Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Although striking motor features characterize PD (e.g., bradykinesia, resting tremor, and rigidity), numerous nonmotor symptoms often precede motor symptoms. Sleep disturbances are observed in 60%–90% of patients with PD, impacting their quality of life. Sleep disturbances are influenced by many clinical factors, including disease-related neurodegeneration, nocturnal motor/nonmotor symptoms, medications, coexisting sleep disorders, aging, and other complications. Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream-enacting behavior and loss of normal atonia during REM sleep. The sublaterodorsal tegmental nucleus and ventromedial medulla oblongata, which play an important role in generating muscle atonia during REM sleep, are considered to have degenerated in patients with RBD. Isolated RBD is a strong risk factor for predicting future phenoconversion to neurodegenerative diseases, especially synucleinopathies. Patients with PD complicated by RBD may exhibit distinct clinical presentations compared to those without RBD. Various autonomic symptoms often precede motor symptoms in PD, and Lewy body pathology is observed in the central and peripheral autonomic nervous systems. The severity of autonomic symptoms may affect the subsequent outcomes of PD. This review outlines sleep disturbances and autonomic symptoms in PD.

The brainstem of mammals contains cranial motor nuclei composed of parasympathetic preganglionic neurons, which are distinct from the branchiomotor nuclei. In fish and amphibians, on the other hand, cranial preganglionic neurons form motor nuclei integrated with motor neurons innervating gill and branchiomotor muscles, and various tendencies for differentiation are observed within the nuclei. Reptilian and avian preganglionic neurons, as in mammals, separate from the branchiomotor nuclei to form the dorsal motor nucleus of the vagus and the salivary nuclei. The sympathetic preganglionic neurons in mammals are mediolaterally segregated to form multiple nuclei in the intermediate zone of the spinal cord. In other vertebrates, preganglionic neurons also form nuclei in the intermediate zone, but the main nucleus is located in the lateral region in amphibians, the medial region in teleosts and avians, and the intermediate region in reptiles.

The hypothalamus receives various types of stress information from the outside world through the prefrontal cortex, limbic system, and other cerebral networks. The autonomic neural network of the brainstem and spinal cord consists of the descending autonomic pathways from the hypothalamus to the preganglionic autonomic neurons and the ascending autonomic pathways carrying afferent information from visceral organs. In this paper, we define the hypothalamus and the cerebral neural network projecting to the hypothalamus as the upper part of the central autonomic network (CAN) and the autonomic neural network of the brainstem and spinal cord as the lower part of the CAN, and surveyed the literature for findings on decussation (neural crossing) of the CAN. The ascending autonomic pathways carrying afferent information from visceral organs cross at the level of the spinal cord. The descending sympathetic pathways from the hypothalamus to the lateral horns of the spinal cord cross in part at the level of the midbrain. The sympathetic descending tracts of the thermotropic sweat-accelerating pathway cross at the medullary-spinal cord transition zone and at the level of the spinal cord. According to clinical reports of hemiplegic patients with unilateral cerebral stroke, impairment of skin temperature and sweating is observed in the limbs contralateral to stroke lesions. Thus, the descending autonomic pathways involved in thermogenic sweating are presumed to cross at any level of the brainstem or spinal cord. The mystery of whether there is decussation in the central control circuits of the autonomic nervous system is a remaining frontier.

The "fight or flight" response (hereafter referred to as “this response”) is a universal behavioral response of all vertebrates and is evolutionarily well conserved. When the acute stress response (stress defense response) is triggered, the defense area of the hypothalamus becomes a command post that simultaneously switches on this response. The molecular mechanism involved in this response is as follows. Orexin, produced by the lateral hypothalamus, is the substance responsible for simultaneous activation of the circulatory and respiratory systems and analgesia. Osteocalcin, a protein that makes up 25% of bone, induces an acute stress response. Mitochondrial calcium single transporters in the mitochondrial inner membrane are responsible for transporting calcium ions, and are involved in increased heart rate. Neural circuits in the habenula-nucleus accumbens control behavioral choices in this response. The multidimensional control mechanism of the hypothalamus is assumed to consist of a very simple two-pole system: the emergency type and the normal type. The control mode of the stress response can be represented by a two-dimensional portfolio consisting of two intersecting axes: the neural information transfer system control axis and the heat energy system control axis. This response might reflect a pattern of emergency-type hypothalamic activity with extreme sympathetic dominance and extreme thermal energy expenditure dominance. ATP receptors are widely expressed in the hypothalamus and likely involve purinergic neurotransmission in the hypothalamus in this response. Stress intolerance is a condition in which endurance to stress is not demonstrated to the expected level, resulting in poor physical health.

