{"title":"Neuroscience of coma.","authors":"Abid Y Qureshi, Robert D Stevens","doi":"10.1016/B978-0-443-13408-1.00010-5","DOIUrl":"https://doi.org/10.1016/B978-0-443-13408-1.00010-5","url":null,"abstract":"<p><p>Coma and disorders of consciousness are frequently considered in terms of two linked anatomic-functional systems: the arousal system and the awareness system. The mesopontine tegmentum (namely the cuneiform/subcuneiform nuclei of the caudal midbrain and the pontis oralis nucleus of the rostral pons) and the monoamine nuclei generate signals of arousal. These signals are augmented in lateral hypothalamus and basal forebrain, which then project to the thalamus and diffusely across the cortex. The medial dorsal tegmental tract is the main conduit for the ascending arousal system to directly activate the thalamic intralaminar nuclei and modulate thalamocortical networks, while the lateral dorsal tegmental tract connects to the thalamic reticular nucleus for regulation of intrathalamic inhibitory networks. The central thalamus (particularly the intralaminar nuclei) and the mesocircuit regulate the arousal system. Lesions to any part of this system, particularly paramedian and bilateral lesions, result in a depressed level of arousal. Distinct from the arousal pathways, the awareness system runs continuously as a stream of consciousness. It consists of large-scale distributed cortical networks that are necessary for representations of the external (executive control network with the dorsal/ventral attention networks) and the internal world (executive control network in conjunction with the default network). A feature of the awareness system is that it does not capture external and internal worlds at once and instead, holds singular representations, serially moment-by-moment. The medial dorsal nucleus of the thalamus serves as the associative nuclei of the default network, and the thalamic reticular nucleus regulates the awareness system. Lesions that disrupt large-scale networks, particularly nodes of cortical hubs, result in lack of awareness. Integrative paradigms such as the integrated information theory and the global neuronal workspace models are attempts to bind awareness and arousal into a unified experience of consciousness.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"207 ","pages":"29-47"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie M Vitello, Steven Laureys, Aurore Thibaut, Olivia Gosseries
{"title":"Non-pharmacologic interventions in disorders of consciousness.","authors":"Marie M Vitello, Steven Laureys, Aurore Thibaut, Olivia Gosseries","doi":"10.1016/B978-0-443-13408-1.00007-5","DOIUrl":"https://doi.org/10.1016/B978-0-443-13408-1.00007-5","url":null,"abstract":"<p><p>Severely brain-injured patients with disorders of consciousness pose significant challenges in terms of management, particularly due to the limited therapeutic options available. Despite the potential for some patients to benefit from interventions even years after the injury, clinicians often lack clear and reliable treatment strategies to promote patient recovery. In response to this clinical need, the field of neuromodulation has emerged as a promising alternative to traditional pharmacologic therapies. Both invasive and noninvasive brain stimulation techniques offer diverse possibilities for restoring physiologic neural activity and enhancing functional network integrity in these complex neurological disorders. This chapter offers a comprehensive overview of current neuromodulation techniques, exploring their potential applications and analyzing the existing evidence for their efficacy. Specifically, we describe transcranial electrical stimulation, transcranial magnetic stimulation, deep brain stimulation, low-intensity focused ultrasound, vagal nerve stimulation (including transcutaneous methods), spinal cord stimulation, and median nerve stimulation. While certain approaches show promise for patients with disorders of consciousness, there remains a pressing need for large-scale interventional clinical trials that will play an essential role for elucidating the underlying mechanisms of recovery and for refining stimulation parameters. This, together with the development of tailored individual interventions will move the field forward and optimize therapeutic outcomes.