Reticular Activating System Research Articles

Effect of touch on proprioception: non-invasive trigeminal nerve stimulation suggests general arousal rather than tactile-proprioceptive integration.

Proprioceptive error of estimated fingertip position in two-dimensional space is reduced with the addition of tactile stimulation applied at the fingertip. Tactile input does not disrupt the participants' estimation strategy, as the individual error vector maps maintain their overall structure. This relationship suggests integration of proprioception and tactile information improves proprioceptive estimation, which can also be improved with trained mental focus and attention. Task attention and arousal are physiologically regulated by the reticular activating system (RAS), a brainstem circuit including the locus coeruleus (LC). There is direct and indirect evidence that these structures can be modulated by non-invasive trigeminal nerve stimulation (nTNS), providing an opportunity to examine nTNS effect on the integrative relationship of proprioceptive and tactile information. Fifteen right-handed participants performed a simple right-handed proprioceptive estimation task with tactile feedback (touch) and no tactile (hover) feedback. Participants repeated the task after nTNS administration. Stimulation was delivered for 10 min, and stimulation parameters were 3,000 Hz, 50 μs pulse width, with a mean of 7 mA. Error maps across the workspace are generated using polynomial models of the participants' target responses. Error maps did not demonstrate significant vector direction changes between conditions for any participant, indicating that nTNS does not disrupt spatial proprioception estimation strategies. A linear mixed model regression with nTNS epoch, tactile condition, and the interaction as factors demonstrated that nTNS reduced proprioceptive error under the hover condition only. We argue that nTNS does not disrupt spatial proprioceptive error maps but can improve proprioceptive estimation in the absence of tactile feedback. However, we observe no evidence that nTNS enhances tactile-proprioceptive integration as the touch condition does not exhibit significantly reduced error after nTNS.

Dramatic Reanimation and Spontaneous Re-Canalization of a Fourth Ventricular Hemorrhage: “REVIVE” Phenomenon

Background Intraventricular hemorrhage is a calamitous type of stroke where bleeding into the ventricular system can be defined as: primary, if confined within the ventricles; or secondary, due to intracerebral hemorrhage extending from adjacent parenchyma. Intraventricular blood clot can lead to secondary insult and inflammatory responses that culminates in hydrocephalus as the most common cause of death. Purpose THerein, we report a patient with a high modified Graeb scale and low Glasgow coma scale. She spontaneously recanalized her fourth ventricle, decompressed her reticular activating system with remarkable spontaneous bilateral eye opening, and a consequently experienced a halfway drop in her mGS. Results This is the first reported case of a spontaneous recanalization of 4th ventricle obstruction secondary to IVH without intervention and subsequent dramatic neurological improvement. We believe that the apixaban primarily preserved the liquid state of hemorrhage and her presumed elevated ICP was sufficient to push out the liquified blood in the 4th ventricle into the upper spinal canal , recanalizing the 4th ventricle by continuously creating downward CSF pressure waves. Given the RAS location around the 4th ventricle, we hypothesize spontaneous decompression from the clot lysis triggered the RAS activation with sudden arousal manifested as spontaneous bilateral eyes opening. Hence, we refer to this as the reticular activating system reactivation after ventricular hemorrhage evacuation, or simply the “REVIVE” phenomenon. Conclusion This dramatic improvement from coma to awake state is worthy of recognition for future neurotherapeutic interventions.

