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Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, and spastic paralysis due to involuntary muscle contraction in the hands and fingers can severely restrict skilled hand movements. However, the underlying neurological mechanisms remain unknown. Using a mouse model of spasticity after stroke, we demonstrate changes in neuronal activity with and without electrostimulation of the afferent nerve to induce the stretch reflex, measured using quantitative activation-induced manganese-enhanced magnetic resonance imaging. Neuronal activity increased within the ventral medullary reticular formation (MdV) in the contralesional brainstem during the acute post-stroke phase, and this increase was characterised by activation of circuits involved in spasticity. Interestingly, ascending electrostimulation inhibited the MdV activity on the stimulation side in normal conditions. Moreover, immunohistochemical staining showed that, in the acute phase, the density of GluA1, one of the α-amino-3 hydroxy‑5 methyl -4 isoxazolepropionic acid receptor (AMPAR) subunits, at the synapses of MdV neurons was significantly increased. In addition, the GluA1/GluA2 ratio in these receptors was altered at 2 weeks post-stroke, confirming homeostatic plasticity as the underlying mechanisms of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity at the acute post-stroke phase., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Abstract: We report on a patient with hypoxic-ischemic brain injury (HI-BI) who showed recovery from a minimally consciousness state over 6 years concurrent with recovery of an injured ascending reticular activating system (ARAS), which was demonstrated on diffusion tensor tractography (DTT).A 31-year-old female patient, who suffered from HI-BI, showed impaired consciousness with a minimally conscious state: intermittently obeying simple motor tasks, such as "please grasp my hand." Her consciousness showed recovery with the passage of time; rapid recovery was observed during the recent 2 years.In the upper ARAS, the neural connectivity to both the basal forebrain and prefrontal cortex had increased on 8-year DTT compared with 1.5-year DTT. In the lower dorsal and ventral ARAS, no significant change was observed between 1.5 and 8 years DTTs.Recovery of an injured ARAS was demonstrated in a patient who showed recovery from a minimally consciousness state over 6 years following HI-BI. Our results suggest the brain target areas for recovery of impaired awareness in patients with disorders of consciousness., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Humans with cervical spinal cord injury (SCI) often recover voluntary control of elbow flexors and, to a much lesser extent, elbow extensor muscles. The neural mechanisms underlying this asymmetrical recovery remain unknown. Anatomical and physiological evidence in animals and humans indicates that corticospinal and reticulospinal pathways differentially control elbow flexor and extensor motoneurons; therefore, it is possible that reorganization in these pathways contributes to the asymmetrical recovery of elbow muscles after SCI. To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the arm representation of the primary motor cortex, maximal voluntary contractions, the StartReact response (a shortening in reaction time evoked by a startling stimulus), and the effect of an acoustic startle cue on MEPs elicited by cervicomedullary stimulation (CMEPs) on biceps and triceps brachii in males and females with and without chronic cervical incomplete SCI. We found that SCI participants showed similar MEPs and maximal voluntary contractions in biceps but smaller responses in triceps compared with controls, suggesting reduced corticospinal inputs to elbow extensors. The StartReact and CMEP facilitation was larger in biceps but similar to controls in triceps, suggesting enhanced reticulospinal inputs to elbow flexors. These findings support the hypothesis that the recovery of biceps after cervical SCI results, at least in part, from increased reticulospinal inputs and that the lack of these extra inputs combined with the loss of corticospinal drive contribute to the pronounced weakness found in triceps. SIGNIFICANCE STATEMENT Although a number of individuals with cervical incomplete spinal cord injury show limited functional recovery of elbow extensors compared with elbow flexor muscles, to date, the neural mechanisms underlying this asymmetrical recovery remain unknown. Here, we provide for the first time evidence for increased reticulospinal inputs to biceps but not triceps brachii and loss of corticospinal drive to triceps brachii in humans with tetraplegia. We propose that this reorganization in descending control contributes to the asymmetrical recovery between elbow flexor and extensor muscles after cervical spinal cord injury., (Copyright © 2020 the authors.)

Traditionally, the brainstem has been seen as hardwired and poorly capable of plastic adaptations following spinal cord injury (SCI). Data acquired over the past decades, however, suggest differently: following SCI in various animal models (lamprey, chick, rodents, nonhuman primates), different forms of spontaneous anatomic plasticity of reticulospinal projections, many of them originating from the gigantocellular reticular nucleus (NRG), have been observed. In line with these anatomic observations, animals and humans with incomplete SCI often show various degrees of spontaneous motor recovery of hindlimb/leg function. Here, we investigated the functional relevance of two different modes of reticulospinal fiber growth after cervical hemisection, local rewiring of axotomized projections at the lesion site versus compensatory outgrowth of spared axons, using projection-specific, adeno-associated virus-mediated chemogenetic neuronal silencing. Detailed assessment of joint movements and limb kinetics during overground locomotion in female adult rats showed that locally rewired as well as compensatory NRG fibers were responsible for different aspects of recovered forelimb and hindlimb functions (i.e., stability, strength, coordination, speed, or timing). During walking and swimming, both locally rewired as well as compensatory NRG plasticity were crucial for recovered function, while the contribution of locally rewired NRG plasticity to wading performance was limited. Our data demonstrate comprehensively that locally rewired as well as compensatory plasticity of reticulospinal axons functionally contribute to the observed spontaneous improvement of stepping performance after incomplete SCI and are at least partially causative to the observed recovery of function, which can also be observed in human patients with spinal hemisection lesions. SIGNIFICANCE STATEMENT Following unilateral hemisection of the spinal cord, reticulospinal projections are destroyed on the injured side, resulting in impaired locomotion. Over time, a high degree of recovery can be observed in lesioned animals, like in human hemicord patients. In the rat, recovery is accompanied by pronounced spontaneous plasticity of axotomized and spared reticulospinal axons. We demonstrate the causative relevance of locally rewired as well as compensatory reticulospinal plasticity for the recovery of locomotor functions following spinal hemisection, using chemogenetic tools to selectively silence newly formed connections in behaviorally recovered animals. Moving from a correlative to a causative understanding of the role of neuroanatomical plasticity for functional recovery is fundamental for successful translation of treatment approaches from experimental studies to the clinics., (Copyright © 2020 the authors.)