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"207 ","pages":"197-216"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evoked potentials in patients with disorders of consciousness.","authors":"Christoph Leithner, Christian Endisch","doi":"10.1016/B978-0-443-13408-1.00002-6","DOIUrl":"https://doi.org/10.1016/B978-0-443-13408-1.00002-6","url":null,"abstract":"<p><p>Acute coma in the intensive care unit and persistent disorders of consciousness (DoC) in neuro-rehabilitation are frequent in patients with hypoxic-ischemic encephalopathy after cardiac arrest (CA), traumatic brain injury, intracranial hemorrhage, or ischemic stroke. Reliable prognostication of long-term neurologic outcomes cannot be made by clinical examination alone in the early phase for many patients, and thus, additional investigations are necessary. Evoked potentials provide inexpensive, real-time, high temporal resolution, bedside, quantifiable information on different sensory pathways into the brain including local and global cortical processing. Short-latency somatosensory evoked potentials can reliably predict poor neurologic long-term outcome in the early phase after CA and are recommended by guidelines as one investigation within an early multimodal assessment. Middle-latency and event-related or cognitive evoked potentials provide information on the integrity of more advanced cortical processing, some closely related to consciousness. This information can help to identify those comatose patients with a good prognosis in the acute phase and help to better understand their precise clinical state and the chances of further recovery in patients with persistent DoC in neuro-rehabilitation. Further studies are necessary to improve the applicability of research findings in the clinical sphere.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"207 ","pages":"147-164"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advanced sleep phase syndrome: Role of genetics and aging.","authors":"Rosalia Silvestri, Biancamaria Guarnieri","doi":"10.1016/B978-0-323-90918-1.00005-8","DOIUrl":"https://doi.org/10.1016/B978-0-323-90918-1.00005-8","url":null,"abstract":"<p><p>Advanced sleep phase (ASP) is seldom brought to medical attention because many individuals easily adapt to their early chronotype, especially if it emerges before the age of 30 and is present in a first-degree relative. In this case, the disorder is considered familial (FASP) and is mostly discovered coincidentally in the presence of other sleep disorders, mainly obstructive sleep apnea syndrome (OSAS). The prevalence of FASP is currently estimated to be between 0.21% and 0.5%. Autosomal dominant mutations in circadian clock genes like PER2, CK1, PER3, CRY2, TIMELESS, and DEC2 have been linked to FASP, some with pleiotropic effects influencing other health aspects like migraine and depression. Early morning awakening is, instead, more common among older individuals, occurring in almost 4% of cases, without considering associated comorbidities. Advanced sleep-wake phase disorder (ASWPD) is characterized by a consistent and distressing anticipation of sleep-wake timing, affecting almost 1% of middle-aged individuals. On average, women have a shorter circadian period than men, making them more susceptible to ASWPD, albeit no significant gender discrepancies have been observed. Age-related alterations in circadian rhythms are exacerbated and compounded by neurodegenerative disorders, impacting the suprachiasmatic nucleus (SCN), sensitivity to light, and light responsiveness in those affected. Conflicting data has surfaced regarding the protective or detrimental effects of ASWPD in studies on aging, mild cognitive impairment (MCI), and diverse dementia conditions.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"206 ","pages":"61-70"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Antonia Quera-Salva, Sarah Hartley, Karol Uscamaita
{"title":"Circadian rhythm disorders in the blind.","authors":"Maria Antonia Quera-Salva, Sarah Hartley, Karol Uscamaita","doi":"10.1016/B978-0-323-90918-1.00007-1","DOIUrl":"https://doi.org/10.1016/B978-0-323-90918-1.00007-1","url":null,"abstract":"<p><p>Non-24-h sleep-wake disorder in blind patients without light perception is an orphan circadian rhythm sleep-wake disorder and is extremely rare in sighted people. Non-24-h sleep-wake disorder is characterized by insomnia and daytime sleepiness alternating with asymptomatic episodes. The frequency of symptomatic periods depends on the daily desynchronization of endogenous circadian pattern of each patient. Diagnosis requires anamnesis, a sleep diary, and actigraphy, if possible; in addition, repeated 24-h measures of circadian markers such as melatonin secretion are also required. Treatment consists of sleep hygiene, behavioral therapy, and melatonin/melatonin agonist administration. Melatonin treatment should start when the circadian rhythm of the patient is in phase with the solar cycle. Efficacy of treatment may be evident after weeks even months from the beginning. There is often a relapse when the medication is stopped.