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Good brain health plays a significant role in an individual's well-being and profoundly impacts the collective economy and society. Brain development does not stop at birth, and some aspects continue throughout childhood and adolescence, allowing the full development of cognitive functions. Different determinants related to physical health, healthy environments, safety and security, life-long learning and social connection as well as access to quality services influence the way our brains develop, adapt and respond to stress and adversity. Ongoing progress in neurobiology and cognitive neuroscience allows the design of better prevention and intervention strategies to help avoid brain deficits and/or limit their impact and maintain brain health. The European Brain Council (EBC) convened an expert meeting during the Federation of European Neuroscience Societies (FENS) Forum 2024 to address youth brain health challenges. In recent years, the importance of brain health has garnered significant attention across scientific, medical and policy-making communities. Although much focus has traditionally been on neurodegenerative conditions affecting the elderly, a paradigm shift towards prioritizing brain health in youth is both timely and necessary. This shift can profoundly impact individual lives and society, necessitating an interdisciplinary approach that brings neuroscience to the forefront of public health and informs evidence-based policy. The topic is of utmost importance as EBC launched this year a new campaign on No Health Without Brain Health rallying support with its member organizations and the wider brain community for the increased prioritization of brain health on EU health and research agendas., (© 2025 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Brain health is a pressing global concern. Poor diet quality is a recognized major environmental risk factor for brain disorders and one of the few that is modifiable. There is substantial evidence that nutrition impacts brain development and brain health across the life course. So why then is the full potential of nutrition not utilized to improve brain function? This commentary, which is based on discussions of the European Brain Research Area BRAINFOOD cluster, aims to highlight the most urgent research priorities concerning the evidence base in the area of nutrition and brain health and identifies 3 major issues that need to be addressed: (1) increase causal and mechanistic evidence on the link between nutrition and brain health, (2) produce effective messages/education concerning the role of food for brain health, and (3) provide funding to support collaborative working across diverse stakeholders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neurological conditions are the leading cause of death and disability combined. This public health crisis has become a global priority with the introduction of WHO's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP). 18 months after this plan was adopted, global neurology stakeholders, including representatives of the OneNeurology Partnership (a consortium uniting global neurology organisations), take stock and advocate for urgent acceleration of IGAP implementation. Drawing on lessons from relevant global health contexts, this Health Policy identifies two priority IGAP targets to expedite national delivery of the entire 10-year plan: namely, to update national policies and plans, and to create awareness campaigns and advocacy programmes for neurological conditions and brain health. To ensure rapid attainment of the identified priority targets, six strategic drivers are proposed: universal community awareness, integrated neurology approaches, intersectoral governance, regionally coordinated IGAP domestication, lived experience-informed policy making, and neurological mainstreaming (advocating to embed brain health into broader policy agendas). Contextualised with globally emerging IGAP-directed efforts and key considerations for intersectoral policy design, this novel framework provides actionable recommendations for policy makers and IGAP implementation partners. Timely, synergistic pursuit of the six drivers might aid WHO member states in cultivating public awareness and policy structures required for successful intersectoral roll-out of IGAP by 2031, paving the way towards brain health for all., Competing Interests: Declaration of interests DW is Chair (unpaid) and CC-B is Vice-Chair (unpaid) of the OneNeurology Partnership. CT has received grants or contracts from ERA-Net Neuron and AbbVie; consulting fees from AbbVie, Eli Lilly, Teva, Pfizer, Lundbeck, and Dompeé; payment or honoraria for lectures or presentations from AbbVie, Eli Lilly, Teva, Pfizer, and Lundbeck; travel support from AbbVie, Eli Lilly, and Lundbeck; and is past president of the International Headache Society. MTF has received consulting fees from Roche, payment or honoraria for lectures or presentations from Lundbeck, and is the co-founder of Women's Brain Project. KR has received consulting fees from Roche (Operetta trial), and payment or honoraria for lectures or presentations from Merck. BMK has received a grant from the National Institute on Aging; royalties or licences from Elsevier; payment or honoraria for lectures and presentations from the American Academy of Neurology, Parkinson's Foundation, International Parkinson and