Background and Purpose: Gait disturbance due to injuries of the descending motor pathway, including corticospinal tract (CST), corticoreticular pathway (CRP), and medial and lateral vestibulospinal tracts (VSTs), are commonly encountered disabling sequelae of pontine hemorrhage. We investigated relations between changes in the CST, CRP, and medial and lateral VST and corresponding changes in gait function in patients with pontine hemorrhage., Method: Nine consecutive stroke patients with pontine hemorrhage, and 6 age-matched normal subjects were recruited. Four patients were allocated to group A (can't walk independently) and 5 to group B (can walk independently). Diffusion tensor imaging (DTI) data were acquired twice at acute to subacute stage and chronic stage after stroke onset. Diffusion tensor tractography (DTT) was used to reconstruct CST, CRP, medial and lateral VST., Result: The CRP shows a significantly different between groups A and B in both initial and follow up DTT (p > 0.05). In contrast, CST, medial VST and lateral VST did not show a significant difference (p > 0.05). Regarding DTI parameters of CRPs in group A, percentages of patients with fractional anisotropy (FA) and mean diffusivity (MD) values more than two standard deviation from normal were higher by follow up DTI than by initial DTI, however, the CRPs in group B only showed increased abnormal range of MD., Conclusions: The CST does not play an essential role in recovery of independent walking and vestibulospinal tracts may not crucially affect recovery of independent walking in patients with pontine hemorrhage. In contrast, and intact CRP or changes of the CRP integrity appear to be related to the recovery of gait function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The pedunculopontine nucleus (PPN) included in the caudal mesencephalic reticular formation (cMRF) plays a key role in the control of locomotion and wake state. Regarding its involvement in the neurodegenerative process observed in Parkinson disease (PD), deep brain stimulation of the PPN was proposed to treat levodopa-resistant gait disorders. However, the precise role of the cMRF in the pathophysiology of PD, particularly in freezing of gait and other non-motor symptoms is still not clear. Here, using micro electrode recording (MER) in 2 primates, we show that dopamine depletion did not alter the mean firing rate of the overall cMRF neurons, particularly the putative non-cholinergic ones, but only a decreased activity of the regular neurons sub-group (though to be the cholinergic PPN neurons). Interestingly, a significant increase in the relative proportion of cMRF neurons with a burst pattern discharge was observed after MPTP intoxication. The present results question the hypothesis of an over-inhibition of the CMRF by the basal ganglia output structures in PD. The decreased activity observed in the regular neurons could explain some non-motor symptoms in PD regarding the strong involvement of the cholinergic neurons on the modulation of the thalamo-cortical system. The increased burst activity under dopamine depletion confirms that this specific spike discharge pattern activity also observed in other basal ganglia nuclei and in different pathologies could play a mojor role in the pathophysiology of the disease and could explain several symptoms of PD including the freezing of gait. The present data will have to be replicated in a larger number of animals and will have to investigate more in details how the modification of the spike discharge of the cMRF neurons in the parkinsonian state could alter functions such as locomotion and attentional state. This will ultimely allow a better comprehension of the pathophysiology of freezing of gait., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Recent evidence from both monkey and human studies suggests that the reticulospinal tract may contribute to recovery of arm and hand function after stroke. In this study, we evaluated a marker of reticulospinal output in stroke survivors with varying degrees of motor recovery., Methods: We recruited 95 consecutive stroke patients presenting 6 months to 12 years after their index stroke, and 19 heathy control subjects. Subjects were asked to respond to a light flash with a rapid wrist flexion; at random, the flash was paired with either a quiet or loud (startling) sound. The mean difference in electromyogram response time after flash with quiet sound compared with flash with loud sound measured the StartReact effect. Upper limb function was assessed by the Action Research Arm Test (ARAT), spasticity was graded using the Modified Ashworth Scale (MAS) and active wrist angular movement using an electrogoniometer., Results: StartReact was significantly larger in stroke patients than healthy participants (78.4 vs 45.0 ms, P < .005). StartReact showed a significant negative correlation with the ARAT score and degree of active wrist movement. The StartReact effect was significantly larger in patients with higher spasticity scores., Conclusion: We speculate that in some patients with severe damage to their corticospinal tract, recovery led to strengthening of reticulospinal connections and an enhanced StartReact effect, but this did not occur for patients with milder impairment who could use surviving corticospinal connections to mediate recovery.

We formulate a conductance-based model for a 3-neuron motif associated with Childhood Absence Epilepsy (CAE). The motif consists of neurons from the thalamic relay (TC) and reticular nuclei (RT) and the cortex (CT). We focus on a genetic defect common to the mouse homolog of CAE which is associated with loss of GABA A receptors on the TC neuron, and the fact that myelination of axons as children age can increase the conduction velocity between neurons. We show the combination of low GABA A mediated inhibition of TC neurons and the long corticothalamic loop delay gives rise to a variety of complex dynamics in the motif, including bistability. This bistability disappears as the corticothalamic conduction delay shortens even though GABA A activity remains impaired. Thus the combination of deficient GABA A activity and changing axonal myelination in the corticothalamic loop may be sufficient to account for the clinical course of CAE.

Rationale: We report on a stroke patient who showed restoration of discontinued corticoreticular pathways (CRPs) on serial diffusion tensor tractography (DTT) concurrent with recovery of gait disturbance following shunt operation for hydrocephalus., Patient Concerns: A 67-year-old female patient underwent stereotactic drainage for management of intraventricular hemorrhage due to a rupture of the left posterior communicating artery., Diagnoses: After 4 weeks from onset, the patient exhibited quadriparesis with more severe weakness in the proximal muscles and could not even stand or walk. She underwent comprehensive rehabilitation for 3 weeks. Her quadriparesis, as a result of hydrocephalus, did not improve significantly., Interventions: On the pre-op DTT, discontinuations (the right CRP: at subcortical white matter level, and the left CRP: at the midbrain level) of the CRP fibers from the premotor cortex were observed in both hemispheres., Outcomes: She underwent a ventriculo-peritoneal shunt operation and her quadriparesis improved, especially the proximal muscles. Consequently, she could walk with mild assistance on an even floor at 5 days and walk on stairs at 4 weeks after the shunt operation. On the post-op DTT, the discontinued CRP fibers were elongated to the premotor cortex in both hemispheres., Lessons: Restoration of discontinued CRPs concurrent with recovery of gait disturbance following shunt operation for hydrocephalus was demonstrated in a stroke patient.

Myoclonus is often a diagnostic and therapeutic challenge due to its broad phenomenological variability and limited therapeutic options. This article gives a short survey and characterizes in detail two common types of myoclonus, cortical myoclonus and reticular reflex myoclonus. Clinical testing and electrophysiological investigations provide relevant local diagnostic indications for the generating structure(s). Such indications would influence not only the strategies of neuroimaging and laboratory investigations aimed at clarifying the underlying cause but also the selection of drugs to suppress myoclonus.

