This chapter describes the physiological correlates of hypnotizability associated with the morpho-functional aspects of the cerebellum and insula, which are brain structures neglected in physiological research on hypnoti...This chapter describes the physiological correlates of hypnotizability associated with the morpho-functional aspects of the cerebellum and insula, which are brain structures neglected in physiological research on hypnotizability. Both structures are involved in sensorimotor and interoceptive networks that play a cooperative role in sensorimotor and cognitive-emotional control. Hypnotizability-related cerebellar and insular characteristics may underlie observed differences in postural and visuomotor control, motor cortex excitability, functional equivalence between actual and imagined perception/action, detection and interpretation of bodily signals, emotional regulation, sense of agency, and body ownership. The reported findings highlight the relevance of mind-body interaction in everyday life and provide further insight into the complex networks involved in hypnotizability-related experience and behavior.
In this chapter, we propose to discuss the role of hypnosis and the combination of virtual reality and hypnosis (VRH) in emotional regulation as substantiated by clinical and neuroimaging evidence. The hypnotic process i...In this chapter, we propose to discuss the role of hypnosis and the combination of virtual reality and hypnosis (VRH) in emotional regulation as substantiated by clinical and neuroimaging evidence. The hypnotic process is characterised by focused attention, dissociation, and increased responsiveness to suggestions. This technique, related to the modulation of a large-scale neuronal network involved in emotional processing, could be drawn upon for treating psychological disorders in different clinical contexts, such as acute and chronic pain, oncology, anxiety disorders, phobias, and posttraumatic disorders. Neuroimaging studies focused on hypnosis have highlighted the specific modulation of the default mode, executive control, and salience networks, which play key roles in emotional processing and adaptive coping strategies. The chapter summarizes how hypnosis reshapes emotional experience and cognitive patterns by integrating clinical perspectives with neuroimaging data. It also discusses future directions, emphasising how VRH could change therapeutic practices, improving accessibility and outcomes for diverse populations.
Int Rev Neurobiol
· 2025 · PMID 41161944
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Placebo effects refer to changes in outcomes driven by learning and expectations, and they can shape responses to both pharmacologic and non-pharmacologic interventions. This chapter examines the neurobiology of placebo...Placebo effects refer to changes in outcomes driven by learning and expectations, and they can shape responses to both pharmacologic and non-pharmacologic interventions. This chapter examines the neurobiology of placebo and nocebo effects, with an emphasis on findings from human research. Drawing primarily from controlled laboratory studies, we highlight neuroimaging and transcriptomic mechanisms that shed light on the formation of placebo and nocebo responses. In particular, this chapter highlights how expectations and contextual cues can enhance or diminish the efficacy of both pharmacologic and non-pharmacologic interventions. A focus is placed on the role of open-label, cost perception, branding, and treatment modality in modulating placebo effects. The neurochemical basis of placebo analgesia is also examined, with a central role identified for endogenous opioids, and additional contributions from the endocannabinoid and dopaminergic systems. Neuroimaging studies reveal brain networks and structural markers that predict placebo responsiveness. Genetic and transcriptomic insights add a molecular layer to this understanding as well as RNA expression profiles, helping to identify placebo responders. Finally, the chapter emphasizes the clinical relevance of nocebo effects, detailing how negative expectations and communication can worsen outcomes. We also discuss the clinical relevance of these mechanisms, particularly in rheumatology, where both functional and structural brain changes have been observed. It advocates for improved communication strategies, personalized consent, and ethical integration of placebo science to optimize pain care and clinical trial designs. Future research should focus on translating individual variability in placebo and nocebo effects into strategies for advancing personalized and precision medicine.
Sleep is vital for physical and mental health and plays an important role in general well-being. Given the high prevalence of sleep disturbances in contemporary society, developing effective sleep-enhancing interventions...Sleep is vital for physical and mental health and plays an important role in general well-being. Given the high prevalence of sleep disturbances in contemporary society, developing effective sleep-enhancing interventions, including non-pharmacological approaches such as hypnosis, is important. In this chapter, we will first discuss the nature of sleep and the factors that can disturb it. We will present scientific evidence on how hypnotherapy can improve sleep parameters and disturbances. This will be followed by the presentation of experimental studies highlighting the potential of hypnotic suggestions to modulate objective parameters of sleep depth. In conclusion, we will hypothesise on a potential mechanism by which hypnotic suggestions might be capable of modulating sleep.