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"206 ","pages":"113-123"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sleep and circadian rhythms modeling: From hypothalamic regulatory networks to cortical dynamics and behavior.","authors":"Svetlana Postnova, Paula Sanz-Leon","doi":"10.1016/B978-0-323-90918-1.00013-7","DOIUrl":"https://doi.org/10.1016/B978-0-323-90918-1.00013-7","url":null,"abstract":"<p><p>Sleep and circadian rhythms are regulated by dynamic physiologic processes that operate across multiple spatial and temporal scales. These include, but are not limited to, genetic oscillators, clearance of waste products from the brain, dynamic interplay among brain regions, and propagation of local dynamics across the cortex. The combination of these processes, modulated by environmental cues, such as light-dark cycles and work schedules, represents a complex multiscale system that regulates sleep-wake cycles and brain dynamics. Physiology-based mathematical models have successfully explained the mechanisms underpinning dynamics at specific scales and are a useful tool to investigate interactions across multiple scales. They can help answer questions such as how do electroencephalographic (EEG) features relate to subthalamic neuron activity? Or how are local cortical dynamics regulated by the homeostatic and circadian mechanisms? In this chapter, we review two types of models that are well-positioned to consider such interactions. Part I of the chapter focuses on the subthalamic sleep regulatory networks and a model of arousal dynamics capable of predicting sleep, circadian rhythms, and cognitive outputs. Part II presents a model of corticothalamic circuits, capable of predicting spatial and temporal EEG features. We then discuss existing approaches and unsolved challenges in developing unified multiscale models.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"206 ","pages":"37-58"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Circadian pattern in restless legs syndrome.","authors":"Ambra Stefani","doi":"10.1016/B978-0-323-90918-1.00009-5","DOIUrl":"https://doi.org/10.1016/B978-0-323-90918-1.00009-5","url":null,"abstract":"<p><p>This chapter provides an overview of circadian pattern in restless legs syndrome (RLS). Circadian variation of symptoms is a known feature of RLS. According to one of the five essential criteria for RLS diagnosis, symptoms \"only occur or are worse in the evening or at night than during the day.\" RLS symptoms are most pronounced in the evening and at night, with a relative improvement in the late sleep period or in the early morning. This unique feature helps differentiating RLS from other movement disorders. Although differentiating the circadian pattern of RLS manifestations from the worsening of RLS symptoms at rest is not always easy, the independency of these two features has been demonstrated in several studies. Mechanisms implicated in circadian variations of RLS include dopamine, iron, opioids, and genetic factors, which all interact with each other. Further insights on circadian fluctuations in patients with RLS derive from clinical studies reporting circadian variations in sensory processing and spinal excitability, as well as from studies showing circadian variations in cortical excitability, default mode network, and cognition in patients with RLS.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"206 ","pages":"105-111"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alice Laurenge, Luis Jaime Castro-Vega, Gilles Huberfeld
{"title":"Reciprocal interactions between glioma and tissue-resident cells fueling tumor progression.","authors":"Alice Laurenge, Luis Jaime Castro-Vega, Gilles Huberfeld","doi":"10.1016/B978-0-443-19102-2.00007-7","DOIUrl":"https://doi.org/10.1016/B978-0-443-19102-2.00007-7","url":null,"abstract":"<p><p>Gliomas are the most frequent primary brain tumor and are essentially incurable. While nondiffuse gliomas are circumscribed, diffuse gliomas display an aggressive behavior characterized by tumor cell migration over large distances into the brain parenchyma, thereby precluding curative surgical resection. Almost all diffuse gliomas progress and recur as higher grades and become resistant to standard-of-care treatments. It is being increasingly recognized that glioma cells establish functional interactions with cells residing in the tumor microenvironment. Of these, tumor-associated microglia and macrophages (TAMs) play critical roles in immunosuppression through modulation of the extracellular matrix, and the secretion of molecules such as cytokines, neurotrophic