The correlations between the indicators of cerebral hemodynamics and electrical activity in children with impaired motor skills of central origin (children with cerebral palsy) were investigated. There is established a high number of links between indicators of rheoencephalogram (REG) and electroencephalogram (EEG) in the left cerebral hemisphere than in the right. In frontomastoidal allocation 19 correlations and in occipitomastoidal - 59 links. We suppose that poor circulation in vertebroplasty-basilar system leads to the defeat of the brain stem, which, with afferent pathways of the reticular formation, connects the thalamus with the cortex. In the reticular formation there is an inhibition of ascending activators influences, which eland to decreasing of the cortex is tonus. You can talk about the functional immaturity of the system of nonspecific activation by the reticular formation of the brain stem. Children with violation of motor activity had significantly more negative and positive significant and high correlation among the existing indicators of electric brain activity and cerebral hemodynamics, in our opinion, is due to the development of interconnection compensation that is carried out by adjustment of the functional systems and the formation of new forms of adaptive responses in conditions of disontogenetik. Feature correlation pattern of the EEG, of children with disorders of motor activity, is associated with a significantly great number of high and significant correlations between measures of electrical brain activity in the δ- and q- rhythms, especially in the temporal areas of the cerebral cortex. According to visual analysis of EEG there is revealed a common manifestation of changes of bioelectric brain activity in children with disorders of motor activity. This is manifested in the development of paroxysmal activity of action potentials of θ- and δ-rhythms with the focus of activity in the anterior areas of the cerebral cortex; the formation of a mosaic representation of the θ-rhythms in temporal areas; the presence of hypersynchronous a-paroxysms in the posterior areas of the cerebral cortex. The given facts testify to activation of mechanisms of limbic-neocortical systems and synchronizing influences of the reticular formation of the stem and diencephalic structures. There is also detected greater number of correlations when occipitomastoidal registration was lone it reflects compensatory redistribution of cerebral blood flow over the affected structures of brain stem structures that are associated with the provision of cortical functions.

The purposes of this pilot study were to create a model of focal cortical ischemia in Macaca fascicularis and to explore contributions of the reticulospinal system in recovery of reaching. Endothelin-1 was used to create a focal lesion in the shoulder/elbow representation of left primary motor cortex (M1) of two adult female macaques. Repetitive microstimulation was used to map upper limb motor outputs from right and left cortical motor areas and from the pontomedullary reticular formation (PMRF). In subject 1 with a small lesion and spontaneous recovery, reaching was mildly impaired. Changes were evident in the shoulder/elbow representations of both the lesioned and contralesional M1, and there appeared to be fewer than expected upper limb responses from the left (ipsilesional) PMRF. In subject 2 with a substantial lesion, reaching was severely impaired immediately after the lesion. After 12 weeks of intensive rehabilitative training, reach performance recovered to near-baseline levels, but movement times remained about 50% slower. Surprisingly, the shoulder/elbow representation in the lesioned M1 remained completely absent after recovery, and there was a little change in the contralesional M1. There was a definite difference in motor output patterns for left versus right PMRF for this subject, with an increase in right arm responses from right PMRF and a paucity of left arm responses from left PMRF. The results are consistent with increased reliance on PMRF motor outputs for recovery of voluntary upper limb motor control after significant cortical ischemic injury.

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus-hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed.

It is now well established that the cerebellum receives input from nociceptors which may serve to adjust motor programmes in response to pain and injury. In this study, we investigated the possibility that spinoreticular neurons (SRT) which project to a pre-cerebellar nucleus, the lateral reticular nucleus (LRt), respond to noxious mechanical stimulation. Seven adult male rats received stereotaxic injections of the b subunit of cholera toxin in the LRt. Following a 5 day interval, animals were anesthetised with urethane and a noxious mechanical stimulus was applied to the right hind paw. Animals were fixed by perfusion 5min following application of the stimulus. Retrogradely labelled SRT neurons of the lumbar spinal cord were examined for immunoreactivity for phosphorylated ERK (pERK) and the neurokinin-1 (NK-1) receptor. Approximately 15% of SRT cells in deep laminae (IV-VII and X) expressed pERK ipsilateral to the site of the stimulus. Around 60% of SRT cells with the NK-1 receptor expressed pERK but 5% of pERK expressing cells were negatively labelled for NK-1. It is concluded that a significant proportion of SRT cells projecting to the LRt respond to noxious mechanical stimuli and that one of the functions of this pathway may be to provide the cerebellum with nociceptive information., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Sudden infant death syndrome (SIDS) is a major cause of infant mortality throughout the world, yet its cause and mechanism of action remain poorly understood. Here, we discuss a novel model of the etiology of SIDS which ties together what is known about the brain regions thought to be affected in SIDS infants with a defined neuroanatomical circuit and a documented preventative factor in young children. We propose that SIDS occurs due to a lack of sufficient development and plasticity of glutamatergic synapses in the mesencephalic nucleus of the trigeminal nerve (Me5) and reticular formation (RF) of the brainstem. This model is supported by evidence of brainstem dysfunction in SIDS as well as evidence of signaling through the Me5 and RF in another means of regulating cortical arousal. Furthermore, long-term plasticity of glutamatergic synapses is well known to play a critical role in learning and memory in other regions of the brain, implying that those mechanisms may also be relevant in the development of brainstem circuitry. This model clearly explains why SIDS deaths appear so suddenly with little pathological explanation and suggests a potentially novel way to prevent these deaths from occurring., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study investigated the intrinsic connections of a key-structure of the endogenous pain inhibitory system, the pedunculopontine tegmental nucleus (PPTN), in post-ictal antinociceptive process through synaptic inactivation of the PPTN with cobalt chloride. Male Wistar rats (n = 6 or 7 per group), weighing 250-280 g, had the tail-flick baseline recorded and were submitted to a stereotaxic surgery for the introduction of a guide-cannula aiming at the PPTN. After 5 days of postoperative recovery, cobalt chloride (1 mM/0.2 µL) or physiological saline (0.2 µL) were microinjected into the PPTN and after 5 min, the tail-withdrawal latency was measured again at 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 min after seizures evoked by intraperitoneal injection of pentylenetetrazole (64 mg/kg). The synaptic inactivation of PPTN decreased the post-ictal antinociceptive phenomenon, suggesting the involvement of PPTN intrinsic connections in the modulation of pain, during tonic-clonic seizures. These results showed that the PPTN may be crucially involved in the neural network that organizes the post-ictal analgesia., (© 2014 Wiley Periodicals, Inc.)

