Early rehabilitation model shows positive effects on neural degeneration and recovery from neuromotor deficits following traumatic brain injury

This study used an experimental early rehabilitation model combining an enriched environment, multisensory (visual, acoustic and olfactory) stimulation and motor training after traumatic brain injury (via fluid-percussion model) to simulate early multisensory rehabilitation. This therapy will be used by brain injured patients to improve neural plasticity and to restore brain integration functions. Motor dysfunction was evaluated using a composite neuroscore test. Direct structural effects of traumatic brain injury were examined using Fluoro-Jade staining, which allows identification of degenerating neural cell bodies and processes. Animals in the rehabilitation model group performed significantly better when tested for neuromotor function than the animals in standard housing in the 7-day and 15-day interval after injury (7d: p=0.005; 15d: p<0.05). Statistical analysis revealed significantly lower numbers of Fluoro-Jade positive cells (degenerating neurons) in the rehabilitation model group (n=5: mean 13.4) compared to the standard housing group (n=6: mean 123.8) (p<0.005). It appears that the housing of animals in the rehabilitation model led to a clear functional increase in neuromotor functions and to reduced neural loss compared with the animal group in standard housing.     

Action observation treatment: a novel tool in neurorehabilitation

This review focuses on a novel rehabilitation approach known as action observation treatment (AOT). It is now a well-accepted notion in neurophysiology that the observation of actions performed by others activates in the perceiver the same neural structures responsible for the actual execution of those same actions. Areas endowed with this action observation–action execution matching mechanism are defined as the mirror neuron system. AOT exploits this neurophysiological mechanism for the recovery of motor impairment. During one typical session, patients observe a daily action and afterwards execute it in context. So far, this approach has been successfully applied in the rehabilitation of upper limb motor functions in chronic stroke patients, in motor recovery of Parkinson''s disease patients, including those presenting with freezing of gait, and in children with cerebral palsy. Interestingly, this approach also improved lower limb motor functions in post-surgical orthopaedic patients. AOT is well grounded in basic neuroscience, thus representing a valid model of translational medicine in the field of neurorehabilitation. Moreover, the results concerning its effectiveness have been collected in randomized controlled studies, thus being an example of evidence-based clinical practice.     

早期康复治疗在重度颅脑损伤患者中应用的临床疗效观察

目的：观察早期康复治疗在重度颅脑损伤患者中应用的临床疗效,探讨提高重度颅脑损伤患者临床疗效的治疗方法。方法：选择重度颅脑损伤患者72例,根据康复治疗的时间不同,分为早期组与非早期组,比较两组患者康复治疗3个月后Fugl-Meyer评分、Barthel指数和神经功能恢复情况。结果：早期组患者的,临床疗效好于非早期组患者,两者在上述方面比较,差异均具有统计学意5k（P〈0．05）。结论：对于重度颅脑损伤患者,应积极施行早期康复治疗,可促进患者神经功能恢复,提高l临床疗效。     

早期康复锻炼对脑外伤患者肢体功能障碍的影响

目的：探讨早期康复锻炼对重型脑外伤患者肢体功能障碍的影响。方法：将62例脑外伤肢体功能障碍患者,随机分为康复护理组（31例）和对照组（31例）。对照组给予神经外科常规治疗和护理;在此基础上,康复护理组采用早期肢体康复锻炼。分别于入选治疗前和治疗后4周、12周进行测评。采用Fugl-meyer评分（FMA）评定运动功能;采用Barthel指数评定日常生活自理能力（ADL）。对比两组FMA和ADL指数。结果：两组患者的Barthel指数和Fugl-meyer评分均有一定程度的改善,康复护理组的改善幅度明显优于对照组（P〈0.01orP〈0.001）。结论：重型脑外伤患者接受早期综合康复护理能明显改善肢体运动功能,提高日常生活活动能力,提高患者的生存质量。     

Recovery of the motor function of the arm with the aid of a hand exoskeleton controlled by a brain–computer interface in a patient with an extensive brain lesion

The dynamics of motor function recovery in a patient with an extensive brain lesion has been investigated during a course of neurorehabilitation assisted by a hand exoskeleton controlled by a brain–computer interface. Biomechanical analysis of the movements of the paretic arm recorded during the rehabilitation course was used for an unbiased assessment of motor function. Fifteen procedures involving hand exoskeleton control (one procedure per week) yielded the following results: (a) the velocity profile for targeted movements of the paretic hand became nearly bell-shaped; (b) the patient began to extend and abduct the hand, which was flexed and adducted at the beginning of the course; and (c) the patient started supinating the forearm, which was pronated at the beginning of the rehabilitation course. The first result is interpreted as improvement of the general level of control over the paretic hand, and the two other results are interpreted as a decrease in spasticity of the paretic hand.     

