Responses evoked by electrical stimulation of the brainstem reticular formation in the jaw-opening and hypoglossal motor nerves of an arterially perfused rat preparation.

The interneuronal system in the brainstem reticular formation plays an important role in elaborate muscle coordination during various orofacial motor behaviors. In this study, we examined the distribution in the brainstem reticular formation of the sites that induce monosynaptic motor activity in the mylohyoid (jaw-opening) and hypoglossal nerves using an arterially perfused rat preparation. Electrical stimulation applied to 286 and 247 of the 309 sites in the brainstem evoked neural activity in the mylohyoid and hypoglossal nerves, respectively. The mean latency of the first component in the mylohyoid nerve response was significantly shorter than that in the hypoglossal nerve response. Moreover, the latency histogram of the first component in the hypoglossal nerve responses was bimodal, which was separated by 4.0 ms. The sites that induced short-latency (<4.0 ms) motor activity in the mylohyoid nerve and the hypoglossal nerve were frequently distributed in the rostral portion and the caudal portion of the brainstem reticular formation, respectively. Such difference in distributions of short-latency sites for mylohyoid and hypoglossal nerve responses likely corresponds to the distribution of excitatory premotor neurons targeting mylohyoid and hypoglossal motoneurons.

Wernekink Commissure Syndrome: A Rare Cause of Bilateral Cerebellar Syndrome.

PURPOSE: Focal signs are a big deal in neurology and are among the most important clues leading to diagnosis and localization. Wernekink commissure syndrome is due to lesions in the caudal paramedian midbrain involving the entire decussation of the superior cerebellar peduncles, resulting in the clinical hallmark of a bilateral cerebellar syndrome. CASE REPORT: A 79-year-old man presented with sudden, severe unsteadiness associated with slurring of speech, binocular double vision, and bilateral hand tremor. Examination showed right INO, moderately severe dysarthria, bilateral dysmetria and dysdiadochokinesia, with severe truncal ataxia and bilateral upper and lower limb ataxia. Also, bilateral coarse tremor was noted in both hands which was present at rest, action and on reaching for objects. Brain MRI revealed an acute infarction involving the Wernekinck decussation in the right caudal midbrain and mesencephalo-pontine junction. CONCLUSION: The differential of Wernekink Commissure Syndrome is complex, and localization and lateralization are extremely difficult owing to prominent bilateral cerebellar symptoms. The finding of an associated unilateral INO in some cases makes it possible to confidently narrow the list of differentials and localize the lesion to the paramedian tegmentum ipsilateral to the non-adducting eye.

Difference between injuries of the corticospinal tract and corticoreticulospinal tract in patients with diffuse axonal injury: a diffusion tensor tractography study.

Objectives: No studies have investigated differences in injury of the corticospinal tract (CST) and corticoreticulospinal tract (CRT) following diffuse axonal injury (DAI) to date. Therefore, we investigated differences in injury of the CST and CRT in patients with DAI using diffusion tensor tractography (DTT).Methods: Twenty consecutive patients with DAI and 20 control subjects were recruited. CST and CRT were reconstructed. Each part of the CST and CRT was analyzed in terms of DTT parameters and configuration.Results: Upon group analysis, decreased FA and TV values were observed in both the CST and CRT in the patient group compared with the control group (%) (p < .05). In the individual analysis in terms of the TV, significantly higher injury incidence was observed for the CRT (47.5%) than the CST (25.0%) (p < .05). Evaluation of the DTT configuration revealed significantly higher injury incidence for the CRT (50.0%) than the CST (17.5%) (p < .05). Specifically, the incidence of discontinuation was significantly higher for the CRT (40.0%) than the CST (10.0%) (p < .05).Conclusions: Injury of the CST and CRT was detected in patients with DAI using DTT. In terms of the incidence and severity of neural injury, the CRT appeared to be more vulnerable to DAI than the CST.

Imbalanced Corticospinal and Reticulospinal Contributions to Spasticity in Humans with Spinal Cord Injury.

