Frontiers of Neurology and Neuroscience最新文献

Since its description in the 19th century, narcolepsy type 1 (NT1) has been considered as a model sleep disorder, and after the discovery of rapid eye movement (REM) sleep onset in the disorder, a gateway to understanding REM sleep. The discovery that NT1 is caused by hypocretin/orexin deficiency, together with neurochemical studies of this system, has helped to establish how this neuropeptide regulates the organization of sleep and wake in humans. Current analyses suggest that the main functions of the hypocretin/orexin system are (1) maintenance of wakefulness in the face of moderate sleep deprivation; (2) passive wake promotion, especially in the evening, driven by the circadian clock; (3) inhibition of REM sleep, with possible differential modulating effects on various subcomponents of the sleep-stage, explaining REM sleep dissociation events in NT1. Narcolepsy is also associated with an inability to consolidate sleep, a more complex phenotype that may result from secondary changes or be central to the role of hypocretin in coordinating the activity of other sleep- and wake-promoting systems. Novel technologies, such as the use of deep learning analysis of electroencephalographic signals, is revealing a complex pattern of sleep abnormalities in human narcolepsy that can be used diagnostically. The availability of novel devices measuring sleep 24 h per day also holds promise to provide new insights into how brain electrical activity and muscle tone are regulated by hypocretin.

During the last decade, optogenetic-based circuit mapping has become one of the most common approaches to systems neuroscience, and amassing studies have expanded our understanding of brain structures causally involved in the regulation of sleep-wake cycles. Recent imaging technologies enable the functional mapping of cellular activity, from population down to single-cell resolution, across a broad repertoire of behaviors and physiological processes, including sleep-wake states. This chapter summarizes experimental evidence implicating hypocretins/orexins, melanin-concentrating hormone, and inhibitory neurons from the lateral hypothalamus (LH) in forming an intricate network involved in regulating sleep and metabolism, including feeding behaviors. It further confirms the dual sleep-metabolic functions of LH cells, and sheds light on a possible mechanism underlying brain plasticity during sleep and metabolic disorders.

Orexins regulate a wide variety of biological functions, most notably the sleep-wake cycle, reward and stress processing, alertness, vigilance, and cognitive functioning. Alterations of central and peripheral orexin levels are linked to conditions such as narcolepsy, anorexia nervosa, age-related cognitive decline, and neurodegenerative disease. Preliminary studies suggest that orexin mimetics can safely promote the wake signal via orexin agonism during the day and that orexin receptor antagonists can promote the sleep signal during the night. Thus, novel orexin therapies have the potential to either improve memory, cognition, and daytime performance directly or indirectly, through promotion of good sleep. The full scope of the therapeutic potential of orexin therapies remains to be elucidated.

Studies of alexia and agraphia have played historically important roles in efforts to understand the relation between brain and behavior. In the second half of the 19th century, works by Paul Broca and Carl Wernicke led to the concept of delimited cortical centers in the left cerebral hemisphere concerned with discrete aspects of spoken and written language. These specialized centers were linked by white matter pathways. Charlton Bastian, Jean-Martin Charcot, Sigmund Exner, and Jules Dejerine championed center-pathway models of reading and writing. Dejerine played a dominant role, rejecting the idea of a left frontal lobe center that mediated writing and proposing a unique, specialized role for the left angular gyrus in both reading and writing. In 1891 and 1892, he detailed the symptoms of alexia and agraphia that resulted from injury to the left angular gyrus and from the isolation of the left angular gyrus from visual input required for reading. During the early 20th century, his work and that of other so-called diagram makers was confronted and largely discredited by Pierre Marie, joined later by Henry Head and Kurt Goldstein. In the 1960s, the center-pathway model was resurrected and refined by Norman Geschwind. He drew upon foundational works of Dejerine, Hugo Liepmann, and others to describe syndromes resulting from cortical disconnections and, in doing so, helped to establish a framework for the modern discipline of behavioral neurology.

The term dementia derives from the Latin root demens, which means being out of one's mind. Although the term "dementia" has been used since the 13th century, its mention in the medical community was reported in the 18th century. Even though the Greeks postulated a cerebral origin, the concept was not restricted to senile dementia and included all sorts of psychiatric and neurological conditions leading to psychosocial consequences. In the 19th century, individuals with dementia were recognized as patients, deserving medical care from specialists called alienists, and senile dementia became a medical disease. Subsequently, progresses in neuropathology allowed its fragmentation into different neuropathological conditions. Senile dementia was considered as a distinct entity from Alzheimer's seminal case published in 1906, and was first attributed to a vascular origin. However, from the late 1960s and for 20 subsequent years, Alzheimer's disease became the prototypical senile dementia. Only recently, the term dementia was abandoned for major neurocognitive disorder and the heterogeneity of the syndrome acknowledged again at the phenotypical and molecular levels. We hope a better understanding of this fascinating history will improve scientific research and impose humility towards the complex underpinnings of age-related cognitive decline.

