Reticular Activating System Research Articles

Recovery of consciousness after a brainstem cavernous malformation hemorrhage: A descriptive study of preserved reticular activating system with tractography

The aim of this study is to describe the imaging features, the relevant anatomy, and the fractional anisotropy (FA) values in diffusion tensor tractography (DTT) of the ascending reticular activating system (ARAS) fiber tracts in 2 patients who recovered from initial altered consciousness after presenting with a brainstem cavernous malformation (BSCM) hemorrhage. A DTT was performed in 2 patients with impaired consciousness after a brainstem cavernous malformation hemorrhage. A 1.5 T scanner was used to obtain the axial tensors. Post-processing was performed and the mean FA values were recorded. The FA maps were used to seed the following regions of interest: the ventromedial midbrain, the anterior thalamus bilaterally, and the hypothalamus bilaterally. The first case presented with posterior displacement of the dorsal raphè fiber tracts, with preservation of all the ascending reticular activating fiber tracts and spontaneous recovery of consciousness after 20 days. The second case presented with no destruction but also had posterior displacement of the inferior dorsal raphè fiber tracts, with recovery of consciousness 1 month after resection surgery. Described in this study are affected fibers of the ARAS, as well as the FA value abnormalities in 2 patients, with recovery of a transient disorder of consciousness after a BSCM hemorrhage.

Class II histone deacetylases require P/Q-type Ca2+ channels and CaMKII to maintain gamma oscillations in the pedunculopontine nucleus

Epigenetic mechanisms (i.e., histone post-translational modification and DNA methylation) play a role in regulation of gene expression. The pedunculopontine nucleus (PPN), part of the reticular activating system, manifests intrinsic gamma oscillations generated by voltage-dependent, high threshold N- and P/Q-type Ca2+ channels. We studied whether PPN intrinsic gamma oscillations are affected by inhibition of histone deacetylation. We showed that, a) acute in vitro exposure to the histone deacetylation Class I and II inhibitor trichostatin A (TSA, 1 μM) eliminated oscillations in the gamma range, but not lower frequencies, b) pre-incubation with TSA (1 μM, 90–120 min) also decreased gamma oscillations, c) Ca2+ currents (ICa) were reduced by TSA, especially on cells with P/Q-type channels, d) a HDAC Class I inhibitor MS275 (500 nM), and a Class IIb inhibitor Tubastatin A (150–500 nM), failed to affect gamma oscillations, e) MC1568, a HDAC Class IIa inhibitor (1 μM), blocked gamma oscillations, and f) the effects of both TSA and MC1568 were blunted by blockade of CaMKII with KN-93 (1 μM). These results suggest a cell type specific effect on gamma oscillations when histone deacetylation is blocked, suggesting that gamma oscillations through P/Q-type channels modulated by CaMKII may be linked to processes related to gene transcription.

Deep brain stimulation for the treatment of disorders of consciousness and cognition in traumatic brain injury patients: a review.

Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.

A stochastic approach to serotonergic fibers in mental disorders

Virtually all brain circuits are physically embedded in a three-dimensional matrix of fibers that release 5-hydroxytryptamine (5-HT, serotonin). The density of this matrix varies across brain regions and cortical laminae, and it is altered in some mental disorders, including Major Depressive Disorder and Autism Spectrum Disorder. We investigate how the regional structure of the serotonergic matrix depends on the stochastic behavior of individual serotonergic fibers and introduce a new framework for the quantitative analysis of this behavior. In particular, we show that a step-wise random walk, based on the von Mises-Fisher probability distribution, can provide a realistic and mathematically concise description of these fibers. We also consider other stochastic models, including the fractional Brownian motion. The proposed approach seeks to advance the current understanding of the ascending reticular activating system (ARAS) and may also support future theory-guided therapeutic approaches.

Relationship between consciousness and injury of ascending reticular activating system in patients with hypoxic ischaemic brain injury

Impaired consciousness is one of the main sequelae of hypoxic ischemic brain injury(HI-BI).1 The ascending reticular activating system (ARAS) comprised arousal pathways and awareness networks, which mainly originates in the...

New benzodiazepines for sedation.

There are currently new drugs being developed that have benzodiazepine properties. This review will examine remimazolam, 3-hydroxyphenazapam, adinazolam, clonazolam, and deschloroetizolam as well as other novel agents. All benzodiazepines are protein bound and only moderately lipid soluble. In addition to their baseline properties, they can be enzymatically broken down into active metabolites. The mechanism of action of these medications is related to polysynaptic pathway inhibition via direct interaction with GABA and modifiable chloride channels. The main neurological areas of involvement are primarily the amygdala and reticular activating system. Benzodiazepines are used for sedation and for adjuvants to general anesthetics and not as primary induction agents. We describe the characteristics of newer drugs being developed, including their pharmacologic profile, side effects and efficacy, as well as the most recent clinical trials and future directions in benzodiazepine development.