Hippocampal theta activity is linked to various processes, including locomotion, learning and memory, and defense and affect (i.e., fear and anxiety). Interestingly, all classes of clinically effective anxiolytics, as well as experimental compounds that decrease anxiety in pre-clinical animal models of anxiety, reduce the frequency of hippocampal theta activity elicited by stimulation of the reticular formation in freely behaving or anesthetized animals. In the present experiments, we found that bilateral histamine infusions (0.5 µg/hemisphere) into the lateral septum (LS) of rats decreased anxiety-like responses in two models of anxiety, the elevated plus maze and novelty-induced suppression of feeding test. Surprisingly, these same infusions significantly increased hippocampal theta frequency elicited by reticular stimulation in urethane-anesthetized rats. In contrast to these findings, additional experiments showed that the clinically effective anxiolytic buspirone (40 mg/kg, i.p.) reduced theta frequency, confirming previous observations. Taken together, the dissociation of behavioral anxiolysis and theta frequency reduction noted here suggest that hippocampal theta frequency is not a direct index of anxiety levels in rodents. Further, the mechanisms underlying the behavioral and physiological effects elicited by histamine in the LS require further study., (© 2014 Wiley Periodicals, Inc.)

OBJECTIVE The authors sought to determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors. METHOD Data were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low-risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal pathways and the splenium and genu of the corpus callosum. RESULTS Visual orienting latencies were longer in 7-month-old infants who expressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD. CONCLUSIONS Flexibly and efficiently orienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis.

The corticoreticular pathway (CRP) innervates mainly the proximal muscles of extremities. Identification of the CRP by diffusion tensor tractography (DTT) in the human brain has recently become possible. However, little is known about the relation between proximal weakness and injury of the CRP in stroke patients. In this study, we attempted to investigate the usefulness of DTT for elucidation of the relation between proximal motor weakness and injury of the CRP in patients with cerebral infarct. Among 247 consecutive patients with cerebral infarct, four hemiparetic patients who showed more severe weakness in proximal joints (shoulder and hip) than distal joints (finger and ankle) of the affected extremities were recruited for this study. Evaluation of motor function, DTT, and transcranial magnetic stimulation (TMS) for evaluation of the corticospinal tract state by analysis of the characteristics of the motor-evoked potential were performed at the early stage of cerebral infarct (mean: 17.0 days; range: 11-29). The integrity of the CST on DTT findings in the affected hemisphere was preserved in all four patients and TMS findings in terms of latency and amplitude showed within normal range (one patient) and partial injuries (three patients) of the corticospinal tract. By contrast, on DTT of the CRP in the affected hemispheres, we observed Wallerian degeneration in two patients and discontinuations at infarct level in two patients. The injury of the CRP appeared to attribute the proximal weakness of the shoulder and hip observed in these four patients. Therefore, DTT of the CRP would be useful for elucidating the relation between proximal weakness and injury of the CRP in patients with cerebral infarct., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

This review considers recent evidence showing that cells in the reticular activating system (RAS) exhibit (1) electrical coupling mainly in GABAergic cells, and (2) gamma band activity in virtually all of the cells. Specifically, cells in the mesopontine pedunculopontine nucleus (PPN), intralaminar parafascicular nucleus (Pf), and pontine dorsal subcoeruleus nucleus dorsalis (SubCD) (1) show electrical coupling, and (2) all fire in the beta/gamma band range when maximally activated, but no higher. The mechanism behind electrical coupling is important because the stimulant modafinil was shown to increase electrical coupling. We also provide recent findings demonstrating that all cells in the PPN and Pf have high threshold, voltage-dependent P/Q-type calcium channels that are essential to gamma band activity. On the other hand, all SubCD, and some PPN, cells manifested sodium-dependent subthreshold oscillations. A novel mechanism for sleep-wake control based on transmitter interactions, electrical coupling, and gamma band activity is described. We speculate that continuous sensory input will modulate coupling and induce gamma band activity in the RAS that could participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Agrypnia (from the Greek: to chase sleep) excitata (AE) is a syndrome characterized by loss of sleep and permanent motor and autonomic hyperactivation (excitata). Disruption of the sleep-wake rhythm consists in the disappearance of spindle-delta activities, and the persistence of stage 1 non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep persists but fails to stabilize, appearing in short recurrent episodes, isolated, or mixed with stage 1 NREM sleep. Diurnal and nocturnal motor, autonomic and hormonal overactivity is the second hallmark of AE. Of particular interest is the finding that norepinephrine secretion is extremely elevated at all hours of the day and night whereas the nocturnal melatonin peak is lacking. Oneiric stupor is probably an exclusive sign of AE and consists in the recurrence of stereotyped gestures mimicking simple daily life activities. Agrypnia excitata aptly defines 3 different clinical conditions, fatal familial insomnia (FFI), an autosomal dominant prion disease, Morvan syndrome (MS), an autoimmune encephalitis, and delirium tremens (DT), the alcohol withdrawal syndrome. Agrypnia excitata is due to an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. This pathogenetic mechanism is visceral thalamus degeneration in FI, whereas it may depend on autoantibodies blocking voltage-gated potassium (VGK) channels within the limbic system in MS, and in the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in DT.

Background: The etiology of overactive bladder (OAB) remains unclear. Observed neurogenic factors in the literature are limited to suprapontine or spinal pathologies. The blink reflex is a useful tool in the evaluation of brainstem functions. Blink reflex latency times were evaluated in order to reveal pathology in the brainstem., Methods: A total of 60 women, 30 patients with idiopathic OAB and 30 healthy controls, were enrolled in the study. Blink reflex latency times were analyzed by electrical stimulation of the supraorbital nerve. Two responses in the orbicularis oculi muscle, early ipsilateral response (R1) and late bilateral response (R2) latency times, were recorded., Results: Mean ages of the patients and controls were 51.9 ± 5.3 and 49.2 ± 6.2 years, respectively. R2 latency times were significantly higher in patients than in controls. However, R1 latency times were similar between the two groups., Conclusions: The results of the study suggest a significant relation between late blink latency times and OAB. An oligosynaptic path via the trigeminal nuclei is responsible for R1; however, R2 response is relayed through the reticular formation. Stimulation of pontine reticular formation inhibits micturition contraction. In some patients, idiopathic OAB may result from reticular formation-originated pathology. Additional studies on other reticular formation-mediated reflexes are needed to reveal possible dysfunction of reticular formation., (Copyright © 2013 S. Karger AG, Basel.)

Background: Vegetative state (VS) is a complex condition that represents a challenging frontier for medicine and neuroscience research. Nowadays there is no scientifically validated treatment for VS patients, and their chronic long-term assistance is very demanding for healthcare systems worldwide., Objectives: The present paper is a systematic review of the role of spinal cord stimulation (SCS) as a treatment of patients with VS., Methods: Published literature on this topic was analyzed systematically. Clinical and epidemiological characteristics of VS, present therapeutic options and social costs of VS were also evaluated., Results: Only 10 papers have been published since 1988, and overall 308 VS patients have been treated with SCS worldwide; 51.6% displayed a clinical improvement and an amelioration of the environmental interaction. These effects are probably mediated by the stimulation of the reticular formation-thalamus-cortex pathway and by cerebral blood flow augmentation induced by SCS., Conclusions: The experience on this topic is still very limited, and on this basis it is still hard to make any rigorous assessment. However, the most recent experiments represent significant progress in the research on this topic and display SCS as a possible therapeutic tool in the treatment of VS., (Copyright © 2013 S. Karger AG, Basel.)

