-rich food intake.

neuroscience↗

bioRxiv2024

Neurovascular unit adjustments following chronic distress explain motivational deficits in mice

BackgroundThe neurovascular unit (NVU) represents the structural and functional relationship between the neural tissue and the blood. Neurovascular dysfunction has been highlighted in neuropsychiatric afflictions, but whether it is a cause or a consequence of the pathology remains to be elucidated. Thus, to elucidate the role of the NVU on the emergence of emotional-cognitive dysfunction, it is necessary to study how its individual components associate. This study therefore aims at investigating whether the development of depressive-related loss of motivation is grounded on NVU adjustments impacting the permeability of the blood-brain barrier (BBB) and in particular, of the structural scaffolding of microvessels. MethodsAdult male C57BL/6jRj mice chronically treated with corticosterone (CORT) and showing severe motivational deficits in an operant progressive ratio (PR) schedule of reinforcement task, presented altered neural activation assessed through FosB expression in key brain regions involved in motivational processing (anterior insular cortex, basolateral amygdala, bed nucleus of the stria terminalis and ventral tegmental area). We evaluated NVU modifications through immunofluorescence staining targeting specific markers of microglia (IBA-1), endothelial tight junctions (ZO-1) and astrocytes (GFAP). The effect of chronic CORT administration on mice BBB permeability was evaluated through in vivo perfusion of fluorescent 40 kDa Dextran. ResultsOur results highlight that where sustained neuronal activation failed, NVU modifications predict behavioural deficits in CORT-treated animals. Notably, our analyses show that NVU modifications within the ventral tegmental area are essential to understand effort-based related behavioural performance in mice, and most particularly, that the key element of microvessels tight junctions ZO-1 plays a pivotal role on motivation-related behavioural output. ConclusionsOur results confirm a direct role of neurovascular adaptations on emotional and cognitive behavioural performance in mice, and therefore place the NVU in a key position in the research of the biological substrate at the origin of neuropsychiatric disorders.

neuroscience↗

bioRxiv2023

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder

ImportanceExamining translatable mitochondrial blood-based biological markers to identify its association with metabolic diseases in bipolar disorder. ObjectiveTo test whether mitochondrial metabolites, mainly lactate, and cell-free circulating mitochondrial DNA are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. DesignIn a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder was conducted, including baseline plasma samples and blinded observers for all experimentation and analysis. SettingThe FondaMental Foundation coordinate a multicenter, multidisciplinary French networks aiming at creation of cohorts to improve identification of homogeneous subgroups of psychiatric disorders toward personalized treatments. ParticipantsThe FACE-BD primary testing cohort includes 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 235 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Participants were randomly selected based on biosample availability. ExposuresAll patients underwent the standard primary care within their center. No intentional exposures were part of this study. Main Outcome and MeasuresThe primary outcome modelled an association with lactate and metabolic syndrome in this population. Reflective a priori hypothesis. ResultsMultivariable regression analyses show lactate association with triglycerides (Est= 0.072(0.023), p = 0.0065,), fasting glucose (Est = 12(0.025), p= 0.000015) and systolic (Est= 0.003(0.0013), p= 0.031) and diastolic blood pressure (Est = 0.0095{+/-}0.0017, p= 1.3e-7). Significantly higher levels of lactate were associated with presence of metabolic syndrome (Est = 0.17{+/-}0.049, p=0.00061) after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. Conclusion & RelevanceThis thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, whereas circulating cell-free mitochondrial DNA is limited in the context of metabolic syndrome. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities. Key PointsO_ST_ABSQuestionC_ST_ABSCan lactate, a mitochondrial metabolite, indicate metabolic syndrome in bipolar disorder? FindingIn 837 stable bipolar disorder patients, we found high lactate levels significantly associated with metabolic syndrome, unlike circulating cell-free mitochondrial DNA. This pattern also appeared in acute bipolar and schizophrenia cases. Mitochondrial-targeted metabolomics distinguishes patients with high lactate and metabolic syndrome from those without lactate changes, but presence of metabolic syndrome. MeaningThis research underscores lactate as a potential biomarker for identifying bipolar disorder patients with metabolic syndrome. It opens new avenues for personalized treatment strategies, leveraging mitochondrial metabolite profiling to improve patient stratification and therapeutic outcomes.

neuroscience↗

bioRxiv2023

Linoleic acid supplementation reverses microglial response to diet induced-obesity at hypothalamic, cortical and subcortical level in mice