Damage to the corticospinal and reticulospinal tract has been associated with spasticity in humans with upper motor neuron lesions. We hypothesized that these descending motor pathways distinctly contribute to the control of a spastic muscle in humans with incomplete spinal cord injury (SCI). To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the leg representation of the primary motor cortex, maximal voluntary contractions (MVCs), and the StartReact response (shortening in reaction time evoked by a startling stimulus) in the quadriceps femoris muscle in male and females with and without incomplete SCI. A total of 66.7% of the SCI participants showed symptoms of spasticity, whereas the other 33.3% showed no or low levels of spasticity. We found that participants with spasticity had smaller MEPs and MVCs and larger StartReact compared with participants with no or low spasticity and control subjects. These results were consistently present in spastic subjects but not in the other populations. Clinical scores of spasticity were negatively correlated with MEP-max and MVC values and positively correlated with shortening in reaction time. These findings provide evidence for lesser corticospinal and larger reticulospinal influences to spastic muscles in humans with SCI and suggest that these imbalanced contributions are important for motor recovery.SIGNIFICANCE STATEMENT Although spasticity is one of the most common symptoms manifested in humans with spinal cord injury (SCI) to date, its mechanisms of action remain poorly understood. We provide evidence, for the first time, of imbalanced contributions of the corticospinal and reticulospinal tract to control a spastic muscle in humans with chronic incomplete SCI. We found that participants with SCI with spasticity showed small corticospinal responses and maximal voluntary contractions and larger reticulospinal gain compared with participants with no or low spasticity and control subjects. These results were consistently present in spastic subjects but not in the other populations. We showed that imbalanced corticospinal and reticulospinal tract contributions are more pronounced in participants with chronic incomplete SCI with lesser recovery.

Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin.

The aim of this study was to investigate structural changes in the brain stem of adolescents with narcolepsy, a disorder characterized by excessive daytime sleepiness, fragmented night-time sleep, and cataplexy. For this purpose, we used quantitative magnetic resonance imaging to obtain R1 and R2 relaxation rates, proton density, and myelin maps in adolescents with narcolepsy (n = 14) and healthy controls (n = 14). We also acquired resting state functional magnetic resonance imaging (fMRI) for brainstem connectivity analysis. We found a significantly lower R2 in the rostral reticular formation near the superior cerebellar peduncle in narcolepsy patients, family wise error corrected p = .010. Narcolepsy patients had a mean R2 value of 1.17 s-1 whereas healthy controls had a mean R2 of 1.31 s-1, which was a large effect size with Cohen d = 4.14. We did not observe any significant differences in R1 relaxation, proton density, or myelin content. The sensitivity of R2 to metal ions in tissue and the transition metal ion chelating property of neuromelanin indicate that the R2 deviant area is one of the neuromelanin containing nuclei of the brain stem. The close proximity and its demonstrated involvement in sleep-maintenance, specifically through orexin projections from the hypothalamus regulating sleep stability, as well as the results from the connectivity analysis, suggest that the observed deviant area could be the locus coeruleus or other neuromelanin containing nuclei in the proximity of the superior cerebellar peduncle. Hypothetically, the R2 differences described in this paper could be due to lower levels of neuromelanin in this area of narcolepsy patients.

Changes of motor corticobulbar projections following different lesion types affecting the central nervous system in adult macaque monkeys.