The effect of reticular formation excitability on maximum voluntary torque (MVT) generation and associated muscle activation at the shoulder and elbow was investigated through natural elicitation (active head rotation) of the asymmetric tonic neck reflex (ATNR) in 26 individuals with stroke and 9 age-range-matched controls. Isometric MVT generation at the shoulder and elbow was quantified with the head rotated (face pointing) contralateral and ipsilateral to the paretic (stroke) and dominant (control) arm. Given the dominance of abnormal torque coupling of elbow flexion with shoulder abduction (flexion synergy) in stroke and well-developed animal models demonstrating a linkage between reticular formation and ipsilateral elbow flexors and shoulder abductors, we hypothesized that constituent torques of flexion synergy, specifically elbow flexion and shoulder abduction, would increase with contralateral head rotation. The findings of this investigation support this hypothesis. Increases in MVT for three of four flexion synergy constituents (elbow flexion, shoulder abduction, and shoulder external rotation) were observed during contralateral head rotation only in individuals with stroke. Electromyographic data of the associated muscle coactivations were nonsignificant but are presented for consideration in light of a likely underpowered statistical design for this specific variable. This study not only provides evidence for the reemergence of ATNR following stroke but also indicates a common neuroanatomical link, namely, an increased reliance on ipsilateral reticulospinal pathways, as the likely mechanism underlying the expression of both ATNR and flexion synergy that results in the loss of independent joint control.

In the decade since the discovery that pathology of the orexin/hypocretin system is causative for the sleep disorder narcolepsy, considerable progress has been made in understanding the functional role of the neuropeptide. Two, apparently separate functions of orexin have emerged as a consensus from studies to date. The first is the effect on vigilance state boundaries, as exemplified by narcolepsy. Thus the absence of orexin severely limits the ability to maintain prolonged periods of wakefulness or sleep and also allows the unregulated appearance of cataplexy as sudden muscle weakness during wakefulness. The second function is that orexin acts as a signaling molecule in transferring information about physiological disequilibrium to the central nervous system. Orexin activates the central arousal and motor systems during such disequilibrium and so may facilitate the necessary response and adaptation to restore equilibrium. A feasible relationship between these two functions is therefore that the maintenance of prolonged and active wakefulness is an integral part of this adaptive process. Furthermore, the limit placed on the onset of sleep by orexin suggests that these adaptive processes then continue during sleep to become integrated into the development of a coping strategy for the longer term., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Preclinical evidence suggests that opioid withdrawal induces central sensitization (CS) that is maintained by supraspinal contributions from the descending pain modulatory system (DPMS). Here, in healthy human subjects we use functional magnetic resonance imaging to study the supraspinal activity during the withdrawal period of the opioid remifentanil. We used a crossover design and thermal stimuli on uninjured skin to demonstrate opioid withdrawal-induced hyperalgesia (OIH) without a CS-inducing peripheral stimulus. Saline was used in the control arm to account for effects of time. OIH in this injury-free model was observed in a subset of the healthy subjects (responders). Only in these subjects did opioid infusion and withdrawal induce a rise in activity in the mesencephalic-pontine reticular formation (MPRF), an area of the DPMS that has been previously shown to be involved in states of CS in humans, which became significant during the withdrawal phase compared with nonresponders. Paradoxically, this opioid withdrawal-induced rise in MPRF activity shows a significant negative correlation with the behavioral OIH score indicating a predominant inhibitory role of the MPRF in the responders. These data illustrate that in susceptible individuals central mechanisms appear to regulate the expression of OIH in humans in the absence of tissue injury, which might have relevance for functional pain syndromes where a peripheral origin for the pain is difficult to identify.

Little is known regarding the descending inhibitory control of genital reflexes such as ejaculation and vaginal contractions. The brainstem nucleus paragigantocellularis (nPGi) projects bilaterally to the lumbosacral motoneuron pools that innervate the genital musculature of both male and female rats. Electrolytic nPGi lesions facilitate ejaculation in males, leading to the hypothesis that the nPGi is the source of descending inhibition to genital reflexes. However, the function of the nPGi in female sexual behavior remains to be elucidated. To this end, male and female rats received bilateral excitotoxic fiber-sparing lesions of the nPGi, and sexual behavior and sexual behavior-induced Fos expression were examined. In males, nPGi lesions facilitated copulation, supporting the hypothesis that the nPGi, and not fibers-of-passage, is the source of descending inhibition of genital reflexes in male rats. nPGi lesions in males did not alter sexual behavior-induced Fos expression in any brain region examined. nPGi-lesioned females spent significantly less time mating with stimulus males and had significantly longer ejaculation-return latencies compared to baseline. These results did not significantly differ from control females, but this trend warranted further analysis of the reinforcing value of sexual behavior. Both lesioned and non-lesioned females formed a conditioned place preference (CPP) for artificial vaginocervical stimulation (aVCS). However, post-reinforcement, nPGi-lesioned females did not differ in the percentage of time spent in the non-reinforced chamber versus the reinforced chamber, suggesting a weakened CPP for aVCS. nPGi lesions in females reduced sexual behavior-induced Fos expression throughout the hypothalamus and amygdala. Taken together, these results suggest that while nPGi lesions in males facilitate copulation, such lesions in females attenuate several aspects of sexual behavior resulting in a reduction in the rewarding value of copulation that may be mediated by nPGi control of genital reflexes. This work has important implications for the understanding and treatment of sexual dysfunction in people including delayed/premature ejaculation, involuntary vaginal spasms, and pain during intercourse., (Published by Elsevier Ltd.)