Hypersomnia due to injury of the lower ventral ascending reticular activating system in a patient with intraventricular hemorrhage

Hypersomnia due to injury of the lower ventral ascending reticular activating system in a patient with intraventricular hemorrhage

Relating structural and functional brainstem connectivity to disease measures in epilepsy.

While epilepsy studies rarely examine brainstem, we sought to examine the hypothesis that temporal lobe epilepsy (TLE) leads to subcortical arousal center dysfunction, contributing to neocortical connectivity and neurocognitive disturbances. In this case-control study of 26 adult patients with TLE and 26 controls, we used MRI to measure structural and functional connectivity of the cuneiform/subcuneiform nuclei (CSC), pedunculopontine nucleus, and ventral tegmental area. Ascending reticular activating system connectivity patterns were related to neuropsychological and disease measures. Compared to controls, patients with TLE demonstrated reductions in ascending reticular activating system structural and functional connectivity, most prominently to neocortical regions (p < 0.05, unpaired t tests, corrected). While reduced CSC structural connectivity was related to impaired performance IQ and visuospatial memory, diminished CSC functional connectivity was associated with impaired verbal IQ and language abilities (p < 0.05, Spearman ρ, t tests). Finally, CSC structural connectivity decreases were quantitatively associated with consciousness-impairing seizure frequency (p < 0.05, Spearman ρ) and the presence of generalized seizures (p < 0.05, unpaired t test), suggesting a relationship to disease severity. Connectivity perturbations in brainstem arousal centers are present in TLE and may contribute to neurocognitive problems. These studies demonstrate the underappreciated role of brainstem networks in epilepsy and may lead to novel neuromodulation targets to treat or prevent deleterious brain network effects of seizures in TLE.

Excessive Daytime Sleepiness and Injury of the Ascending Reticular Activating System Following Whiplash Injury.

Objectives: This study investigated injuries of the ascending reticular activating system (ARAS) following whiplash injury, in patients with excessive daytime sleepiness (EDS).Methods: Twenty-three patients with whiplash injury and 26 healthy control subjects were recruited for this study. Epworth Sleepiness Scale (ESS) was used for evaluating sleepiness. According to the ESS score, the patients were classified into two groups: subgroup A – ESS score <10, and subgroup B – ESS score ≥10. Three components of the ARAS (lower dorsal, lower ventral, and upper) were evaluated for fractional anisotropy (FA) and tract volume (TV).Results: No significant differences were observed in the FA and TV values of the lower dorsal and upper ARAS between the patient and control groups (p > 0.05). Conversely, the values of FA and TV in the lower ventral ARAS of the patient group were significantly lower than those of the control group (p < 0.05). Comparing the values of subgroups A and B, the TV value of subgroup B was significantly lower than subgroup A (p < 0.05). However, no significant differences were observed in the values of the FA and TV in the lower dorsal and upper ARAS, and the FA value in the lower ventral ARAS (p > 0.05).Conclusions: We found significant injury of the lower ventral ARAS in EDS patients with whiplash injury. These results suggest that diffusion tensor tractography (DTT) could provide useful information for detecting injuries of the ARAS following whiplash injury, in patients with EDS.

Modulation of motor cortical excitability with auditory stimulation.

Loud sounds have been demonstrated to increase motor cortex excitability when transcranial magnetic stimulation (TMS) is synchronized with auditory evoked N100 potential measured from electroencephalography (EEG). The N100 potential is generated by an afferent response to sound onset and feature analysis, and upon novel sound it is also related to the arousal reaction. The arousal reaction is known to originate from the ascending reticular activating system of the brain stem and to modulate neuronal activity throughout the central nervous system. In this study we investigated the difference in motor evoked potentials (MEPs) when deviant and novelty stimuli were randomly interspersed in a train of standard tones. Twelve healthy subjects participated in this study. Three types of sound stimuli were used: 1) standard stimuli (800 Hz), 2) deviant stimuli (560 Hz), and 3) novelty stimuli (12 different sounds). In each stimulus sequence 600 stimuli were given. Of these, 90 were deviant stimuli randomly placed between the standard stimuli. Each of 12 novel sounds was presented once in pseudorandomized order. TMS was randomly mixed with the sound stimuli so that it was either synchronized with the individual N100 or trailed the sound onset by 200 ms. All sounds elicited an increase in motor cortex excitability. The type of sound had no significant effect. We also demonstrated that TMS timed at 200-ms intervals caused a significant increment of MEPs. This contradicted our hypothesis that MEP amplitudes to TMS synchronized with N100 would be greater than those to TMS at 200 ms after a sound and remains unexplained. NEW & NOTEWORTHY We demonstrated modulation of motor cortical excitability with parallel auditory stimulus by combining navigated transcranial magnetic stimulation (TMS) with auditory stimuli. TMS was synchronized with auditory evoked potentials considered to be generated by the unconscious attention call process in the auditory system.