Movement Disorders Society, and Davis Phinney Foundation; and is President of the International Neuropalliative Care Society. CW is an employee of Meningitis Research Foundation, which has received grants from GlaxoSmithKline, Pfizer, Sanofi Pasteur, Serum Institute, and Tableau Foundation. PCZ has received consulting fees from Idorsia, CVS Caremark, Eisai, and Jazz Pharmaceuticals; has stock or stock options in Teva (spouse); and is President of the World Sleep Society. DWD has received consulting fees from Amgen, Atria, CapiThera, Cerecin, Ceruvia Lifesciences, CoolTech, Ctrl M, Allergan, AbbVie, Biohaven, GlaxoSmithKline, Lundbeck, Eli Lilly, Novartis, Impel, Satsuma, Theranica, WL Gore, Genentech, Nocira, Perfood, Praxis, AYYA Biosciences, Revance, Pfizer, and Perfood; payment or honoraria for lectures or presentations from American Academy of Neurology, Headache Cooperative of the Pacific, Canadian Headache Society, Canadian Pain Society, MF Med Ed Research, Biopharm Communications, CEA Group Holding Company (Clinical Education Alliance), Teva, Amgen, Eli Lilly, Lundbeck, Pfizer, Vector Psychometric Group, Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Academy for Continued Healthcare Learning, Majallin, Medlogix Communications, Medica Communications, MJH Lifesciences, Miller Medical Communications, WebMD Health/Medscape, Wolters Kluwer, Oxford University Press, and Cambridge University Press; has non-profit board membership with American Brain Foundation, American Migraine Foundation, OneNeurology, International Headache Society Global Patient Advocacy Coalition, Atria Health Collaborative, Arizona Brain Injury Alliance, and Domestic Violence HOPE Foundation/Panfila; has received financial support from the Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, and Patient Centered Outcomes Research Institute; has stock options in Aural Analytics, ExSano, Palion, Man and Science, Healint, Theranica, Second Opinion/Mobile Health, Epien, Nocira, Ontologics, King-Devick Technologies, EigenLyfe, AYYA Biosciences, Cephalgia Group, and Atria Health; has shares in Axon Theraputics, Ontologics, EigenLyfe, and Cephalgia Group; is on the board of directors for Axon Theraputics, King-Devick Technologies, and Cephalgia Group; and has the following patent (number 17189376.1-1466; Title: Onabotulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis (non-royalty bearing); patent application submitted: Synaquell (Precon Health). AH is an employee of Multiple Sclerosis International Federation (MSIF); MSIF received funding from BristolMyersSquibb, Sanofi, Merck, Viatris (formerly Mylan), Novartis, Biogen, and Roche over the last 5 years. MSIF's independence and all its donations from the health-care industry are governed by MSIF's health-care policy. MSIF has not received any funding from industry for its access to medicines work in 2019, 2020, 2021, 2022, or 2023. JL-D was an employee at MSIF until October, 2023. OG and TH received institutional support from the European Federation of Neurological Associations in running the OneNeurology Secretariat. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The stomach-derived octanoylated peptide ghrelin was discovered in 1999 and recognized as an endogenous agonist of the growth hormone secretagogue receptor (GHSR). Subsequently, ghrelin has been shown to play key roles in controlling not only growth hormone secretion, but also a variety of other physiological functions including, but not limited to, food intake, reward-related behaviors, glucose homeostasis and gastrointestinal tract motility. Importantly, a non-acylated form of ghrelin, desacyl-ghrelin, can also be detected in biological samples. Desacyl-ghrelin, however, does not bind to GHSR at physiological levels, and its physiological role has remained less well-characterized than that of ghrelin. Ghrelin and desacyl-ghrelin are currently referred to in the literature using many different terms, highlighting the need for a consistent nomenclature. The variability of terms used to designate ghrelin can lead not only to confusion, but also to miscommunication, especially for those who are less familiar with the ghrelin literature. Thus, we conducted a survey among experts who have contributed to the ghrelin literature aiming to identify whether a consensus may be reached. Based on the results of this consensus, we propose using the terms "ghrelin" and "desacyl-ghrelin" to refer to the hormone itself and its non-acylated form, respectively. Based on the results of this consensus, we further propose using the terms "GHSR" for the receptor, and "LEAP2" for liver-expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist., (© 2022 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Does it matter what we eat for our mental health? Accumulating data suggests that this may indeed be the case and that diet and nutrition are not only critical for human physiology and body composition, but also have significant effects on mood and mental wellbeing. While the determining factors of mental health are complex, increasing evidence indicates a strong association between a poor diet and the exacerbation of mood disorders, including anxiety and depression, as well as other neuropsychiatric conditions. There are common beliefs about the health effects of certain foods that are not supported by solid evidence and the scientific evidence demonstrating the unequivocal link between nutrition