Neurons in the caudalmost ventrolateral medulla (cmVLM) respond to noxious stimulation. We previously have shown most efferent projections from this locus project to areas implicated either in the processing or modulation of pain. Here we show the cmVLM of the rat receives projections from superficial laminae of the medullary dorsal horn (MDH) and has neurons activated with capsaicin injections into the temporalis muscle. Injections of either biotinylated dextran amine (BDA) into the MDH or fluorogold (FG)/fluorescent microbeads into the cmVLM showed projections from lamina I and II of the MDH to the cmVLM. Morphometric analysis showed the retrogradely-labeled neurons were small (area 88.7 µm(2)±3.4) and mostly fusiform in shape. Injections (20-50 µl) of 0.5% capsaicin into the temporalis muscle and subsequent immunohistochemistry for c-Fos showed nuclei labeled in the dorsomedial trigeminocervical complex (TCC), the cmVLM, the lateral medulla, and the internal lateral subnucleus of the parabrachial complex (PBil). Additional labeling with c-Fos was seen in the subnucleus interpolaris of the spinal trigeminal nucleus, the rostral ventrolateral medulla, the superior salivatory nucleus, the rostral ventromedial medulla, and the A1, A5, A7 and subcoeruleus catecholamine areas. Injections of FG into the PBil produced robust label in the lateral medulla and cmVLM while injections of BDA into the lateral medulla showed projections to the PBil. Immunohistochemical experiments to antibodies against substance P, the substance P receptor (NK1), calcitonin gene regulating peptide, leucine enkephalin, VRL1 (TPRV2) receptors and neuropeptide Y showed that these peptides/receptors densely stained the cmVLM. We suggest the MDH- cmVLM projection is important for pain from head and neck areas. We offer a potential new pathway for regulating deep pain via the neurons of the TCC, the cmVLM, the lateral medulla, and the PBil and propose these areas compose a trigeminoreticular pathway, possibly the trigeminal homologue of the spinoreticulothalamic pathway.

The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45-60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs.

Objective: The ascending reticular activating system (ARAS) modulates circadian wakefulness, which is preserved in a persistent vegetative state (PVS). Its metabolism is preserved. Impairment of metabolism in the polymodal associative cortices (i.e., precuneus) is characteristic of PVS where awareness is abolished. Because the interaction of these 2 structures allows conscious sensory perception, our hypothesis was that an impaired functional connectivity between them participates in the loss of conscious perception., Methods: (15)O-radiolabeled water PET measurement of regional cerebral blood flow (rCBF) was performed at rest and during a proprioceptive stimulation. Ten patients in PVS and 10 controls were compared in a cross-sectional study. The functional connectivity from the primary sensorimotor cortex (S1M1) and the ARAS in both groups was also investigated., Results: Compared with controls, patients showed significantly less rCBF in posterior medial cortices (precuneus) and higher rCBF in ARAS at rest. During stimulation, bilateral Brodmann area 40 was less activated and not functionally correlated to S1M1 in PVS as it was in controls. Precuneus showed a lesser degree of deactivation in patients. Finally, ARAS whose activity was functionally correlated to that of the precuneus in controls was not in PVS., Conclusions: Global neuronal workspace theory predicts that damage to long-distance white matter tracts should impair access to conscious perception. During persistent vegetative state, we identified a hypermetabolism in the ascending reticular activating system (ARAS) and impaired functional connectivity between the ARAS and the precuneus. This result emphasizes the functional link between cortices and brainstem in the genesis of perceptual awareness and strengthens the hypothesis that consciousness is based on a widespread neural network.

The present study describes at the ultrastructural level the hypocretinergic innervation of brainstem reticular formation neurons that project to the medial frontal cortex in the rat. In addition, we assess, by using dual immunofluorescence techniques, the proportion of those reticular neurons containing specific neurotransmitters. Our results indicate that hypocretinergic axons make asymmetric synapses with neurons within the locus coeruleus, ventral tegmental area, dorsal raphe nucleus and laterodorsal tegmental nucleus that target the medial frontal cortex, Hypocretins could facilitate wakefulness and cortical activation, therefore, by activation of those neurons with cortical projections in these four reticular nuclei.

Ocular flutter is a relatively rare eye movement disorder characterized by intermittent bursts of conjugate horizontal saccades without an intersaccadic interval. Its anatomical and neurophysiological basis remains controversial. Here we present a case of ocular flutter in which the flutter declined as the clinical stage of the associated ailment declined, until it eventually disappeared. Radiological examination revealed a tiny lesion in the right upper pontine tegmentum that included areas of the reticular formation, superior cerebellar peduncle and locus ceruleus. Because the lesion occupied the upper part of the paramedian pontine reticular formation, it did not contain omnipause neurons, which would seem to contradict a previously hypothesized explanation for ocular flutter: loss of pause cell control over saccadic burst neurons. On the other hand, we found no lesion in the area of the deep cerebellar nuclei; instead, the lesion was in the path of the projection from the fastigial nucleus to the brainstem saccadic generator. This is consistent with the idea that, in this case, there is impaired control by the cerebellar fastigial nucleus, especially of the horizontal saccadic system.

Background: The impairment of the pontine reticular formation (PRF) has recently been revealed to be histopathologically connected with focal-cortical seizure induced generalized convulsive status epilepticus. To elucidate whether the impairment of the PRF is a general phenomenon during status epilepticus, the focal-cortical 4-aminopyridine (4-AP) application was compared with other epilepsy models. The presence of "dark" neurons in the PRF was investigated by the sensitive silver method of Gallyas in rats sacrificed at 3 h after focal 4-AP crystal or systemic 4-AP, pilocarpine, or kainic acid application. The behavioral signs of the developing epileptic seizures were scored in all rats. The EEG activity was recorded in eight rats., Results: Regardless of the initiating drug or method of administration, "dark" neurons were consistently found in the PRF of animals entered the later phases of status epilepticus. EEG recordings demonstrated the presence of slow oscillations (1.5-2.5 Hz) simultaneously with the appearance of giant "dark" neurons in the PRF., Conclusion: We argue that the observed slow oscillation corresponds to the late periodic epileptiform discharge phase of status epilepticus, and that the PRF may be involved in the progression of status epilepticus.

It is unclear how the torticollis occasionally observed in patients with progressive supranuclear palsy (PSP) relates to vestibulo-collic reflex mechanisms. We report here the results of vestibular evoked myogenic potentials (VEMPs) in a PSP patient with forced head deviation in the opposite direction of turning, leading to torticollis for a few seconds. As VEMPs were normal bilaterally we conclude that an enhanced vestibulo-collic reflex per se is not the cause of the torticollis in our patient. The abnormal head deviation induced by turning in some PSP patients is best explained by damage to reticular nuclei responsible for resetting eye and head saccades. When such mechanisms are defective, unopposed vestibulo-collic reflexes can lead to eye and head deviations in the opposite direction of body turns.

The Roundabout (Robo) family of receptors and their Slit ligands play well-established roles in axonal guidance, including in humans where horizontal gaze palsy with progressive scoliosis (HGPPS) is caused by mutations in the robo3 gene. Although significant progress has been made toward understanding the mechanism by which Robo receptors establish commissural projections in the central nervous system, less is known about how these projections contribute to neural circuits mediating behavior. In this study, we report cloning of the zebrafish behavioral mutant twitch twice and show that twitch twice encodes robo3. We show that in mutant hindbrains the axons of an identified pair of neurons, the Mauthner cells, fail to cross the midline. The Mauthner neurons are essential for the startle response, and in twitch twice/robo3 mutants misguidance of the Mauthner axons results in a unidirectional startle response. Moreover, we show that twitch twice mutants exhibit normal visual acuity but display defects in horizontal eye movements, suggesting a specific and critical role for twitch twice/robo3 in sensory-guided behavior.