Low arousal threshold is associated with altered functional connectivity of the ascending reticular activating system in patients with obstructive sleep apnea

A low arousal threshold (LAT) is a pathophysiological trait of obstructive sleep apnea (OSA) that may be associated with brainstem ascending reticular activating system-cortical functional connectivity changes. We evaluated resting-state connectivity between the brainstem nuclei and 105 cortical/subcortical regions in OSA patients with or without a LAT and healthy controls. Twenty-five patients with moderate to severe OSA with an apnea–hypopnea index between 20 and 40/hr (15 with and 10 without a LAT) and 15 age- and sex-matched controls were evaluated. Participants underwent functional magnetic resonance imaging after overnight polysomnography. Three brainstem nuclei—the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA)—associated with OSA in our previous study were used as seeds. Functional connectivity values of the two brainstem nuclei (LC and LDTg) significantly differed among the three groups. The connectivity of the LC with the precuneus was stronger in OSA patients than in controls regardless of the concomitant LAT. The connectivity between the LDTg and the posterior cingulate cortex was also stronger in OSA patients regardless of the LAT. Moreover, OSA patients without a LAT showed stronger LDTg-posterior cingulate cortex connectivity than those with a LAT (post hoc p = 0.013), and this connectivity strength was negatively correlated with the minimum oxygen saturation in OSA patients (r = − 0.463, p = 0.023). The LAT in OSA patients was associated with altered LDTg-posterior cingulate cortex connectivity. This result may suggested that cholinergic activity may play a role in the LAT in OSA patients.

Waxing and waning consciousness in a patient with a midbrain cavernous malformation: illustrative case.

Understanding the intricate relationship between consciousness and the midbrain's structures remains a significant challenge in neuroscience. Transient lesions are perfect examples of the physiological functioning mechanism of these structures. The authors present the case of a 49-year-old female who experienced a transient disorder of consciousness due to a midbrain hematoma following surgical interventions to remove a cavernous malformation in the midbrain. This case explores the interplay between the ascending reticular activating system (ARAS) and the thalamic centers, highlighting the role of structural disruptions in influencing consciousness levels. Notably, the patient's recovery correlated with the resolution of midbrain edema, reinstating normal ARAS function and consciousness. In patients affected by midbrain lesions, edema can lead to a fluctuating neurological status, which can be difficult to diagnose. This case highlights the midbrain's crucial role in the consciousness network and the need to comprehend the intricate connections between subcortical and cortical structures for a comprehensive understanding of human consciousness. https://thejns.org/doi/10.3171/CASE2411.

From emotional arousal to executive action. Role of the prefrontal cortex.

Emotional arousal is caused by the activity of two parallel ascending systems targeting mostly the subcortical limbic regions and the prefrontal cortex. The aversive, negative arousal system is initiated by the activity of the mesolimbic cholinergic system and the hedonic, appetitive, arousal is initiated by the activity of the mesolimbic dopaminergic system. Both ascending projections have a diffused nature and arise from the rostral, tegmental part of the brain reticular activating system. The mesolimbic cholinergic system originates in the laterodorsal tegmental nucleus and the mesolimbic dopaminergic system in the ventral tegmental area. Cholinergic and dopaminergic arousal systems have converging input to the medial prefrontal cortex. The arousal system can modulate cortical EEG with alpha rhythms, which enhance synaptic strength as shown by an increase in long-term potentiation (LTP), whereas delta frequencies are associated with decreased arousal and a decrease in synaptic strength as shown by an increase in long-term depotentiation (LTD). It is postulated that the medial prefrontal cortex is an adaptable node with decision making capability and may control the switch between positive and negative affect and is responsible for modifying or changing emotional state and its expression.

Mechanisms of Laser Acupuncture – Hypotheses and Evidence

Laser acupuncture, a rising complementary therapy, applies a low-intensity laser to acupuncture points, yet its underlying mechanisms remain unclear. Proposed hypotheses include modulation of cellular signaling, tissue repair, and immune modulation. Laser acupuncture may stimulate energy flow, neurotransmitter release, cellular changes, immune regulation, and neuroendocrine activity. Additionally, the biophoton theory suggests an involvement of ultra-weak photon radiation from cells. Litscher et al. explore these mechanisms through neurophysiological analysis, biochemical measurements, imaging techniques, and clinical trials. They documented subtle human brain responses following laser stimulation, potentially modulating the ascending reticular activating system. However, further research is needed to validate and expand these findings for broader clinical application of laser acupuncture.