Ekplanasi Ilmiah Metode Hipnotis terhadap Otak Manusia

Hypnotic is a method to explore humans’ conscious mind in order to experience suggestion alteration following particular purpose. Previously, in Indonesia, hypnotic was dominantly known as one on crimes technique to rob the victims easily in short time. Then, public perception shifted after hypnotic action performed in stages to entertaintaudience. Recently, hypnotic has been applied to benefit patient, students or individual with biological and psychological pains. Unfortunately, the existence of hypnotic as a logical explanation have not been available in a comprehensible text for public understanding, although excessive empirical studies existed in multidiscipline ways. This review article propose a scientific explanation toward hypnotic and its application such medical and educational purposes, based on a scientific philosophy. To conclude, hypnotic concept developed according to Deductive-Nomologies Explanation Scientific Model and fulfill positivistic and naturalistic truth paradigm and pragmatic truth theory. Its brief scientific explanation that is hypnotic processes with support of brain structure and mechanism. Scientific terms and concepts which are been involved are cerebrum, autonomous nervous system, reticular activating system, medulla oblongata, brainstem, corpus collosum, brain wave frequencies alteration, and chemically control of serotonine and endorphin.

Trigeminal, Visceral and Vestibular Inputs May Improve Cognitive Functions by Acting through the Locus Coeruleus and the Ascending Reticular Activating System: A New Hypothesis

It is known that sensory signals sustain the background discharge of the ascending reticular activating system (ARAS) which includes the noradrenergic locus coeruleus (LC) neurons and controls the level of attention and alertness. Moreover, LC neurons influence brain metabolic activity, gene expression and brain inflammatory processes. As a consequence of the sensory control of ARAS/LC, stimulation of a sensory channel may potential influence neuronal activity and trophic state all over the brain, supporting cognitive functions and exerting a neuroprotective action. On the other hand, an imbalance of the same input on the two sides may lead to an asymmetric hemispheric excitability, leading to an impairment in cognitive functions. Among the inputs that may drive LC neurons and ARAS, those arising from the trigeminal region, from visceral organs and, possibly, from the vestibular system seem to be particularly relevant in regulating their activity. The trigeminal, visceral and vestibular control of ARAS/LC activity may explain why these input signals: (1) affect sensorimotor and cognitive functions which are not directly related to their specific informational content; and (2) are effective in relieving the symptoms of some brain pathologies, thus prompting peripheral activation of these input systems as a complementary approach for the treatment of cognitive impairments and neurodegenerative disorders.

Role of calcium channels in bipolar disorder.

Bipolar disorder is characterized by a host of sleep-wake abnormalities that suggests that the reticular activating system (RAS) is involved in these symptoms. One of the signs of the disease is a decrease in high frequency gamma band activity, which accounts for a number of additional deficits. Bipolar disorder has also been found to overexpress neuronal calcium sensor protein 1 (NCS-1). Recent studies showed that elements in the RAS generate gamma band activity that is mediated by high threshold calcium (Ca2+) channels. This mini-review provides a description of recent findings on the role of Ca2+ and Ca2+ channels in bipolar disorder, emphasizing the involvement of arousal-related systems in the manifestation of many of the disease symptoms. This will hopefully bring attention to a much-needed area of research and provide novel avenues for therapeutic development.

Modafinil for treatment of coma and unresponsiveness associated with edema of the reticular activating system (RAS) in a pediatric patient

Modafinil for treatment of coma and unresponsiveness associated with edema of the reticular activating system (RAS) in a pediatric patient

EEG and Psychometry

It is an old adage in physiology that structure reflects function. In the brain-stem reticular activating system (RAS) there reside three nests of cells making peculiar chemicals known as the biogenic amines, viz. noradrenaline, dopamine and 5-hydroxytryptamine (5HT). What is more, the ramifications of these cells are distributed over the whole extent of the cerebral cortex. What is their function?

Restoration of an injured lower dorsal ascending reticular activating system in a patient with intraventricular hemorrhage.

Restoration of an injured lower dorsal ascending reticular activating system in a patient with intraventricular hemorrhage.

Why do we sleep?