Memory and forgetfulness have been viewed since antiquity from perspectives of physical, emotional, and spiritual states of well-being, and conceptualized philosophically. Numerous discussions of memory loss, or case reports, existed, but a fundamental advance in conceptualization of memory loss as a pathological clinical phenomenon originated when Sauvages classified "amnesia" as a medical disorder, in 1763. Originally, amnesia was recognized as a weakening or dissolution of memory, according to a taxonomy that ascribed known causes to the disorder. Etiologic factors included neurological disorders of stroke, hemorrhage, and head injury, metabolic dysregulation, alcohol and substance abuse, toxicity, anoxia, and other acute or chronic (sometimes progressive) brain disorders. Clinical descriptions of amnesia appeared internationally in medical dictionaries and scientific encyclopedias in the early 19th century. The possibility that amnesia could be either idiopathic, or symptomatic of another illness, was proposed based on the wide range of recognized etiologies and associations. Debate ensued regarding the status of amnesia as an illness or a symptom, but regardless, amnesia was soon recognized as an independent disorder of memory, distinguishable from disorders of global intellect, or of consciousness, or of language. Distinctions of amnesia considered its temporal gradient, duration and natural course, nature of onset, severity or depth of memory loss, course, and prognosis. Concepts of retrograde (forgetting knowledge preceding onset) and anterograde (difficulty learning, recalling new information) further specified the nature of amnestic memory difficulty. Alcoholic amnesia in Korsakoff's syndrome generated much attention. Amnesia as a clinical feature was critical to the development of notions of dissociation of conscious from subconscious recall in hysteria, and differentiation of neurogenically-based from psychogenically-based amnesia became central to understanding post-traumatic states. Amnesia studied as a disorder of memory remains an avenue to enrich clinical understanding of a condition that continues to be powerfully challenging to this day.

This chapter presents a historical overview of observations, instruments, and approaches in the area of neuropsychological assessment. In the 17th and 18th century literature dealing especially with language disorders following a brain disorder, one finds observations of physicians of striking dissociations of mental faculties that were impaired while others remained intact. Around the middle of the 19th century, neuropsychiatrists like Carl Wernicke began to develop procedures for assessing more specific components of mental functioning. German physicians, Conrad Rieger and Theodor Ziehen, seem to have developed the first neuropsychological test batteries. Kurt Goldstein, inspired by the rising Gestalt theory, argued that not the test score but the strategy used by a patient to perform a task is important. Alexander Luria also promoted an approach to assessment that was mainly based on subjective judgment. Studies on individual differences led to the development of an intelligence test battery by Alfred Binet. This battery was later transformed into the Army Alpha and Army Beta tests for selecting soldiers. Components of these intelligence tests have survived in the test kit of the modern neuropsychologist. This tradition also stimulated the development of psychometric analysis of tests. Two pioneers in the field of neuropsychological assessment were Shepherd Ivory Franz, favoring a clinical approach, and Ward Halstead, stimulating a strongly psychometric-based approach. The evaluation of language disorders has always been a specific area, requiring its own set of tests. The first comprehensive language battery was compiled by Bastian. Around the middle of the 20th century, when the localization of function approach had been rejected, neurologists preferred to examine language disorders clinically, using a battery that evaluated speech, comprehension, reading, and writing.

This chapter pays homage to the masters who made neuropsychology an esteemed and legitimate field in the 19th and 20th centuries. Here we offer a brief biography for each of them and an analysis of their discoveries: Théophile Alajouanine (1890-1980), Henry Charlton Bastian (1837-1915), Arthur L. Benton (1909-2006), Julian de Ajuriaguerra (1911-1993), Ennio De Renzi (1924-2016), Norman Geschwind (1926-1984), Kurt Goldstein (1878-1965), Henry Head (1861-1940), Henry Hécaen (1912-1983), Pierre Janet (1859-1947), François Lhermitte (1921-1998), Jean Lhermitte (1877-1959), Hugo Karl Liepmann (1863-1925), Heinrich Lissauer (1861-1891), Alexander Romanovich Luria (1902-1977), Brenda Milner (1918-), Théodule Ribot (1839-1916), Charles Richet (1850-1935), Paul Sollier (1861-1933), and Carl Wernicke (1848-1905).