Hypnosis, a trance-like state marked by heightened suggestibility and focused attention, has shown substantial potential in affective neuroscience for influencing emotional processes and intuitive responses. Current rese...Hypnosis, a trance-like state marked by heightened suggestibility and focused attention, has shown substantial potential in affective neuroscience for influencing emotional processes and intuitive responses. Current research highlights hypnosis as an effective tool for stress reduction, with studies indicating that hypnotic interventions can reduce cortisol levels and autonomic stress responses, fostering relaxation and psychological resilience. Brain signals to monetary rewards indicate that hypnosis reduces impulsivity, which is important in substance abuse. A healthy lifestyle implies that we not only respond to immediate rewards but can also wait for delayed rewards. Hypnotic suggestions can make it easier to wait for delayed rewards. In dietary contexts, hypnosis has been used to alter food preferences, promoting healthier eating habits by modifying neural reward circuits associated with food choices, which could serve as a promising approach for weight management and nutrition improvement. Additionally, hypnosis has demonstrated efficacy in evoking feelings of safety and comfort, especially in high-stress environments like intensive care units (ICUs), where patients often experience anxiety and disorientation. By reinforcing perceived control and security, hypnosis can create a soothing, less intrusive ICU experience. The intersection of hypnosis and affective neuroscience offers valuable insights into the mind's capacity for self-regulation, with significant implications for therapeutic practices and mental health interventions. Future studies are encouraged to explore further the neurobiological mechanisms underlying hypnosis-induced affective changes to optimize and expand its applications.
Neutral hypnosis offers a valuable state for researchers interested in the nature of consciousness. By minimizing external influences and suggestions, it allows for the investigation of the intrinsic qualities of hypnoti...Neutral hypnosis offers a valuable state for researchers interested in the nature of consciousness. By minimizing external influences and suggestions, it allows for the investigation of the intrinsic qualities of hypnotic consciousness and its relationship to normal waking states. Studies have shown that neutral hypnosis can result in a significant shift in self-perception. Self-consciousness in neutral hypnosis is often characterized by distortions in the sense of self, fluctuations in self-awareness, and alterations in the experience of agency and body ownership. However, despite these clear effects, the field has largely overlooked the importance of these self-alterations, leading to a notable gap in the literature. In this chapter, we aim to address this gap by examining the existing research on self-consciousness in neutral hypnosis, emphasizing the need for more focused and well-structured studies utilizing the neurophenomenological methodology. Specifically, we propose to apply the neurophysiological three-dimensional model of complex experiential Selfhood, which conceptualizes the self as composed of three dynamically interacting aspects - first-person agency, embodiment, and narrative-reflection - each associated with three distinct sub-networks of the brain's self-referential network. These sub-networks are assessed through EEG operational synchrony analysis, providing a functional measure of their integration. Additionally, we outline several promising avenues for future research, accompanied by testable predictions regarding neurophenomenological alterations in Selfhood as a function of the depth of neutral hypnosis.
Therapies for myasthenia gravis (MG) include symptomatic and immunosuppressive/ immunomodulatory treatment. The application of one or more treatments should be based on known efficacy, particularly for specific disease s...Therapies for myasthenia gravis (MG) include symptomatic and immunosuppressive/ immunomodulatory treatment. The application of one or more treatments should be based on known efficacy, particularly for specific disease subtypes, disease activity, adverse effect profile, and patient co-morbidities. Traditional treatments include symptomatic treatment and disease- modifying therapy, such as steroids, immunosuppressants, plasmapheresis, intravenous immunoglobulin and thymectomy. Most patients are started with pyridostigmine and steroids but depending on severity or specific type of MG the immunosuppressant or other therapy are added. There is some variability in current recommendations in different MG management guidelines (e.g. Japanese compared to North American), mainly in the selection of glucocorticoids and the first-line non-steroidal immunosuppressants. In this chapter we carry out a review and comparison of all these treatments and compare the different international and national guidelines and consensus, and regional approaches. Approvals of novel therapeutics in MG should not deter clinicians from looking at older interventions, as these still play a key role in the treatment of MG.