According to a simple behavioral definition, sleep is a reversible behavioral state of perceptual disengagement from and unresponsiveness to the environment. Sleep is dividing into two states: Non-rapid eye movement (NREM) sleep which is subdivided into three stages (N1, N2, N3); and rapid eye movement (REM) sleep characterized by rapid eye movements, muscle atonia and desynchronized EEG. Mammalian sleep and wake states are regulated by multiple neuronal systems located in the brainstem, diencephalon, and telencephalon. Wakefulness is maintained by activation of the ascending reticular activating system involving several neurotransmitters including glutamate, acetylcholine and the monoamines. NREM sleep onset is associated with a reduction in activation of the ascending reticular activating system and an increase in neural activity within the ventrolateral preoptic area, anterior hypothalamus and basal forebrain. REM sleep is triggered by activation of cholinergic neurons in the laterodorsal and pedunculopontine tegmental nuclei. The suppression of motor activity in REM sleep is generated by glutamate-mediated activation of descending medullary reticular formation. The two-process model postulates that a homeostatic process rises during waking and declines during sleep and interacts with a circadian process that is not directly dependent of sleep and waking. Sleep function remains controversial. Sleep is thought to be restorative, conservative, adaptive, thermoregulatory and memory consolidative functions. Sleep also serves host-defense mechanisms and conserves caloric expenditures. Emerging evidences indicated that sleep replenishes brain energy stores and that sleep serves a glymphatic function by removing toxic byproducts of waking activity. Finally, there is experimental evidence that connectivity changes with sleep, sleep loss, and with changing afferent input, and that those changes are linked to sleep regulatory mechanisms. Sleep medicine as a medical specialty has existed for more than 30 years. The study on over 90 kinds of sleep disorders has shed light on the understanding to the mechanisms of sleep. For example, the finding of the role of hypocretin/orexin in the patho-physiology of narcolepsy led to the reveal of hypocretin/orexin as a major wakefulness promoting substance. The evolution of the field will help us recognize the impact of sleep disorders on society as well as the nature of sleep itself.

Effects of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPTG) of the reticular activating system (RAS) in Parkinson's disease (PD): motor and non motor benefits

Effects of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPTG) of the reticular activating system (RAS) in Parkinson's disease (PD): motor and non motor benefits

Voluntary modulation of mental effort investment: an fMRI study

Mental effort is a common phenomenological construct deeply linked to volition and self-control. While it is often assumed that the amount of exertion invested in a task can be voluntarily regulated, the neural bases of such faculty and its behavioural effects are yet insufficiently understood. In this study, we investigated how the instructions to execute a demanding cognitive task either “with maximum exertion” or “as relaxed as possible” affected performance and brain activity. The maximum exertion condition, compared to relaxed execution, was associated with speeded motor responses without an accuracy trade-off, and an amplification of both task-related activations in dorsal frontoparietal and cerebellar regions, and task-related deactivations in default mode network (DMN) areas. Furthermore, the visual cue to engage maximum effort triggered an anticipatory widespread increase of activity in attentional, sensory and executive regions, with its peak in the brain stem reticular activating system. Across individuals, this surge of activity in the brain stem, but also in medial wall cortical regions projecting to the adrenal medulla, positively correlated with increases in heart rate, suggesting that the intention to willfully modulate invested effort involves mechanisms related to catecholaminergic transmission and a suppression of DMN activity in favor of externally-directed attentional processes.

Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function

A method called Quantitative Ultra-Short Time-to-Echo Contrast Enhanced (QUTE-CE) Magnetic Resonance Imaging (MRI) which utilizes superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent to yield positive contrast angiograms with high clarity and definition is applied to the whole live rat brain. QUTE-CE MRI intensity data are particularly well suited for measuring quantitative cerebral blood volume (qCBV). A global map of qCBV in the awake resting-state with unprecedented detail was created via application of a 3D MRI rat brain atlas with 173 segmented and annotated brain areas. From this map we identified two distributed, integrated neural circuits showing the highest capillary densities in the brain. One is the neural circuitry involved with the primary senses of smell, hearing and vision and the other is the neural circuitry of memory. Under isoflurane anesthesia, these same circuits showed significant decreases in qCBV suggesting a role in consciousness. Neural circuits in the brainstem associated with the reticular activating system and the maintenance of respiration, body temperature and cardiovascular function showed an increase in qCBV with anesthesia. During awake CO2 challenge, 84 regions showed significant increases relative to an awake baseline state. This CO2 response provides a measure of cerebral vascular reactivity and regional perfusion reserve with the highest response measured in the somatosensory cortex. These results demonstrate the utility of QUTE-CE MRI for qCBV analysis and offer a new perspective on brain function and vascular organization.