Lewy-prone neurons are characterized by hyperbranching axons, which innervate to wide areas of brain and body, leading to generalized, poorly somatotopic clinical manifestations such αS mood, motivation, sleep, cognition and autonomic functions. Because αS is enriched in axon terminals, hyperbranching axons provide a heavy αS load to these neurons. Because MIBG is accumulated at axon terminals of cardiac sympathetic nerves, decreased myocardial uptake of MIBG is correlated with degeneration of cardiac sympathetic nerve, induced by αS deposition. Although lower brainstem is rich in αS deposits, upward spread of αS is not consistent. Rather, haphazard development of αS deposits, as multifocal Lewy-body disease may be more plausible. Moreover, decreased myocardial uptake of MIBG may happen even in the absence of Lewy pathology. Although decreased myocardial uptake of MIBG may suggest Lewy pathology, it is time to reconsider this convenient but oversimplified paradigm so that diagnostic accuracy is maximized by referencing to pathology obtained at autopsy.

Lower urinary tract dysfunction and sexual dysfunction are common in the patients with neurological disease. Lower urinary tract symptom is consisted of storage symptom and voiding symptom. History taking and using questionnaire are important and useful to detect lower urinary tract symptom and its cause. Bladder diary (frequency volume chart) and measurement of residual urine are also useful to evaluate lower urinary tract dysfunction and its cause. To detect sexual dysfunction, careful history taking and using questionnaire are also useful to understand. Each dysfunction is cause of decrease in quality of life. And restrictions on social activities and mental burden also occur. Therefore, it is necessary to understand and treat each dysfunction appropriately.

Osteoporosis, frequent urination, and dysphagia, which are increased in the late elderly, are associated with a decline in the level of activities of daily living. Analysis, evaluation, and control of the autonomic nervous system functions that support daily living will lead to development of effective tools to maintain the health of the elderly. We have been studying the mechanisms of somato-autonomic reflexes associated with activities of daily living. We have found that gentle stimulation of the skin, contraction of skeletal muscles, and mechanical stimulation of pharyngeal mucosa, modulates autonomic nervous system activity via somatosensory nerves, thereby modulating cardiovascular, endocrine, and skeletal muscle functions. In this paper, we would like to introduce our recent findings on somato-autonomic reflex mechanisms and discuss their application to the medical and nursing care of the elderly.

In the visual organs, parasympathetic innervation causes pupillary constriction, ciliary muscle constriction, increased choroidal blood flow, and lacrimal secretion. These responses are mediated by acetylcholine (ACh) M3 receptors, nitric oxide (NO), and vasoactive intestinal peptide (VIP). Sympathetic innervation causes pupillary dilation, decreased choroidal blood flow, and mild tear secretion via alpha receptors. In the olfactory organs, parasympathetic innervation promotes mucus secretion and increases mucosal blood flow. Sympathetic innervation is involved in decreasing mucosal blood flow. In olfactory cells, both parasympathetic and sympathetic nerves have been suggested to enhance odor responses. The odor-induced increased blood flow in the olfactory bulb is enhanced by activation of α4β2 nicotinic ACh receptors.

Emotions affect bodily functions such as heart rate and body temperature through changes in the activity of the autonomic nervous system. We empirically know that positive emotion is good for mental and physical health. I introduce here a method to evaluate positive emotion by measuring the behavioral outcome to understand possible brain mechanisms of such an affirmative effect of positive emotion on our body. I also introduce here the preliminary results from our research.

Transthyretin related hereditary amyloidosis (ATTRv amyloidosis) is caused by a genetic mutation in TTR gene and a systemic amyloidosis with organ dysfunction induced by amyloid deposition in peripheral nerves, cardiac tissues, gastrointestinal tracts, kidney, ocular tissues and autonomic nervous system. In many cases, small fiber neuropathy, orthostatic hypotension, sweating disorder, abnormal gastrointestinal movement, and erectile dysfunction are found from the early stage of the disease. Recently, since TTR tetrameric stabilizers, and gene silencing therapy have been developed for ATTRv, early diagnosis is very important. We have developed various examination methods for autonomic dysfunction at the early stage of ATTRv amyloidosis patients.