Enhancing Sensorimotor Activity by Controlling Virtual Objects with Gaze

This fMRI work studies brain activity of healthy volunteers who manipulated a virtual object in the context of a digital game by applying two different control methods: using their right hand or using their gaze. The results show extended activations in sensorimotor areas, not only when participants played in the traditional way (using their hand) but also when they used their gaze to control the virtual object. Furthermore, with the exception of the primary motor cortex, regional motor activity was similar regardless of what the effector was: the arm or the eye. These results have a potential application in the field of the neurorehabilitation as a new approach to generate activation of the sensorimotor system to support the recovery of the motor functions.     

Motor Enrichment and the Induction of Plasticity Before or After Brain Injury

Voluntary exercise, treadmill activity, skills training, and forced limb use have been utilized in animal studies to promote brain plasticity and functional change. Motor enrichment may prime the brain to respond more adaptively to injury, in part by upregulating trophic factors such as GDNF, FGF-2, or BDNF. Discontinuation of exercise in advance of brain injury may cause levels of trophic factor expression to plummet below baseline, which may leave the brain more vulnerable to degeneration. Underfeeding and motor enrichment induce remarkably similar molecular and cellular changes that could underlie their beneficial effects in the aged or injured brain. Exercise begun before focal ischemic injury increases BDNF and other defenses against cell death and can maintain or expand motor representations defined by cortical microstimulation. Interfering with BDNF synthesis causes the motor representations to recede or disappear. Injury to the brain, even in sedentary rats, causes a small, gradual increase in astrocytic expression of neurotrophic factors in both local and remote brain regions. The neurotrophic factors may inoculate those areas against further damage and enable brain repair and use-dependent synaptogenesis associated with recovery of function or compensatory motor learning. Plasticity mechanisms are particularly active during time-windows early after focal cortical damage or exposure to dopamine neurotoxins. Motor and cognitive impairments may contribute to self-imposed behavioral impoverishment, leading to a reduced plasticity. For slow degenerative models, early forced forelimb use or exercise has been shown to halt cell loss, whereas delayed rehabilitation training is ineffective and disuse is prodegenerative. However, it is possible that, in the chronic stages after brain injury, a regimen of exercise would reactivate mechanisms of plasticity and thus enhance rehabilitation targeting residual functional deficits.     

节律性听觉刺激下的神经振荡同步化及其应用

大脑的感觉、情绪、认知等功能与其神经振荡模式有密切的联系。通过施加节律性刺激可以调控大脑的神经振荡模式,进而影响个体感受、情绪状态和认知功能等。与近年来常见的非侵入性电刺激和磁刺激相比,同样依赖于外部刺激输入的节律性感觉刺激具有成本低、易操作等优点,被认为是一种极具潜力的神经调控手段。本文以节律性听觉刺激为例,系统综述了不同类型的节律性听觉刺激如何影响大脑的神经振荡模式,进而影响相关状态和功能;并通过总结外部节律性听觉刺激对个体感知觉、情绪与认知功能的影响,讨论其生理机制和应用前景。     

Soy isoflavones and cognitive function

There is growing interest in the physiological functions of soy isoflavones, especially in whether they affect cognitive function and have beneficial effects on neurodegenerative diseases. Here we review the recent evidence from clinical and experimental studies supporting a role for soy isoflavones in cognitive function. Soy isoflavones may mimic the actions and functions of estrogens on brain, and they have been shown to have positive effects on the cognitive function in females; however, studies on their effects on spatial memory have not provided consistent results in males. Although data from humans, cultures, and animal models are currently insufficient for elucidating the metabolism of soy isoflavone actions on cognitive function and the nervous system, we suggest two putative pathways; (1) an estrogen receptor-mediated pathway and (2) via the inhibition of tyrosine kinase, in particular by genistein, which is one of the soy isoflavones. Although soy isoflavones appear to have a positive effect on brain function, further research is needed to determine not only the efficacy but also the safety of soy isoflavones on the nervous system and cognitive function.     

Neurophysiological and Neuropsychological Indicators of the Efficiency of the Rehabilitation of Patients with Parkinsonism

This work experimentally showed the possibility of using neurophysiological and neuropsychological indicators of the efficiency of rehabilitation to better understand brain mechanisms of the syndrome and the compensation of deficiencies using a model of rehabilitation of motor and cognitive functions in patients with Parkinson's disease. A study paradigm was developed in three patients with a predominantly akinetic–rigid form of parkinsonism. The methods of the study included clinical neurological, neuropsychological, neurophysiological, and psychometric analyses. A positive correlation was found between clinical, psychometric, and neuropsychological measures, and a positive correlation between neurophysiological and neuropsychological measures was found only in the subject with the minimum dysfunction in this group, with the shortest period of illness, and predominantly right-hemispheric lateralization of the processes.     