Peduncular Hallucinosis: Clinical characteristics, etiology, and a case report

IntroductionVisual hallucinations are a relatively common neurological complaint. Peduncular hallucinosis (PH) stands out as a distinct entity, characterized by complex visual hallucinations resulting from structural lesions in the brainstem or diencephalon.ObjectivesWe aim to provide an overview of the clinical features, etiological factors, and management strategies associated with PH, incorporating a unique case study.MethodsClinical case report and brief literature review.ResultsClinical Characteristics: PH is marked by detailed, colorful, vivid, and occasionally emotionally charged visual hallucinations. These hallucinations encompass people, animals, or objects and may be mistaken for reality. While primarily visual, they may occasionally involve other sensory modalities. Crucially, patients with PH maintain insight, distinguishing it from primary psychotic disorders.Etiological Factors: PH is most commonly associated with structural brainstem lesions, particularly in the midbrain. Potential instigators encompass ischemic strokes, vascular anomalies, tumors and infections. Disruption of the reticular activating system in the brainstem is implicated in the pathogenesis. Advanced imaging techniques have unveiled cases with subtle presentations, broadening our comprehension of PH.Pathogenesis: PH may involve the disturbance of serotonergic inhibitory pathways and the reticular activating system. A plausible link with hypnagogic hallucinations hints at a mechanism related to rapid REM sleep transitions.Case Report: Mr. J., a 30-year-old patient, suffered recurrent mesencephalic strokes attributed to Sneddon’s syndrome, ADA-2 deficiency, and protein C deficiency, leading to malacic lesions in the hemimesencephalon and right hemipons. He experienced complex visual hallucinations, primarily geometric patterns and animals, mainly at night. Importantly, he maintained insight into their hallucinatory nature. Mr. J. also had diplopia, visual impairment, recurrent headaches, and left hemiparesis.Reactive anxiety and depression due to functional loss followed his recurrent strokes. Initially, antipsychotics were used to manage sensory-perceptual disturbances, but were later discontinued due to reduced interference with daily functioning. Antidepressant and psychological therapy was continued throughout the follow-up to address mood symptoms.Conclusions Peduncular hallucinosis is an intriguing phenomenon characterized by complex visual hallucinations. Understanding its clinical features, etiology, and possible mechanisms is essential for accurate diagnosis and management. This case report emphasizes PH’s clinical aspects and the importance of a multidisciplinary approach, including pharmacological intervention and psychological support. Understanding its features, causes, and management is essential for accurate care. Further research is needed to improve our comprehension and optimize treatment strategies.Disclosure of InterestNone Declared

Effects of Neurofibromatosis Type 1 on Pseudoarthrosis and the Forensic Implications

Pseudoarthrosis is the presentation of false joints or non-union, primarily in long bones. While pseudoarthrosis most often presents as the lack of union between parts of a fractured or broken bone, it is also suspected that pseudoarthrosis results from a congenital disorder of unknown origin. While the etiology is unclear, there is an association with a congenital defect in neurofibromatosis type 1 gene through the neurofibromin protein. This defect occurs during the germ line mutation of conception and is often identified during early childhood. Pseudoarthrosis is more often difficult to detect in adults as it is frequently corrected during childhood. Germ line defects along the neurofibromin protein often result in a lack of communication from the reticular activating system (RAS) molecular signaling, which, in turn, impacts skeletal osteon production. Consequently, osseous lesions may develop and lead to a lack of cellular control over osteoblast signaling in the long bones of the skeleton. Understanding the origins of congenital pseudoarthrosis and its relationship with neurofibromatosis type 1 could lead to a better understanding of both conditions. Understanding these conditions can be useful for interpreting forensic contexts. These contexts include having the histological knowledge of osteology in these diseases for identification purposes. Given that both neurofibromatosis type 1 and pseudoarthrosis are uncommon conditions, their presence may aid forensic practitioners in determining cause of death or identification of the individual. This paper reviews new advances towards understanding the root cause of pseudoarthrosis.