Obesity is a major risk factor for neuropsychiatric alterations. Fatty regimes lead to systemic and cerebral inflammation, the latest acting through lipotoxicity on hypothalamic structures controlling energy homeostasis. Since literature points to a protective effect of linoleic acid (LA) on mood disorders through the regulation of systemic inflammation, we investigated how five weeks of LA supplementation modulates emotional behaviour and microglia-related neuroinflammation. C57BL/6j mice were fed with either a high-fat (HFD) or a standard diet for 12 weeks, underwent a battery of behavioural tests and were subsequently sacrificed for immunofluorescence staining targeting microglia-specific calcium-binding proteins (IBA-1). Neuroinflammation severity was approximated in multiple hypothalamic, cortical and subcortical regions. Our results show an anxio-depressive-like effect of sustained HFD that neither was alleviated nor worsen with LA supplementation. Increased IBA-1 expression in the HFD group was substantially reversed with LA supplementation. Thus, our results suggest anti-neuroinflammatory properties of LA not restricted to hypothalamic areas, but also evident at the cortical and subcortical level. This study is therefore relevant in the frame of obesity and neuropsychiatric disorders with a neuroinflammatory basis. Further investigation may provide more information to justify dietary strategies aiming at reducing the impact of obesity associated comorbidities.

neuroscience↗

bioRxiv2023

Acute effect of transcranial direct current stimulation (tDCS) on postural control of trained athletes: a randomized controlled trial

Transcranial direct current stimulation (tDCS) is used to modulate the brain function in targeted brain areas, and can acutely modulate motor control, such as postural control. While the acute effect of tDCS is well documented on patients, little is still known whether tDCS can alter the motor control of healthy populations with an already high level of motor skills. This study aimed to assess the acute effect of tDCS on postural control of trained athletes. Eighteen parkour practitioners, known for their good balance abilities, were tested on three occasions in the laboratory for each stimulation condition (2 mA ; 20 minutes) - primary motor cortex (M1), prefrontal cortex (dlPFC) and sham (placebo). Postural control was evaluated PRE and POST each stimulation by measuring Center of Pressure (CoP) displacements on a force platform during static conditions (bipedal and unipedal stance). Following M1 stimulation, significant decreases were observed in CoP area in unipedal (P=0.003) and bipedal (P<0.001) stances. As well, the CoP total length was significantly reduced in bipodal (P=0.005) as well as in unipedal stance (P<0.001), only after M1 stimulation. Relative pre-post changes observed after M1 stimulation were negatively correlated to experience in parkour only after unipedal stance (r=0.715, P<0.001), meaning that the more participants were trained the less tDCS was effective. No significant changes were noticed after sham and dlPFC stimulation. These results suggested that the modulation of gait performance in athletes following an acute intervention of tDCS is specific to the targeted brain region, and that more complex postures (such as unipedal stance) were more sensitive to the effect of tDCS according to the level of practice.

neuroscience↗

bioRxiv2021

Three simple steps to improve the interpretability of EEG-SVM studies

Research in machine-learning classification of electroencephalography (EEG) data offers important perspectives for the diagnosis and prognosis of a wide variety of neurological and psychiatric conditions, but the clinical adoption of such systems remains low. We propose here that much of the difficulties translating EEG-machine learning research to the clinic result from consistent inaccuracies in their technical reporting, which severely impair the interpretability of their often-high claims of performance. Taking example from a major class of machine-learning algorithms used in EEG research, the support-vector machine (SVM), we highlight three important aspects of model development (normalization, hyperparameter optimization and cross-validation) and show that, while these 3 aspects can make or break the performance of the system, they are left entirely undocumented in a shockingly vast majority of the research literature. Providing a more systematic description of these aspects of model development constitute three simple steps to improve the interpretability of EEG-SVM research and, in fine, its clinical adoption.

neuroscience↗

bioRxiv2021

Chronic distress in male mice impairs motivation compromising both effort and reward processing with altered anterior insular cortex and basolateral amygdala neural activation

In humans and mammals, effort-based decision-making for monetary or food rewards paradigms contribute to the study of adaptive goal-directed behaviours acquired through reinforcement learning. Chronic distress modelled by repeated exposure to glucocorticoids in rodents induces suboptimal decision-making under uncertainty by impinging on instrumental acquisition and prompting negative valence behaviours. In order to further disentangle the motivational tenets of adaptive decision-making, this study addressed the consequences of enduring distress on relevant effort and reward processing dimensions. Experimentally, appetitive and consummatory components of motivation were evaluated in adult C57BL/6JRj male mice experiencing chronic distress induced by oral corticosterone (CORT), using multiple complementary discrete behavioural tests. Behavioural data (from Novelty Supressed Feeding, operant effort-based choice, Free Feeding and Sucrose Preference tasks) collectively show that behavioural initiation, effort allocation and hedonic appreciation and valuation are altered in mice exposed to several weeks of oral CORT treatment. Additionally, data analysis from FosB immunohistochemical processing of postmortem brain samples highlight a CORT-dependent dampening of neural activation in the anterior insular cortex (aIC) and basolateral amygdala (BLA), key telencephalic brain regions involved in cue appetitive and consummatory motivational processing. Combined, these results suggest that chronic distress-induced irregular aIC and BLA neural activations with reduced effort production and attenuated reward value processing during reinforcement-based instrumental learning could result in maladaptive decision-making under uncertainty. The current study further illustrates how the stoichiometry of effort and reward processing contributes to dynamically adjust the motivational threshold triggering goal-directed behaviours in versatile environments.