Rehabilitation potential of post-stroke patients training for kinesthetic movement imagination: Motor and cognitive aspects

The rehabilitation potential of post-stroke patients was evaluated after a rehabilitation procedure using a hand exoskeleton controlled via a brain–computer interface (BCI). Examples are given for parameters describing the motor and cognitive functions and the capacity for kinesthetic movement imagination. It is emphasized that instrumental quantitative methods are important to use for adequate assessment of both the rehabilitation potential and the effectiveness of the BCI + exoskeleton procedure.     

Neuroplasticity. Key to recovery after central nervous system injury.

After an injury to the central nervous system, physical and cognitive impairments and disabilities often abate. These gains may be partly mediated by mechanisms that allow reorganizing of the structure and function within gray and white matter. The potential to enhance neurologic recovery by manipulating the brain and spinal cord must now be considered in clinical practice. Today''s rehabilitation routines may not encourage maximum recovery. Indeed, some commonly used physical and pharmacologic methods could inhibit the restoration of motor activities such as walking. On the other hand, therapies that use our expanding knowledge of neuroplasticity could lead to better results for patients.     

An ameliorative effect of recovery sleep on total sleep deprivation-induced neurodegeneration

Neurodegenerative changes following sleep deprivation (SD) result in debilitating behavioral and cognitive dysfunction. SD causes gradual cognitive impairment and later results in neurodegeneration. These changes are thought to be the consequences of cellular disorganization and degeneration in selected brain areas – the hippocampus, prefrontal cortex, amygdala, and hypothalamus. We investigated the histological changes in mice exposed to 6 days SD and to the effects of 2 days of recovery sleep in the brain regions listed above. Cytological changes, total viable cell count in hippocampal subregions, Bcl-2 expression, and degenerative changes like cell morphology and membrane integrity of neurons were evaluated. Results demonstrated that prolonged SD decreased the count of viable and healthy cells and caused a decrease in Bcl-2 positive cells and an increase in degenerated cells with pyknotic morphology, chromatolysis and darkly stained cytoplasm. Degenerative changes were ameliorated by 2 days of recovery sleep or rehabilitation after SD. Data suggest that chronic SD constitutes a severe threat to the brain and leads to neurodegeneration, while rehabilitation or recovery sleep ameliorates or protects the brain from neurodegenerative challenges.     

Association of childhood trauma with cognitive function in healthy adults: a pilot study

Background  

Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults.     

Walking but not barking improves verb recovery: implications for action observation treatment in aphasia rehabilitation

Recent studies have shown that action observation treatment without concomitant verbal cue has a positive impact on the recovery of verb retrieval deficits in aphasic patients. In agreement with an embodied cognition viewpoint, a hypothesis has been advanced that gestures and language form a single communication system and words whose retrieval is facilitated by gestures are semantically represented through sensory-motor features. However, it is still an open question as to what extent this treatment approach works. Results from the recovery of motor deficits have suggested that action observation promotes motor recovery only for actions that are part of the motor repertoire of the observer. The aim of the present experiment was to further investigate the role of action observation treatment in verb recovery. In particular, we contrasted the effects induced by observing human actions (e.g. dancing, kicking, pointing, eating) versus non human actions (e.g. barking, printing). Seven chronic aphasic patients with a selective deficit in verb retrieval underwent an intensive rehabilitation training that included five daily sessions over two consecutive weeks. Each subject was asked to carefully observe 115 video-clips of actions, one at a time and, after observing them, they had to produce the corresponding verb. Two groups of actions were randomly presented: humans versus nonhuman actions. In all patients, significant improvement in verb retrieval was found only by observing video-clips of human actions. Moreover, follow-up testing revealed long-term verb recovery that was still present two months after the two treatments had ended. In support of the multimodal concept representation's proposal, we suggest that just the observation of actions pertaining to the human motor repertoire is an effective rehabilitation approach for verb recovery.     