From active affordance to active inference: vertical integration of cognition in the cerebral cortex through dual subcortical control systems.

In previous papers, we proposed that the dorsal attention system's top-down control is regulated by the dorsal division of the limbic system, providing a feedforward or impulsive form of control generating expectancies during active inference. In contrast, we proposed that the ventral attention system is regulated by the ventral limbic division, regulating feedback constraints and error-correction for active inference within the neocortical hierarchy. Here, we propose that these forms of cognitive control reflect vertical integration of subcortical arousal control systems that evolved for specific forms of behavior control. The feedforward impetus to action is regulated by phasic arousal, mediated by lemnothalamic projections from the reticular activating system of the lower brainstem, and then elaborated by the hippocampus and dorsal limbic division. In contrast, feedback constraint-based on environmental requirements-is regulated by the tonic activation furnished by collothalamic projections from the midbrain arousal control centers, and then sustained and elaborated by the amygdala, basal ganglia, and ventral limbic division. In an evolutionary-developmental analysis, understanding these differing forms of active affordance-for arousal and motor control within the subcortical vertebrate neuraxis-may help explain the evolution of active inference regulating the cognition of expectancy and error-correction within the mammalian 6-layered neocortex.

Pilot Study of Reticular Activating System (RAS) in Mild Dementia

AbstractBackgroundClinically, the common early symptoms of dementia include memory problems, reduced concentration, behaviour changes, apathy and withdrawal, loss of ability to do everyday tasks. These cognitive functions are mediated by the reticular activating system (RAS) that is a collection of interconnected brain nuclei that regulates wakefulness, alertness and modulate behaviors. The RAS degenerates early during Alzheimer’s disease progression in association with abnormal tau build‐up.MethodThis study aimed to explore the relationship between the RAS functioning and older people with mild grade dementia. The Kendrick Object Learning Test (KOLT) is a test of recall of everyday objects after viewing for a brief period, an immediate recall of briefly perceived visual data. The Kendrick Digit Copying Test (KDCT) is a test of speed in processing and recording information. These tests suggested cortical excitation mediated by both the RAS and the hypothalamic limbic network which deteriorate in older people with mild grade dementia.ResultIn this pilot study, 25 demented patients with mild grade dementia and 20 participants with known depression were recruited. They are matched in age (mean age 72 with sd 4.89) and shared similar demographic background. The participants were tested with the Kendrick Object Learning Test (KOLT) and the Kendrick Digit Copying Test (KDCT). To observe the short term longitudinal change of their RAS functioning, these tests were administered again 4 weeks following baseline. With regular day activity treatment, the depressive group showed improvement in KOLT (p < 0.1), but not on KDCT (p = .82). However, in the dementia group, there were no significant difference noted in both KOLT and KDCT (p < 0.5).ConclusionThe present findings echo some findings of RAS does not function properly as in the older people with dementia. The reticular system is not compromised in group of depressive participants, there would be improvement in object learning, but no significant difference on speed in processing and recording information as measured by speed‐performance tests (KDCT). Proper and targeted rehabilitation trainings and care giving techniques could be arranged in meeting the specific patients’ needs.

Contribution of sleep quality changes on ascending reticular activating system structural and functional integrity in ageing – a multimodal MRI study

Contribution of sleep quality changes on ascending reticular activating system structural and functional integrity in ageing – a multimodal MRI study

Combined effects of transcranial direct current stimulation and aerobic exercise on inhibitory control function in healthy young adults: An event-related potential study