Functional recovery from central nervous system injury is likely to be partly due to a rearrangement of neural circuits. In this context, the corticobulbar (corticoreticular) motor projections onto different nuclei of the ponto-medullary reticular formation (PMRF) were investigated in 13 adult macaque monkeys after either, primary motor cortex injury (MCI) in the hand area, or spinal cord injury (SCI) or Parkinson's disease-like lesions of the nigro-striatal dopaminergic system (PD). A subgroup of animals in both MCI and SCI groups was treated with neurite growth promoting anti-Nogo-A antibodies, whereas all PD animals were treated with autologous neural cell ecosystems (ANCE). The anterograde tracer BDA was injected either in the premotor cortex (PM) or in the primary motor cortex (M1) to label and quantify corticobulbar axonal boutons terminaux and en passant in PMRF. As compared to intact animals, after MCI the density of corticobulbar projections from PM was strongly reduced but maintained their laterality dominance (ipsilateral), both in the presence or absence of anti-Nogo-A antibody treatment. In contrast, the density of corticobulbar projections from M1 was increased following opposite hemi-section of the cervical cord (at C7 level) and anti-Nogo-A antibody treatment, with maintenance of contralateral laterality bias. In PD monkeys, the density of corticobulbar projections from PM was strongly reduced, as well as that from M1, but to a lesser extent. In conclusion, the densities of corticobulbar projections from PM or M1 were affected in a variable manner, depending on the type of lesion/pathology and the treatment aimed to enhance functional recovery.

Progressive recruitment of contralesional cortico-reticulospinal pathways drives motor impairment post stroke.

KEY POINTS: Activation of the shoulder abductor muscles in the arm opposite a unilateral brain injury causes involuntary increases in elbow, wrist and finger flexion in the same arm, a phenomenon referred to as the flexion synergy. It has been proposed that flexion synergy expression is related to reduced output from ipsilesional motor cortex and corticospinal pathways. In this human subjects study, we provide evidence that the magnitude of flexion synergy expression is instead related to a progressive, task-dependent recruitment of contralesional cortex. We also provide evidence that recruitment of contralesional cortex may induce excessive activation of ipsilateral reticulospinal descending motor pathways that cannot produce discrete movements, leading to flexion synergy expression. We interpret these findings as an adaptive strategy that preserves low-level motor control at the cost of fine motor control. ABSTRACT: A hallmark of hemiparetic stroke is the loss of fine motor control in the contralesional arm and hand and the constraint to a grouped movement pattern known as the flexion synergy. In the flexion synergy, increasing shoulder abductor activation drives progressive, involuntary increases in elbow, wrist and finger flexion. The neural mechanisms underlying this phenomenon remain unclear. Here, across 25 adults with moderate to severe hemiparesis following chronic stroke and 18 adults without neurological injury, we test the overall hypothesis that two inter-related mechanisms are necessary for flexion synergy expression: increased task-dependent activation of the intact, contralesional cortex and recruitment of contralesional motor pathways via ipsilateral reticulospinal projections. First, we imaged brain activation in real time during reaching motions progressively constrained by flexion synergy expression. Using this approach, we found that cortical activity indeed shifts towards the contralesional hemisphere in direct proportion to the degree of shoulder abduction loading in the contralesional arm. We then leveraged the post-stroke reemergence of a developmental brainstem reflex to show that anatomically diffuse reticulospinal motor pathways are active during synergy expression. We interpret this progressive recruitment of contralesional cortico-reticulospinal pathways as an adaptive strategy that preserves low-level motor control at the cost of fine motor control.

Hypersomnia due to injury of the ventral ascending reticular activating system following cerebellar herniation: A case report.

RATIONALE: We report on a patient with hypersomnia who showed injury of the lower ascending reticular activating system (ARAS) following cerebellar herniation due to a cerebellar infarct, detected on diffusion tensor tractography (DTT). PATIENT CONCERNS: A 53-year-old male patient was diagnosed as a left cerebellar infarct, and underwent decompressive suboccipital craniectomy due to brain edema at 2 days after the onset of a cerebellar infarct. Three weeks after onset when the patient started rehabilitation, he showed hypersomnia without impairment of consciousness; he fell asleep most of daytime without external stimulation and showed an abnormal score on the Epworth Sleepiness Scale: 15 (full score: 24, cut off for hypersomnia: 10). DIAGNOSES AND OUTCOMES: On 3-week DTT, narrowing of the upper portion of the lower ventral ARAS between the pontine reticular formation and the hypothalamus was observed on both sides. In addition, partial tearing was observed in the middle portion of the right lower ventral ARAS. LESSONS: In conclusion, we found injury of the lower ventral ARAS in a patient with hypersomnia following cerebellar herniation due to a cerebellar infarct.