The typical fluctuating skeletal muscle weakness in myasthenia gravis can make measuring disease severity challenging. Multiple measures have been developed to assess the signs and symptoms of myasthenia, from pure exami...The typical fluctuating skeletal muscle weakness in myasthenia gravis can make measuring disease severity challenging. Multiple measures have been developed to assess the signs and symptoms of myasthenia, from pure examination measures to fully patient-reported measures to combinations. There are also measures aimed at assessing quality of life and satisfaction. Electrophysiology and serology have also been used in some studies as surrogate outcomes. In this chapter, we review outcomes specifically developed to assess disease severity in myasthenia, as well as quality of life, and data on electrophysiology and serology as outcome measures.
Myasthenia Gravis (MG) often affects young women, in whom reproductive issues are of importance, including the possibility of MG exacerbation during pregnancy, potential obstetric risks in pregnancy and treatment-related...Myasthenia Gravis (MG) often affects young women, in whom reproductive issues are of importance, including the possibility of MG exacerbation during pregnancy, potential obstetric risks in pregnancy and treatment-related risks to the fetus. Apart from pregnancy, hormonal changes throughout a woman's lifespan may also affect MG symptoms. In this chapter, we discuss the role of sex hormones in MG and the disease burden in women. We also review the effects of pregnancy on MG, the evidence regarding pregnancy outcomes and current recommendations regarding MG treatments during pregnancy.
The diagnosis of myasthenia gravis (MG) is strongly considered in a patient complaining of fatigable weakness and in whom muscle fatigability is demonstrated during bedside examination. This chapter will be dedicated to...The diagnosis of myasthenia gravis (MG) is strongly considered in a patient complaining of fatigable weakness and in whom muscle fatigability is demonstrated during bedside examination. This chapter will be dedicated to the history-taking and clinical examination of patients with MG and we will also touch upon other myasthenic syndromes and mimics. Most patients first experience fatigable ocular symptoms. The symptoms may remain isolated to the eyes (ocular MG) or later involve the limb, bulbar or respiratory muscles (generalized MG). The examination of the myasthenic patient serves to demonstrate fatigability and distinguish this from non-specific central fatigue or lack of energy. This chapter presents a focused discussion by a neuro-ophthalmologist and neurologists, largely based on their clinical experience.
The diagnostic workup for myasthenia gravis extends beyond the objective evaluation of skeletal muscle fatigue during neurological examinations. It incorporates antibody testing, electrophysiological studies to confirm n...The diagnostic workup for myasthenia gravis extends beyond the objective evaluation of skeletal muscle fatigue during neurological examinations. It incorporates antibody testing, electrophysiological studies to confirm neuromuscular transmission impairment, and chest imaging to detect thymoma. Positive clinical response to acetylcholinesterase inhibitors may also support diagnosis. Key clinical assessments focus on symptoms of skeletal muscle fatigability, particularly in ocular, bulbar, and limb-girdle muscles. While the ice-pack test is commonly used to assess ptosis, the global availability of acetylcholinesterase inhibitors for testing remains limited. Radioimmunoassay is the most sensitive diagnostic method for MG-specific antibodies, such as AChR and MuSK, followed by cell-based assays that utilize clustered receptors. Enzyme-linked immunosorbent assay (ELISA) is another option, though with reduced specificity. Electrophysiological evaluation begins with repetitive nerve stimulation (RNS) to detect postsynaptic transmission failure, with single-fiber electromyography (SFEMG) employed in cases where RNS results are inconclusive. All patients with MG, regardless of subtype, should undergo chest imaging (CT or MRI) to screen for thymoma. Differential diagnoses to consider include congenital myasthenic syndromes, cranial nerve disorders such as Horner syndrome or third nerve palsy, autoimmune demyelinating polyneuropathy, mitochondrial myopathy, and motor neuron disorders.