Transcranial direct current stimulation (tDCS) and aerobic exercise (AE) have been demonstrated to enhance inhibitory control function in healthy individuals separately. However, the potential benefits of combining these two interventions have yet to be fully explored. In this study, we aimed to use multiple event-related potential (ERP) components (P200, N200, and N450) to investigate the combined effects of tDCS and AE on the improvement of inhibitory control ability in healthy young adults. We evaluated the influence of this combined intervention on cognitive tasks involving inhibitory control function and basic information processing by performing the Stroop Word Color task. Our results showed that compared to the application of tDCS or AE alone, the combined intervention of tDCS and AE had a greater effect on improving inhibitory control function in healthy young adults. The amplitude of P200, N200, and N450 ERP components also changed more significantly during the Stroop Word Color task. We concluded that the mechanism of tDCS combined with AE in improving inhibitory control ability may involve synergistic effects on brain structures at different levels, such as regulating interactions at the reticular activating system level and activating corresponding brain regions at the medial frontal lobe and frontal lobe levels.

Investigating the effects of a FAAH inhibitor in the laterodorsal tegmental nucleus using a new ex vivo mouse preparation

As part of the brainstem reticular activating system, the laterodorsal tegmentum (LDT) is a central player in regulating sleep, arousal, and motivated behaviors including addiction. The neuronal lipids within the LDT that could regulate neuronal activity and LDT signaling are not fully characterized due, in part, to the complication of the presence of fatty acid amide hydrolases (FAAH). To determine the lipids in the LDT, mouse brain slices at different stages of brain development (16, 26 and 66 days) were exposed ex vivo to the FAAH inhibitor oleyl trifluoromethyl ketone (OTMK). Metabolomics and proteomic analyses were conducted on matched samples. Metabolomics analysis revealed differences between OTMK treated and untreated LDT. Furthermore, a distinct phenotype (proteomic profile) as a function of OTMK treatment was observed in LDT from adolescent (66 days) mice indicating an effect of treatment with OTMK at later stages of brain development. Our data indicate that this ex vivo preparation could facilitate screening of different FAAH inhibitors in mammalian tissues, and more importantly, this preparation should allow a deeper characterization of global mass spectrometry-based omics profiles within the LDT.

Modeling the role of the thalamus in resting-state functional connectivity: Nature or structure.

The thalamus is a central brain structure that serves as a relay station for sensory inputs from the periphery to the cortex and regulates cortical arousal. Traditionally, it has been regarded as a passive relay that transmits information between brain regions. However, recent studies have suggested that the thalamus may also play a role in shaping functional connectivity (FC) in a task-based context. Based on this idea, we hypothesized that due to its centrality in the network and its involvement in cortical activation, the thalamus may also contribute to resting-state FC, a key neurological biomarker widely used to characterize brain function in health and disease. To investigate this hypothesis, we constructed ten in-silico brain network models based on neuroimaging data (MEG, MRI, and dwMRI), and simulated them including and excluding the thalamus, and raising the noise into thalamus to represent the afferences related to the reticular activating system (RAS) and the relay of peripheral sensory inputs. We simulated brain activity and compared the resulting FC to their empirical MEG counterparts to evaluate model's performance. Results showed that a parceled version of the thalamus with higher noise, able to drive damped cortical oscillators, enhanced the match to empirical FC. However, with an already active self-oscillatory cortex, no impact on the dynamics was observed when introducing the thalamus. We also demonstrated that the enhanced performance was not related to the structural connectivity of the thalamus, but to its higher noisy inputs. Additionally, we highlighted the relevance of a balanced signal-to-noise ratio in thalamus to allow it to propagate its own dynamics. In conclusion, our study sheds light on the role of the thalamus in shaping brain dynamics and FC in resting-state and allowed us to discuss the general role of criticality in the brain at the mesoscale level.