and mental health is only beginning to emerge. Current epidemiological data on nutrition and mental health do not provide information about causality or underlying mechanisms. Future studies should focus on elucidating mechanism. Randomized controlled trials should be of high quality, adequately powered and geared towards the advancement of knowledge from population-based observations towards personalized nutrition. Here, we provide an overview of the emerging field of nutritional psychiatry, exploring the scientific evidence exemplifying the importance of a well-balanced diet for mental health. We conclude that an experimental medicine approach and a mechanistic understanding is required to provide solid evidence on which future policies on diet and nutrition for mental health can be based., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Rats were exposed to free-choice diets (fat plus one of two different sugar solutions, glucose or sucrose), and the metabolic consequences and impact on locomotor activity and anxiety-like behavior were explored., Methods: For 3 weeks, 7-week-old male rats were offered either chow only or free-choice high-fat diets differing in their added sugar: no sugar, sucrose, or glucose. In a second experiment, after 2 weeks on the diets, rats were switched from high sucrose to high glucose for two additional weeks. Metabolic end points included body weight, food intake, food choice, glycemic control, metabolic hormones, fat pad weight, brown adipose tissue weight, and gene expression. Behavioral analysis included locomotor and anxiety-like activity in the open field and elevated plus maze., Results: Both sugar diets enhanced adiposity and induced hyperphagia, favoring unhealthier dietary selection above that of the control diets (chow or free-choice high-fat with no sugar). Despite isocaloric intake in the sugar-containing diets, offering glucose instead of sucrose was associated with improved insulin sensitivity. The sugar-containing diets reduced activity (but with movements of increased velocity) and induced an anxiety-like phenotype., Conclusions: Although free-choice diets negatively impacted on metabolism and anxiety-like behavior, replacing sucrose with glucose improved insulin sensitivity and may therefore be better for health., (© 2019 The Authors Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).)

Health nudge interventions to steer people into healthier lifestyles are increasingly applied by governments worldwide, and it is natural to look to such approaches to improve health by altering what people choose to eat. However, to produce policy recommendations that are likely to be effective, we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from the gastrointestinal tract and adipose tissue, which affect not only our hunger and satiety but also our motivation to eat particular nutrients, and the reward we experience from eating. Thus, to develop the evidence base necessary for effective policies, we need to build bridges across different levels of knowledge and understanding. This requires experimental models that can fill in the gaps in our understanding that are needed to inform policy, translational models that connect mechanistic understanding from laboratory studies to the real life human condition, and formal models that encapsulate scientific knowledge from diverse disciplines, and which embed understanding in a way that enables policy-relevant predictions to be made. Here we review recent developments in these areas.

Context: Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation., Objective: This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness., Intervention: In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined., Main Outcome Measures: In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011)., Conclusions: Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN.

A number of appetite-regulating gut hormones alter behaviors linked to reward, anxiety/mood, memory and cognitive function, although for some of these (notably GLP-1 and CCK) the endogenous signal may be CNS-derived. From a physiological perspective it seems likely that these hormones, whose secretion is altered by nutritional status and by bariatric weight loss surgery, orchestrate neurobiological effects that are integrated and linked to feeding/metabolic control. Consistent with a role in hunger and meal initiation, ghrelin increases motivated behavior for food and, when food is not readily available, decreases behaviors in anxiety tests that would otherwise hinder the animal from finding food. Of the many anorexigenic signals, GLP-1 and PYY have been linked to a suppressed reward function and CCK (and possibly GLP-1) to increased anxiety-like behavior., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The pleasure derived from eating may feel like a simple emotion, but the decision to eat, and perhaps more importantly what to eat, involves central pathways linking energy homeostasis and reward and their regulation by metabolic and endocrine factors. Evidence is mounting that modulation of the hedonic aspects of energy balance is under the control of peripheral neuropeptides conventionally associated with homeostatic appetite control. Here, we describe the significance of reward in feeding, the neural substrates underlying the reward pathway and their modification by peptides released into the circulation from peripheral tissues.