Homeostatic Changes in GABA and Acetylcholine Muscarinic Receptors on GABAergic Neurons in the Mesencephalic Reticular Formation following Sleep Deprivation.

We have examined whether GABAergic neurons in the mesencephalic reticular formation (RFMes), which are believed to inhibit the neurons in the pons that generate paradoxical sleep (PS or REMS), are submitted to homeostatic regulation under conditions of sleep deprivation (SD) by enforced waking during the day in mice. Using immunofluorescence, we investigated first, by staining for c-Fos, whether GABAergic RFMes neurons are active during SD and then, by staining for receptors, whether their activity is associated with homeostatic changes in GABAA or acetylcholine muscarinic type 2 (AChM2) receptors (Rs), which evoke inhibition. We found that a significantly greater proportion of the GABAergic neurons were positively stained for c-Fos after SD (∼27%) as compared to sleep control (SC; ∼1%) and sleep recovery (SR; ∼6%), suggesting that they were more active during waking with SD and less active or inactive during sleep with SC and SR. The density of GABAARs and AChM2Rs on the plasma membrane of the GABAergic neurons was significantly increased after SD and restored to control levels after SR. We conclude that the density of these receptors is increased on RFMes GABAergic neurons during presumed enhanced activity with SD and is restored to control levels during presumed lesser or inactivity with SR. Such increases in GABAAR and AChM2R with sleep deficits would be associated with increased susceptibility of the wake-active GABAergic neurons to inhibition from GABAergic and cholinergic sleep-active neurons and to thus permitting the onset of sleep and PS with muscle atonia.

Recovery of consciousness and an injured ascending reticular activating system in a patient who survived cardiac arrest: A case report.

We report on a patient who survived cardiac arrest and showed recovery of consciousness and an injured ARAS at the early stage of hypoxic-ischemic brain injury (HI- BI) for 3 weeks, which was demonstrated by diffusion tensor tractography (DTT).A 52-year-old male patient who had suffered cardiac arrest caused by acute coronary syndrome was resuscitated immediately by a layman and paramedics for ∼25 minutes. He was then transferred immediately to the emergency room of a local medical center. When starting rehabilitation at 2 weeks after onset, his consciousness was impaired, with a Glasgow Coma Scale (GCS) score of 8 and Coma Recovery Scale-Revised (GRS-R) score of 8. He underwent comprehensive rehabilitative therapy, including drugs for recovery of consciousness. He recovered well and rapidly so that his consciousness had recovered to full scores in terms of GCS:15 and GRS-R:23 at 5 weeks after onset.The left lower dorsal and right lower ventral ARAS had become thicker on 5-week DTT compared with 2-week DTT (Fig. 1B). Regarding the change of neural connectivity of the thalamic ILN, increased neural connectivity to the basal forebrain and prefrontal cortex was observed in both hemispheres on 5-week DTT compared with 2-week DTT.Recovery of an injured ARAS was demonstrated in a patient who survived cardiac arrest and his consciousness showed rapid and good recovery for 3 weeks at the early stage of HI-BI.

Recovery From Vegetative State to Minimally Conscious State: A Case Report.

In this study, we attempted to demonstrate the change of the ascending reticular activating system (ARAS) concurrent with the recovery from a vegetative state (VS) to a minimally conscious state (MCS) in a patient with brain injury. A 54-year-old male patient had suffered from head trauma and underwent cardiopulmonary resuscitation immediately after head trauma. At 10 months after onset, the patient exhibited impaired consciousness, with a Coma Recovery Scale-Revised (CRS-R) score of 7 (auditory function: 1, visual function: 2, motor function: 1, verbal function: 1, communication: 0, and arousal: 2) and underwent the ventriculoperitoneal shunt operation for hydrocephalus. After the operation, he began comprehensive rehabilitative therapy. At post-op 2 and 8 weeks, his CRS-R score had recovered to 15 (3/3/4/1/1/3) and 17 (3/3/4/2/2/3), respectively. In terms of configuration on diffusion tensor tractography (DTT), there was no significant change in the lower portion of the ARAS. Regarding the change of neural connectivity of the thalamic intralaminar nucleus, increased neural connectivities to the hypothalamus, basal forebrain, prefrontal cortex, anterior cingulate cortex, and parietal cortex were observed in both hemispheres on post-op DTTs compared with pre-op DTT. We report on a patient with brain injury who showed change of the ARAS concurrent with the recovery from a VS and a MCS.