Neuroimaging in Coma, Brain Death, and Related Conditions

Coma is a state of unresponsiveness to external stimuli, which can be secondary to a variety of CNS alterations affecting essential neuronal pathways, particularly the ascending reticular activating system. A comprehensive clinical evaluation is necessary for assessment of motor function and brainstem reflexes but is often insufficient for determination of the underlying etiology and extent of injury. Diagnostic brain imaging is typically needed for management and decision-making, particularly in acute settings where prompt diagnosis of reversible/treatable conditions is essential, as well as for prognostication. Understanding the pathophysiologic mechanisms leading to coma and comalike states and their imaging manifestations will enable selection of appropriate modalities and facilitate a clinically relevant interpretation. For evaluation of brain death, diagnostic imaging has a supportive role, and when indicated, selection of an ancillary diagnostic test is based on multiple factors, including susceptibility to confounding factors and specificity, in addition to safety, convenience, and availability.Learning objective: To describe the pathophysiology of alterations of consciousness and discuss the role of neuroimaging modalities in the evaluation of coma, brain death, and associated conditions

The effect of brain exercise for improving cognitive function among cognitively impaired batik workers: A preliminary study in Indonesia

AbstractBackgroundBrain exercise, also known as Brain Gym, aims to maintain brain health by exercising. The movements in brain exercise are focused to train contralateral and ipsilateral coordination, namely by doing hand and foot movements on different sides and the same side alternately. Brain exercise can restore the reticular activating system in the brain so that it can improve memory abilities. This study aimed to identify the effect of brain exercise for improving cognitive function among batik workers who had cognitiveMethodThis study was one group pretest and posttest design. We conducted brain exercise on 47 batik workers with cognitive impairment who were chronically exposed to heavy metals in 2 batik centers in Gulurejo Village, Lendah, Kulonprogo, Indonesia. Subjects were examined for cognitive function before treatment using MoCA‐INA (Montreal Cognitive Assessment‐Indonesia version). The treatment of brain exercise was done 2 times a week for 3 months, with duration of exercise was 10 minutes. The cognitive function of the research subjects was re‐examined after 1 and 3 months of brain exercise.ResultThe mean age of the subject was 44 years‐old, with the median duration of being batik worker was 4 years (1‐15 years). The mean MoCA‐Ina score before treatment was 19.21 ± 4.86. After 1 month of treatment, there was an increase of MoCA‐INA score to 19.91 ± 4.81. After 3 months of treatment, the MoCA‐INA score futher increased to 22.45 ± 4.74. When further analyzed for each domain, we found that there were no differences after 1 month. However, there was a significant increase in the domains of attention (p = 0.004), language (p = 0.002), abstraction (p = 0.10), delayed recall (p < 0.001) and orientation (p = 0.001) after 3 months exercise.ConclusionBrain exercise may benefit for improving cognitive function among batik workers with cognitive impairment. This study could potentially be applied for other population with dementia to help improving the clinical outcome.

Cook’s FSD Dysregulation: Functional System Regulation Using A Spiritual Growth-Oriented Learning Model 2.3

In accordance to the pathophysiology of dyslexia, the RAS (Reticular Activating System) and ACC (Anterior Cingulate Cortex) are two brain regions that are involved in noradrenergic signaling, which is the transmission of nerve impulses that involve the neurotransmitter noradrenaline

Altered functional connectivity of the ascending reticular activating system in obstructive sleep apnea

Repeated arousals during sleep in obstructive sleep apnea (OSA) may lead to altered functional connectivity (FC) of the ascending reticular activating system (ARAS). We evaluated resting-state FC between eight ARAS nuclei and 105 cortical/subcortical regions in OSA patients and healthy controls. Fifty patients with moderate to severe OSA and 20 controls underwent overnight polysomnography and resting-state functional magnetic resonance imaging. Seed-to-voxel analysis of ARAS–cortex FC was compared between OSA patients and controls. The ARAS nuclei included the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA). FC values of three ARAS nuclei (the LC, LDTg, and VTA) significantly differed between the groups. FC of the LC with the precuneus, posterior cingulate gyrus, and right lateral occipital cortex (LOC) was stronger in OSA patients than controls. FC between the LDTg and right LOC was stronger in OSA patients than controls, but FC between the VTA and right LOC was weaker. Average LC–cortex FC values positively correlated with the arousal, apnea, and apnea–hypopnea index in OSA patients. Alterations in ARAS–cortex FC were observed in OSA patients. The strength of LC–cortex noradrenergic FC was related to arousal or OSA severity in patients.