The incidence of obesity is increasing at an alarming rate and this worldwide epidemic represents a significant decrease in life span and quality of life of a large part of the affected population. Therefore an understanding of mechanisms underlying food overconsumption and obesity development is urgent and essential to find potential treatments. Research investigating mechanisms underlying obesity and the control of food intake has recently experienced a major shift in focus, from the brain's hypothalamus to additional important neural circuits controlling emotion, cognition and motivated behavior. Among them, the mesolimbic system, and the changes in reward and motivated behavior for food, emerge as new promising treatment targets. Furthermore, there is also growing appreciation of the impact of peripheral hormones that signal nutrition status to the mesolimbic areas, and especially the only known circulating orexigenic hormone, ghrelin. This review article provides a synthesis of recent evidence concerning the impact of manipulation of ghrelin and its receptor on models of food reward/food motivation behavior and the mesolimbic circuitry. Particular attention is given to the potential neurocircuitry and neurotransmitter systems downstream of ghrelin's effects on food reward., (Copyright © 2011. Published by Elsevier Inc.)

Here we review the emerging neurobiological understanding of the role of the brain's reward system in the regulation of body weight in health and in disease. Common obesity is characterized by the over-consumption of palatable/rewarding foods, reflecting an imbalance in the relative importance of hedonic versus homeostatic signals. The popular 'incentive salience theory' of food reward recognises not only a hedonic/pleasure component ('liking') but also an incentive motivation component ('wanting' or 'reward-seeking'). Central to the neurobiology of the reward mechanism is the mesoaccumbal dopamine system that confers incentive motivation not only for natural rewards such as food but also by artificial rewards (eg. addictive drugs). Indeed, this mesoaccumbal dopamine system receives and integrates information about the incentive (rewarding) value of foods with information about metabolic status. Problematic over-eating likely reflects a changing balance in the control exerted by hypothalamic versus reward circuits and/or it could reflect an allostatic shift in the hedonic set point for food reward. Certainly, for obesity to prevail, metabolic satiety signals such as leptin and insulin fail to regain control of appetitive brain networks, including those involved in food reward. On the other hand, metabolic control could reflect increased signalling by the stomach-derived orexigenic hormone, ghrelin. We have shown that ghrelin activates the mesoaccumbal dopamine system and that central ghrelin signalling is required for reward from both chemical drugs (eg alcohol) and also from palatable food. Future therapies for problematic over-eating and obesity may include drugs that interfere with incentive motivation, such as ghrelin antagonists.

Here we review recent advances that identify a role for the central ghrelin signalling system in reward from both natural rewards (such as food) and artificial rewards (that include alcohol and drugs of abuse). Whereas ghrelin emerged as a stomach-derived hormone involved in energy balance, hunger and meal initiation via hypothalamic circuits, it now seems clear that it also has a role in motivated reward-driven behaviours via activation of the so-called "cholinergic-dopaminergic reward link". This reward link comprises a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens together with a cholinergic input, arising primarily from the laterodorsal tegmental area. Ghrelin administration into the VTA or LDTg activates the "cholinergic-dopaminergic" reward link, suggesting that ghrelin may increase the incentive value of motivated behaviours such as reward-seeking behaviour ("wanting" or "incentive motivation"). Further, direct injection of ghrelin into the brain ventricles or into the VTA increases the consumption of rewarding foods as well as alcohol in mice and rats. Studies in rodents show beneficial effects of ghrelin receptor (GHS-R1A) antagonists to suppress the intake of palatable food, to reduce preference for caloric foods, to suppress food reward and motivated behaviour for food. They have also been shown to reduce alcohol consumption, suppress reward induced by alcohol, cocaine and amphetamine. Furthermore, variations in the GHS-R1A and pro-ghrelin genes have been associated with high alcohol consumption, smoking and increased weight gain in alcohol dependent individuals as well as with bulimia nervosa and obesity. Thus, the central ghrelin signalling system interfaces neurobiological circuits involved in reward from food as well as chemical drugs; agents that directly or indirectly suppress this system emerge as potential candidate drugs for suppressing problematic over-eating that leads to obesity as well as for the treatment of substance use disorder., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Recently we demonstrated that genetic or pharmacological suppression of the central ghrelin signaling system, involving the growth hormone secretagogue receptor 1A (GHS-R1A), lead to a reduced reward profile from alcohol. As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine., Results: We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist. Moreover, the ability of these drugs to condition a place preference was also attenuated by the GHS-R1A antagonist., Conclusions: Thus GHS-R1A appears to be required not only for alcohol-induced reward, but also for reward induced by psychostimulant drugs. Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.