neuroscience↗

bioRxiv2021

Your pleasure is mine; when people share amusical emotional experience during a livemusic performance in a concert hall.

Over the years, several publications have proposed that musical sound could be an ancestral emotional way of communication, thus positing an ancestral biological function for music. Understanding how musical emotions, and the pleasure derived from music regardless of the musical valence, can be shared between individuals is a fascinating question, and investigating it can shed light on the function of musical reward. Is the pleasure felt at the individual level transmitted on a collective level? And if so, how? We investigated these questions in a natural setting during an international competition for orchestra conductors. Participants (n=15) used a dedicated smartphone app to report their subjective emotional experiences in real time during a concert. We recorded participants electrodermal activity (EDA) and cerebral activity with electroencephalography (EEG). The overall behavioral real time ratings suggest a possible social influence on the reported and felt pleasure. The physically closer the participants, the more similar their reported pleasure. We estimated the inter-individual cerebral coherence, which indicates the degree of mutual cerebral information between pairs of participants in the frequency domain. The results show that when people simultaneously reported either high or low pleasure, their cerebral activities were closer than for simultaneous neutral pleasure reports. Participants skin conductance levels were also more coupled when reporting higher emotional degrees simultaneously. More importantly, the participants who were physically closer had higher cerebral coherence, but only when they simultaneously reported intense pleasure. We propose that mechanisms of emotional contagion and/or emotional resonance could explain why a form of emotional connecting force could arise between people.

neuroscience↗

bioRxiv2019

An artistic approach to neurofeedback for emotion regulation

Neurofeedback has been shown to be a promising tool for learning to regulate ones own emotions in healthy populations and in neuropsychiatric disorders. While it has been suggested that neurofeedback performance improves when sensory feedback is related to the pathology under consideration, it is still difficult to represent in real time a proper feedback representative of our emotional state. Since emotion is a central part of peoples dealings with artworks, we have initiated a collaboration between neuroscientists and artists to develop a visual representation of emotions that can be used in neurofeedback experiences. As a result of this collaboration, emotions were represented as particles, moving in a white sphere according to valence and arousal levels. In this study, several possibilities for particle control were explored: direction of particles, their concentration in a specific place, or their gravity. 107 participants evaluated these performances, either in laboratory condition or at various scientific and artistic events. At the end of the experiment, questionnaires were distributed to participants who were asked to indicate on scales ranging from 0 to 5 how artistic the different representations were and could be used as a clinical activity, whether they thought they had successfully controlled the particles during the neurofeedback exercise, and whether they had appreciated the experience. We found that influing on the direction and concentration of particles was considered the most artistic with an average score around 3/5. 47% of the participants considered the concentration of particles as artistic. In addition, although this is not the purpose of this study, we found that participants could significantly control the direction of particles during this session. These encouraging results constitute a first step before evaluating the effectiveness of our emotional neurofeedback over several sessions in healthy, then pathological populations.

neuroscience↗

bioRxiv2019

Modeling decision-making under uncertainty: a direct comparison study between human and mouse gambling data

Decision-making is a conserved evolutionary process enabling to choose one option among several alternatives, and relying on reward and cognitive control systems. The Iowa Gambling Task allows to assess human decision-making under uncertainty by presenting four cards decks with various cost-benefit probabilities. Participants seek to maximize their monetary gains by developing long-term optimal choice strategies. Animal versions have been adapted with nutritional rewards but interspecies data comparisons are still scarce. Our study directly compared physiological decision-making performances between humans and wild-type C57BL/6 mice. Human subjects fulfilled an electronic Iowa Gambling Task version while mice performed a maze-based adaptation with four arms baited in a probabilistic way. Our data show closely matching performances among species with similar patterns of choice behaviors. Moreover, both populations clustered into good, intermediate, and poor decision-making categories with similar proportions. Remarkably, mice good decision-makers behaved as humans of the same category, but slight differences among species have been evidenced for the other two subpopulations. Overall, our direct comparative study confirms the good face validity of the rodent gambling task. Extended behavioral characterization and pathological animal models should help strengthen its construct validity and disentangle determinants of decision-making in animals and humans.

neuroscience↗