0510 Altered functional connectivity of the ascending reticular activating system in obstructive sleep apnea

Abstract Introduction Recurrent arousals in obstructive sleep apnea (OSA) may lead to alteration in functional connection involving in the ascending reticular activating system (ARAS). We aimed to evaluate resting-state functional connectivity (FC) between eight ARAS nuclei and 105 cortical/subcortical regions in OSA patients and matched controls. Methods Total of 50 patients with moderate to severe OSA and 20 controls without OSA underwent overnight polysomnography (PSG) and resting-state functional magnetic resonance imaging in the following morning. Seed to voxel analysis of ARAS-cortical FC was compared between the patients and controls. The ARAS nuclei included dorsal and median raphe nucleus, locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), pedunculopontine tegmental nucleus, pontine nucleus oralis, parabrachial complex, and ventral tegmental area (VTA). Correlations between average FC values of significant clusters and PSG parameters were calculated in the patients. Results FC values in the three of the ARAS nuclei (LC, LDTg, and VTA) were significantly different between the group. The FC value between the LC and the precuneus cortex, posterior cingulate gyrus, and right lateral occipital cortex (LOC) was increased in OSA patients compared to the controls. The FC value between the LDTg and right LOC was enhanced, but the FC one between the VTA and right LOC was reduced in the patients. The average LC-cortical FC values positively correlated with the arousal index(r=0.282, p=0.047), apnea index(r=0.325, p=0.021), or apnea-hypopnea index (r=0.302, p=0.033) in OSA patients. Conclusion The results of this study support alteration in ARAS-cortical FC in OSA patients. Degree of the noradrenergic LC-cortical FC may be related to arousal or OSA severity in the patients. Support (if any)

Problems in the Development of the Sleep-Wake Rhythm Influence Neurodevelopmental Disorders in Children.

Development of the sleep-wake rhythm has a significant effect on the physical and mental development of children. The sleep-wake rhythm is controlled by aminergic neurons in the brainstem's ascending reticular activating system, which is associated with synaptogenesis and the promotion of brain development. The sleep-wake rhythm develops rapidly within the first year after birth. At 3-4 months of age, the framework of the circadian rhythm is established. The objective of the present review is to assess a hypothesis concerning problems in the development of the sleep-wake rhythm and their effect on neurodevelopmental disorders. Autism spectrum disorder is characterised by a delay in the development of sleep rhythms at 3-4 months of age and also insomnia and night-time awakenings, as supported by several reports. Melatonin may shorten the sleep latency in ASD. Rett syndrome sufferers kept awake during the daytime were analysed by the Sleep-wake Rhythm Investigation Support System (SWRISS) (IAC, Inc., (Tokyo, Japan)), and the cause was found to be the dysfunction of aminergic neurons. Children and adolescents with attention deficit hyperactivity disorder show sleep problems such as resistance to bedtime, difficulty falling asleep, sleep apnoea, and restless legs syndrome. Sleep deprivation syndrome in schoolchildren is deeply influenced by Internet use, games, and smartphones, and this syndrome affects emotion, learning, concentration, and executive functioning. Sleep disorders in adults are strongly considered to affect not only the physiological/autonomic nervous system but also neurocognitive/psychiatric symptoms. Even adults cannot avoid serious problems, much less children, and the impact of sleep problems is considerably greater in adults. Paediatricians and nurses should be aware of the significance, from birth, of sleep development and sleep hygiene education for carers and parents. This research was reviewed and approved by the ethical committee of the Segawa Memorial Neurological Clinic for Children (No. SMNCC23-02).