Recovery of Hypersomnia Concurrent With Recovery of an Injured Ascending Reticular Activating System in a Stroke Patient: A Case Report.

We report on a stroke patient who showed recovery of hypersomnia concurrent with the recovery of an injured ascending reticular activating system (ARAS), which was demonstrated by diffusion tensor tractography (DTT).A 70-year-old female patient underwent coiling of the left ruptured posterior communicating artery after subarachnoid hemorrhage and both extraventricular drainage for management of an intraventricular hemorrhage. At 2 months after onset, when she started rehabilitation, she exhibited intact consciousness, with the full score on the Glasgow Coma Scale: 15. However, she showed severe hypersomnia: she always fell asleep without external stimulation and the Epworth Sleepiness Scale (EPS) score was 24 (full score: 24, cut off for hypersomnia: 10). She underwent comprehensive rehabilitative therapy, including neurotropic drugs, physical therapy, and occupational therapy. Her hypersomnia has shown improvement as 14 (3 months after onset), 11 (4 months after onset), 7 (12 months after onset), and 6 (24 months after onset), respectively.On 2-month DTT, narrowing of both lower dorsal and ventral ARASs was observed on both sides: in particular, among 4 neural tracts of the lower ARAS, the right lower ventral ARAS was the narrowest. By contrast, on 24-month DTT, the 4 narrowed neural tracts of both lower dorsal and ventral ARASs were thickened compared with those of 2-month DTT.Recovery of hypersomnia with recovery of an injured lower ARAS on DTT was observed in a stroke patient. Our results suggest that evaluation of the lower ARAS using DTT might be useful for stroke patients with hypersomnia.

CORRELATION INDICES OF CEREBRAL HEMODYNAMICS AND ELECTRICAL ACTIVITY IN CHILDREN WITH IMPAIRED MOTOR SKILLS.

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 Ascending Reticular Activating System in a Patient With Severe Injury of the Cerebral Cortex: A Case Report.

We reported on the ascending reticular activating system (ARAS) finding of a patient in whom severe injury of the cerebral cortex was detected following a hypoxic-ischemic brain injury (HIBI).A 67-year-old female patient who suffered from HIBI induced by cardiac arrest after surgery for lumbar disc herniation underwent cardiopulmonary resuscitation approximately 20 to 30 minutes after cardiac arrest. The patient exhibited impaired alertness, with a Glasgow Coma Scale (GCS) score of 4 (eye opening: 2, best verbal response: 1, and best motor response: 1). Approximately 3 years after onset, she began to whimper sometimes and showed improved consciousness, with a GCS score of 10 (eye opening: 4, best verbal response: 2, and best motor response: 4) and Coma Recovery Scale-Revised score of 9 (auditory function: 1, visual function: 1, motor function: 2, verbal function: 2, communication: 1, and arousal: 2).Results of diffusion tensor tractography for the upper connectivity of the ARAS showed decreased neural connectivity to each cerebral cortex in both hemispheres. The right lower ARAS between the pontine reticular formation and the thalamic intralaminar nuclei (ILN) was thinner compared with the left side.Severe injury of the upper portion of the ARAS between the thalamic ILN and cerebral cortex was demonstrated in a patient with some level of consciousness.

Evidence for a role of the reticulospinal system in recovery of skilled reaching after cortical stroke: initial results from a model of ischemic cortical injury.

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.