The diagnostic precision of MG, along with the emergence of novel treatments targeting the autoimmune response, has ushered the field into a new era, moving MG management closer to personalized medicine. However, critica...The diagnostic precision of MG, along with the emergence of novel treatments targeting the autoimmune response, has ushered the field into a new era, moving MG management closer to personalized medicine. However, critical gaps remain, including the absence of approved treatments for seronegative MG, limited attention to Lambert-Eaton myasthenic syndrome and congenital myasthenic syndromes, and the need for more precise biomarkers. Current clinical trials primarily rely on outcomes that measure symptoms and/or muscle weakness/fatigability; however, there is a need for biomarkers that better reflect disease activity, enable early diagnosis in seronegative MG, and identify the underlying antibodies in these patients. Predictive biomarkers are also needed to assess the risk of generalization from ocular MG and the likelihood of relapses. Furthermore, despite their efficacy, novel treatments such as complement and FcRn inhibitors are costly and inaccessible in many countries. Future MG research must, therefore, prioritize socioeconomic considerations alongside therapeutic advancements. Also, a better understanding of the fatigue in MG, with differences in men and women, is essential to better design treatment over time.
The role of non-pharmacological management in MG is currently underdeveloped and underutilized. Exercise training has been shown to be both feasible and beneficial in improving function and strength in individuals with M...The role of non-pharmacological management in MG is currently underdeveloped and underutilized. Exercise training has been shown to be both feasible and beneficial in improving function and strength in individuals with MG. Observational studies indicate that physical activity is associated with reduced perceived fatigue. Barriers to exercise persist in MG, and should be addressed by healthcare professionals. Maintaining or increasing muscle strength and endurance as well as cardiorespiratory fitness should be prioritized regardless of current level of function. In the general population, exercise has the potential to reduce anxiety and depression although studies in MG are still lacking. Exercise programs should be individualized and progressive, with a clear emphasis on reducing sedentary behavior. Current research has primarily focused on individuals with mild-moderate MG. Further studies are needed to understand the potential impact of exercise training on enhancing pharmacological therapies and the potential role of exercise in immunomodulation in MG. This chapter reviews the existing literature on exercise in MG.
Treatment options for patients with myasthenia gravis (MG) are rapidly increasing. Seven new MG therapies across 2 novel classes have been approved by the FDA to treat MG; a robust treatment pipeline spans at least 7 nov...Treatment options for patients with myasthenia gravis (MG) are rapidly increasing. Seven new MG therapies across 2 novel classes have been approved by the FDA to treat MG; a robust treatment pipeline spans at least 7 novel therapeutic classes. International MG Consensus Guidance define successful treatments as those that result in minimal disease manifestations or remission with no more than minimal adverse events (AE). The MG community has a number of disease specific outcome measures to evaluate treatment response and patient quality of life. Treatment efficacy only represents one important way to assess treatment value; side effects, burden of therapy, and cost all reduce treatment value. Indeed, patients and clinicians both rate treatment safety as a key consideration when choosing among treatment options. Despite this concern, we have not established the best way to measure side effect burden in MG clinical trials or clinics. To date, the MG community has been focused on the negative side effects associated with corticosteroids, despite well documented, unique side effect profiles that are associated with both traditional and new generation non-steroid MG treatments, some of which can be serious and life threatening. Careful measurement of side effect burden and comparison of this burden among MG therapies will be critical as we attempt to optimize treatment for our patients. This chapter focuses on the importance of measuring MG treatment side effect burden and three measures that may facilitate measuring this burden in future comparative effectiveness trials and in the clinic.
Advances in immunology over the last several years have provided insights into the pathophysiology of autoimmune diseases such as generalized myasthenia gravis (gMG). This has translated into the development of effective...Advances in immunology over the last several years have provided insights into the pathophysiology of autoimmune diseases such as generalized myasthenia gravis (gMG). This has translated into the development of effective, rapidly acting, and targeted novel immune therapies. The two categories of new therapies available at present include the complement C5 inhibitors and the neonatal Fc receptor (FcRn) antagonists. The place of these drugs in the algorithm of MG treatment continues to evolve. Simultaneously, drug development proceeds, with other complement inhibitors, new B cell inhibitor therapy, chimeric antigen therapies and immune tolerizing therapies are in the pipeline. The treatment of gMG will continue to evolve; treatments for subgroups of patients including MuSK- ab+, seronegative and thymoma-associated MG are important areas for future development.
Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness due to impaired neuromuscular transmission. Despite therapeutic advances, acute exacerbations and myasthenic crises rem...Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness due to impaired neuromuscular transmission. Despite therapeutic advances, acute exacerbations and myasthenic crises remain significant challenges. This chapter offers an in-depth overview of rescue therapies for MG, detailing the mechanisms, efficacy, and safety of established treatments such as IVIG and PLEX, and discussing the potential of novel therapies like eculizumab and efgartigimod in acute MG management. We emphasize the importance of personalized treatment approaches tailored to factors such as antibody status, disease severity, and comorbidities. Strategies for monitoring treatment response and managing complications are also discussed. By synthesizing current evidence and expert recommendations, this chapter aims to equip clinicians with the knowledge needed to optimize rescue therapy in MG, ultimately improving outcomes during acute exacerbations and crises.
Myasthenia gravis (MG) is the prototypical disorder of the neuromuscular junction. The clinical hallmarks of MG are fatigability and fluctuating voluntary muscle weakness. Although MG can potentially affect any muscle, s...Myasthenia gravis (MG) is the prototypical disorder of the neuromuscular junction. The clinical hallmarks of MG are fatigability and fluctuating voluntary muscle weakness. Although MG can potentially affect any muscle, some muscle groups are involved preferentially and an important clinical distinction can be made between the disease localized exclusively to the extraocular muscles and the disease affecting other muscle groups, called "generalized", with relevant therapeutic and prognostic implications. The clinician should be familiar with both common and uncommon patterns of weakness associated with MG and actively search for suggestive anamnestic cues when this disease is suspected. This chapter will focus on the different clinical presentations of MG, encompassing both the detailed clinical complaints and the anamnestic aspects, with a focus on the specific muscular distribution, and the clinical features associated with myasthenic crisis. Lastly, the most described atypical presentations and their differential diagnostic work-up will be reviewed.
Autoimmune Myasthenia Gravis (MG) is a disease characterized by fatigable muscle weakness and autoantibodies. It can be divided by the presence of serum autoantibodies into two major categories where Immunoglobulin G (Ig...Autoimmune Myasthenia Gravis (MG) is a disease characterized by fatigable muscle weakness and autoantibodies. It can be divided by the presence of serum autoantibodies into two major categories where Immunoglobulin G (IgG) against either the acetylcholine receptor (AChR), or muscle specific kinase (MuSK) causes fatigable muscle weakness. The clinical relevance of Low-density lipoprotein-receptor related protein-4 IgG (LRP4) is debated. These antibodies disrupt neuromuscular transmission via different mechanisms: AChR antibodies, mostly of IgG1 and IgG3 subclass, can activate complement leading to a simplification of the NMJ architecture, block acetylcholine binding to its receptor to prevent channel opening, and internalize AChR. By contrast, MuSK antibodies, mostly of the IgG4 subclass, impair MuSK-LRP4 interactions, and LRP4 antibodies may interfere with agrin-induced clustering. Once these antibody targets were identified the development of antibody assays began. Patrick and Lindstrom made the landmark discovery that antibodies against soluble AChR caused acute flaccid paralysis in immunized rabbits which kickstarted test development. The first, and until recently, most useful test was the radioimmunoassay (RIA) where AChR radiolabeled with toxin from venomous snakes allowed quantitative measurement of AChR-IgG. Most recently the clustered AChR cell-based assays (CBA) provide a significant improvement in test sensitivity over all other methods. MuSK assays followed a similar but shorter path. The accurate detection of AChR and MuSK antibodies has a crucial role in supporting the clinical diagnosis and management of MG which includes a diverse population of patients with a wide range of clinical manifestations, disease severity and response to standard and new therapies. In this chapter we highlight how distinct target-specific IgG autoantibodies cause neuromuscular transmission defects, and subsequently shape disease manifestations in the different MG antibody subgroups. We review the evolution of diagnostic assays, from early RIA to modern CBA, and addresses interpretative pitfalls, particularly in borderline or "seronegative" cases. Finally, the authors address the significance of accurate autoantibody detection in the diagnosis and management of patients with one of the antibody MG subtypes, as well as in patients with other autoimmune conditions and thymic malignancies.