Study Design: Compact literature review to provide basic knowledge of the reticular formation (RF) for clinicians., Setting: United Kingdom., Materials and Methods: The anatomical findings were collected from very recently published and well-edited books on neuroscience instead of hundreds of articles that contain materials still requiring test of time and difficult for busy clinicians to digest. Other individual references on specific issues such as a micturition centre, source of sildenafil citrate and so on are added. Clinical considerations discuss commonly encountered problems of spinal cord injury service and science. Every clinical condition is discussed in conjunction with the anatomy and physiology of the RF., Results: This section involves anatomy. (1) The core RF is located in the brain stem. The RF proper is divided into three longitudinal zones: the lateral (sensory), the medial (motor) and the midline (all others) zone. The midline zone is essential for wakefulness and consciousness. (2) Other brain stem structures sharing functions of the RF proper: periaqueductal grey (PAG), red nuclei, inferior olivary nucleus and precerebellar nucleus. PAG is almost related to all functions of the central nervous system, whereas the others are more connected to cerebellar functions of movements. (3) Spinal cord RF is located in the intermediolateral zone. It sends ascending and receives descending signals to coordinate and modulate motor, sensory and other functions., Discussion: This section involves clinical consideration. Multisystem damage, muscle contraction, upper urinary tract, sexual behaviour, skin trophic, pain, sleep apnoea, cross-system damages, spinal cord repair and comprehensive management are discussed to enlighten the clinical importance of the RF.

Sleep disturbances are widespread among older adults. Degenerative neurologic disorders that cause dementia, such as Alzheimer's disease and Parkinson's disease, exacerbate age-related changes in sleep, as do many common comorbid medical and psychiatric conditions. Medications used to treat chronic illness and insomnia have many side effects that can further disrupt sleep and place patients at risk for injury. This article reviews the neurophysiology of sleep in normal aging and sleep changes associated with common dementia subtypes and comorbid conditions. Current pharmacologic and nonpharmacologic evidence-based treatment options are discussed, including the use of light therapy, increased physical and social activity, and multicomponent cognitive-behavioral interventions for improving sleep in institutionalized and community-dwelling adults with dementia.

Background and Purpose: Experimental studies suggested neurovascular compression of the brain stem as a cause of hypertension. The aim of our prospective study was to investigate the effect of microvascular decompression in patients with severe hypertension with neurovascular compression on blood pressure and central sympathetic nerve activity in the long-term., Methods: Fourteen patients (4 males; mean age, 46+/-8 years) with essential hypertension underwent microvascular decompression of the brain stem. Vasoconstrictor muscle sympathetic nerve activity (recorded by microneurography: burst frequency, bursts/min) and blood pressure (24-hour profiles) were investigated before surgery and 7 days, 3 months, and every 6 months postoperatively., Results: Muscle sympathetic nerve activity was preoperatively elevated and decreased significantly postoperatively (35+/-13 bursts/min vs 20+/-9 bursts/min; P<0.01). Sympathetic activity remained reduced 3 months (19+/-8 bursts/min; P<0.01), 6 months (19+/-7 bursts/min; P<0.01), and 12 months (23+/-9 bursts/min; P<0.01) postoperatively. However, in the long-term, sympathetic nerve activity increased again (18 months after surgery: 28+/-10 bursts, not significant; 24 months postoperatively: 34+/-12 bursts/min, not significant). Systolic and diastolic blood pressure decreased from 162+/-6/98+/-5 mm Hg preoperatively to 133+/-6/85+/-4 mm Hg (7 days postoperatively; P<0.01); 136+/-5/86+/-4 mm Hg (3 months postoperatively; P<0.01); 132+/-4/85+/-4 mm Hg (6 months postoperatively; P<0.01); 132+/-3/85+/-5 mm Hg (12 months postoperatively; P<0.01); 132+/-5/84+/-5 mm Hg; P<0.01). Twenty-four months after microvascular decompression, blood pressure increased again up to 158+/-7/96+/-6 mm Hg, corresponding to the sympathetic nerve activity course., Conclusions: Sympathetic nerve activity and blood pressure are temporary reduced by microvascular decompression in patients with severe hypertension with neurovascular compression. The data are a hint for sympathetic overactivity as a pathomechanism in this subgroup of patients.

A 62-year-old woman with relapsing-remitting multiple sclerosis suddenly complained of diplopia associated with bilateral adduction impairment, nystagmus of the abducting eye bilaterally, and sparing of abduction, convergence, and vertical eye movements, consistent with bilateral internuclear ophthalmoplegia. Within 1 week, she had developed a complete horizontal gaze paralysis even with the oculocephalic maneuver. Vertical saccades were slow and convergence was preserved. There was a right lower motor neuron seventh cranial nerve palsy. Brain MRI showed a new enhancing lesion involving the pontine tegmentum. Clinical and MRI follow-up showed recovery after 6 months. The slowing of vertical saccades may have been due to spread of the demyelinating lesion to the adjacent paramedian pontine reticular formation, which contains omnipause neurons lying in the raphe interpositus nucleus thought to inhibit excitatory burst neurons for horizontal and vertical saccades. Our patient verifies the fact that vertical saccadic abnormalities may occur from a lesion apparently confined to the pons.

The involvement of reactive oxygen species such as superoxide is implicated in the pathogenesis of hypertension. The brain contains a high concentration of polyunsaturated fatty acids in its cell membranes. These fatty acids are targets of oxygen-derived free radicals. Thiobarbituric acid-reactive substances (TBARS), an indirect marker of oxidative stress, are increased in the brainstem of stroke-prone spontaneously hypertensive rats (SHRSP) compared with those of Wistar-Kyoto rats (WKY). In addition, the intensity of electron spin resonance signals taken from the rostral ventrolateral medulla (RVLM), a cardiovascular center, decreases more rapidly in SHRSP than in WKY. To confirm the role of reactive oxygen species in the RVLM or the nucleus tractus solitarius (NTS) in SHRSP, we transfected adenovirus vectors encoding the manganese superoxide dismutase (MnSOD) gene (AdMnSOD) or Cu/Zn-SOD gene (AdCu/ZnSOD) bilaterally into the RVLM or the NTS. After the gene transfer, blood pressure and heart rate of SHRSP, monitored by radio-telemetry system, were significantly decreased compared with non-treated SHRSP, but not WKY. Urinary norepinephrine excretion was significantly decreased in AdMnSOD- or AdCu/ZnSOD-transfected SHRSP, but not in WKY. Furthermore, we found that activation of NAD(P)H oxidase via Rac1 is a source of reactive oxygen species generation in the brain of hypertensive rats. Taken together, these results suggest that the increased oxidative stress in the RVLM and the NTS contribute to the central nervous system mechanisms underlying hypertension in SHRSP. We also found that atorvastatin has actions of reducing oxidative stress in the brain associated with sympatho-inhibitory effects.