factors, and micro-RNAs (miRNAs). Conversely, glioma cell signals influence cell states and drive the metabolic reprogramming of TAMs. Similarly, emergent evidence indicates that neuronal activity influences glioma by released factors and by establishing functional synapses with glioma cells to promote tumor growth and invasion. Glioma cells also affect local neuronal activities and maintain connections through microtube gap junctions to amplify local effects. Here, we discuss the molecular mechanisms underlying bidirectional interactions between glioma cells and TAMs, as well as between glioma cells and neurons. A better understanding of these cellular cross talks is crucial for the development of novel therapeutic strategies for diffuse gliomas.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"210 ","pages":"177-190"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hemispheric asymmetries in the control of upper limb movements.","authors":"Luigi Trojano","doi":"10.1016/B978-0-443-15646-5.00024-5","DOIUrl":"https://doi.org/10.1016/B978-0-443-15646-5.00024-5","url":null,"abstract":"<p><p>This chapter deals with the unique human abilities of using tools, imitating others' gestures, drawing, and building complex items. Herein, after a brief overview of clinical manifestations and assessment of disorders of tool use and imitation (upper limb apraxia) and of the impairments in drawing and assembling multipart objects (constructional apraxia), brain asymmetries are discussed mainly starting from the neuropsychologic studies on patients with focal brain lesions, although both upper limb apraxia and constructional apraxia are often observed during the course of neurodegenerative diseases. Although no room is allowed here for a full discussion of brain-behavior relationships, relevant functional neuroimaging findings in healthy individuals are considered. The data presented in this chapter clearly demonstrate that tool use, gesture imitation, and \"formative\" activities (i.e., drawing and assembling) require the interplay of several brain areas and neural networks distributed over both hemispheres. Nonetheless, gesture processing exhibits a quite strong lateralization to the left hemisphere in typical right-handers. As regards \"formative\" activities, the neural networks in both hemispheres seem to provide complementary contributions, although the left inferior parietal lobule might play a specific role. The convergence of gesture processing and \"formative activities\" in the parietal lobes might be related to their considerable expansion in our species and could suggest that some shared basic, still unknown, computational processes allowed the development of these skills in modern humans.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"208 ","pages":"393-405"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cerebellar asymmetries.","authors":"Caroline Nettekoven, Jörn Diedrichsen","doi":"10.1016/B978-0-443-15646-5.00005-1","DOIUrl":"https://doi.org/10.1016/B978-0-443-15646-5.00005-1","url":null,"abstract":"<p><p>The cerebellum is a subcortical structure tucked underneath the cerebrum that contains the majority of neurons in the brain, despite its small size. While it has received less attention in the study of brain asymmetries than the cerebrum, structural asymmetries in the cerebellum have been found in cerebellar volume that mirror cerebral asymmetries. Larger cerebellar structures have been reported on the right compared to the left, either for the whole cerebellar hemisphere or the anterior part of the cerebellum, with the latter accompanied by a left increase in the posterior cerebellum. Cerebellar asymmetries are considered evolutionary recent and have been observed prenatally and in early development. Both asymmetries in anterior-posterior divisions and specific lobules have been linked to handedness and cognitive abilities, in particular language. Functional lateralization in the cerebellum varies across motor and cognitive functions, with language activation predominantly localized in the right hemisphere, contralateral to cerebral activation. Meanwhile, working memory and executive functions are not lateralized to one hemisphere. New neuroimaging methods and resources, including a symmetric functional atlas of the cerebellum that enables precision mapping, open novel avenues for exploring cerebellar asymmetries and answering questions about the developmental timeline, relationships to behavior, and clinical relevance.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"208 ","pages":"369-378"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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