In a previous study using male rats, a correlation was found between the development of "at-level" allodynia in T6-7 dermatomes following severe T8 spinal contusion injury and the sparing of some myelinated axons within the core of the lesion epicenter. To further test our hypothesis that this sparing is important for the expression of allodynia and the supraspinal plasticity that ensues, an injury that severs all axons (i.e., a complete spinal cord transection) was made in 15 male rats. Behavioral assessments were done at level throughout the 30-day recovery period followed by terminal electrophysiological recordings (urethane anesthesia) from single medullary reticular formation (MRF) neurons receiving convergent nociceptive inputs from receptive fields above, at, and below the lesion level. None of the rats developed signs of at-level allodynia (versus 18 of 26 male rats following severe contusion). However, the terminal recording (206 MRF neurons) data resembled those obtained previously post-contusion. That is, there was evidence of neuronal hyper-excitability (relative to previous data from intact controls) to high- and low-threshold mechanical stimulation for "at-level" (dorsal trunk) and "above-level" (eyelids and face) cutaneous territories. These results, when combined with prior data on intact controls and severe/moderate contusions, indicate that (1) an anatomically incomplete injury (some lesion epicenter axonal sparing) following severe contusion is likely important for the development of allodynia and (2) the neuronal hyper-excitability at the level of the medulla is likely involved in nociceptive processes that are not directly related to the conscious expression of pain-like avoidance behaviors that are being used as evidence of allodynia.

Changes in the mRNA expression of neurotransmitters receptors under chronic pain conditions have been described in various areas of the central nervous system (CNS). Delta opioid receptors (DORs) have been implicated in pain mechanisms but, although its mRNA expression has been studied in the rat CNS, there are no reports describing its distribution in specific thalamic and brainstem nuclei during chronic inflammatory pain. Here, in situ hybridization for DOR mRNA was performed in brain sections from control and monoarthritic (MA) rats with 2, 4, 7 and 14 days of inflammation. Grain densities were determined bilaterally in the ventrobasal complex (VB), posterior (Po), centromedial/centrolateral (CM/CL) and reticular (Rt) nuclei of the thalamus, and in the dorsal reticular (DRt), lateral reticular (LRt) and parvocellular reticular (PCRt) nuclei of the brainstem. Control animals exhibited weak mRNA expression in the VB, Po and CM/CL, as well as in PCRt, while moderate grain densities were observed in the Rt, DRt and LRt. During MA, DOR mRNA expression was significantly decreased (22%) in the Rt contralateral to the affected joint at both 7 and 14 days of inflammation, as compared to controls. A bilateral reduction (35%) was also observed in the DRt at 14 days of MA, while a contralateral increase was found in the PCRt at 7 days (+39%). No significant changes were observed in the other regions analyzed. Thus, data show changes in the DOR mRNA expression during the development of chronic inflammatory pain, in thalamic and brainstem nuclei implicated in pain processing mechanisms.

A 51-year-old man developed positional vertigo, ataxia, dysgeusia, diplopia, and oscillopsia. Eye movement examination and video-oculographic recording disclosed primary position upbeat nystagmus (PPUN) and a right internuclear ophthalmoplegia. Brain MRI showed a small focal lesion in the right dorsal tegmentum of the caudal pons with signal characteristics consistent with a primary demyelinating central nervous system disease. PPUN has not been described previously with a lesion in such a location. Clinicoanatomic correlation in this patient suggests that a lesion of the superior vestibular nucleus and its efferent crossing ventral tegmental tract could be responsible for the PPUN. This case report contributes to a better understanding of the role of this pathway in humans.

EMS providers frequently encounter patients who are not alert and present with an altered mental status, meaning their level of brain function is in question. Various physical examination techniques are employed during the assessment to determine the level of cerebral function and integrity of the brainstem. It is important to understand the limitations of these techniques, as well as potential findings that may cause you to erroreously interpret, re port and document the level of brain function. This information is often used to identify trends to determine if the patient's condition is deteriorating, remaining the same or improving.

A total of 77 patients with panic attacks (PA) with and without agoraphobic disorders were studied, along with 28 healthy subjects. Use of clinical-neurological investigation methods was supplemented by psychological methods, EEG recordings, and auditory event-linked evoked potentials (EP). Patients with PA with agoraphobic disorders were found to be characterized by significant decreases in the power density of the alpha rhythm and increases in the power density of the beta rhythm in the right hemisphere, reflecting significant activation of the ascending mesencephalic reticular formation; the most characteristic feature in patients without agoraphobia was a significant increase in the power density of the theta rhythm in the temporal areas of the right hemisphere, reflecting increased activity in temporal-limbic structures. Patients with agoraphobia had lower EP P300 peak amplitudes, with more significant impairments to habituation, and more marked impairments of attention and higher levels of anxiety and depression as compared with patients without agoraphobia.

Objective: Central nervous system reorganization following spinal cord injury (SCI) may cause functional changes in the motor tracts in patients in whom increased auditory startle responses (ASRs) have been previously reported. We hypothesized that if increased ASRs in patients with incomplete SCI were due to compensatory mechanisms, these changes would be related to severity and/or localization of the lesion., Methods: We examined ASR characteristics in 29 SCI patients and 14 age-matched healthy volunteers. Fourteen patients had incomplete and 15 complete SCI; 10 patients had cervical and 19 thoracolumbar SCI. Five auditory stimuli were applied binaurally to subjects in a sitting position, with a 5-min interstimulus interval. Surface electromyographic recordings were obtained from orbicularis oculi (OOc), sternocleidomastoid (SCM), biceps brachii (BB), and tibialis anterior (TA) muscles., Results: ASR probability was significantly higher and area-under-the-curve was significantly larger in SCM and BB in patients than in controls. ASR latency was significantly shorter in SCM and BB in patients with cervical than in those with thoracolumbar SCI (p < 0.02), but there were no statistically significant differences between complete and incomplete SCI (p > 0.1). Time span since onset correlated significantly with ASR area in OOc, SCM and BB (p < 0.05)., Conclusion: The capability of the adult central nervous system to reorganize its circuits over time for improved functionality following injury is probably the key to understanding the increased ASRs in patients with SCI. The exaggeration of the startle reflex is potentially important since it may be useful for augmenting voluntary movement in the clinical rehabilitation of patients with SCI.