The inhibition of mammalian target of rapamycin (mTOR) in improving inflammatory response after traumatic brain injury

Traumatic brain injury (TBI) provokes primary and secondary damage on endothelium and brain parenchyma, leading neurons die rapidly by necrosis. The mammalian target of rapamycin signalling pathway (mTOR) manages numerous aspects of cellular growth, and it is up-regulated after moderate to severe traumatic brain injury (TBI). Currently, the significance of this increased signalling event for the recovery of brain function is unclear; therefore, we used two different selective inhibitors of mTOR activity to discover the functional role of mTOR inhibition in a mouse model of TBI performed by a controlled cortical impact injury (CCI). Treatment with KU0063794, a dual mTORC1 and mTORC2 inhibitor, and with rapamycin as well-known inhibitor of mTOR, was performed 1 and 4 hours subsequent to TBI. Results proved that mTOR inhibitors, especially KU0063794, significantly improved cognitive and motor recovery after TBI, reducing lesion volumes. Also, treatment with mTOR inhibitors ameliorated the neuroinflammation associated with TBI, showing a diminished neuronal death and astrogliosis after trauma. Our findings propose that the involvement of selective mTORC1/2 inhibitor may represent a therapeutic strategy to improve recovery after brain trauma.     

Evidence for training-induced plasticity in multisensory brain structures: an MEG study

Multisensory learning and resulting neural brain plasticity have recently become a topic of renewed interest in human cognitive neuroscience. Music notation reading is an ideal stimulus to study multisensory learning, as it allows studying the integration of visual, auditory and sensorimotor information processing. The present study aimed at answering whether multisensory learning alters uni-sensory structures, interconnections of uni-sensory structures or specific multisensory areas. In a short-term piano training procedure musically naive subjects were trained to play tone sequences from visually presented patterns in a music notation-like system [Auditory-Visual-Somatosensory group (AVS)], while another group received audio-visual training only that involved viewing the patterns and attentively listening to the recordings of the AVS training sessions [Auditory-Visual group (AV)]. Training-related changes in cortical networks were assessed by pre- and post-training magnetoencephalographic (MEG) recordings of an auditory, a visual and an integrated audio-visual mismatch negativity (MMN). The two groups (AVS and AV) were differently affected by the training. The results suggest that multisensory training alters the function of multisensory structures, and not the uni-sensory ones along with their interconnections, and thus provide an answer to an important question presented by cognitive models of multisensory training.     

Observation and execution of upper-limb movements as a tool for rehabilitation of motor deficits in paretic stroke patients: protocol of a randomized clinical trial

ABSTRACT: BACKGROUND: Evidence exist that motor observation activates the same cortical motor areas that are involved in the performance of the observed actions. The so called "mirror neuron system" has been proposed to be responsible for this phenomenon. We employ this neural system and its capability to re-enact stored motor representations as a tool for rehabilitating motor control. In our new neurorehabilitative schema (videotherapy) we combine observation of daily actions with concomitant physical training of the observed actions focusing on the upper limbs. Following a pilot study in chronic patients in an ambulatory setting, we currently designed a new multicenter clinical study dedicated to patients in the sub-acute state after stroke using a home-based self-induced training. Within our protocol we assess 1) the capability of action observation to elicit rehabilitational effects in the motor system, and 2) the capacity of this schema to be performed by patients without assistance from a physiotherapist. The results of this study would be of high health and economical relevance. Methods/ Design A controlled, randomized, multicenter, paralleled, 6 month follow-up study will be conducted on three groups of patients: one group will be given the experimental treatment whereas the other two will participate in a control treatment. All patients will undergo their usual rehabilitative treatment beside participation in the study. The experimental condition consists in the observation and immediate imitation of common daily hand and arm actions. The two parallel control groups are a placebo group and a group receiving usual rehabilitation without any trial-related treatment. Trial randomization is provided via external data management. The primary efficacy endpoint is the improvement of the experimental group in a standardized motor function test (Wolf Motor Function Test) relative to control groups. Further assessments refer to subjective and qualitative rehabilitational scores. This study has been reviewed and approved by the ethics committee of Aachen University. DISCUSSION: This therapy provides an extension of therapeutic procedures for recovery after stroke and emphasizes the importance of action perception in neurorehabilitation The results of the study could become implemented into the wide physiotherapeutic practice, for example as an ad on and individualized therapy.     

Effects of low-frequency repetitive transcranial magnetic stimulation on upper extremity motor recovery and functional outcomes in chronic stroke patients: A randomized controlled trial

Background: Repetitive transcranial magnetic stimulation (rTMS) was suggested as a preconditioning method that would increase brain plasticity and that it would be optimal to combine rTMS with intensive rehabilitation.

Objective: To assess the efficacy of inhibitory rTMS on upper extremity motor recovery and functional outcomes in chronic ischemic stroke patients.

Methods: In this randomized controlled trial, experimental group received low-frequency (LF) rTMS to the primary motor cortex of the unaffected side?+?physical therapy (PT), and control group received PT.

Results: No statistically significant difference was found in baseline demographical and clinical characteristics of the subjects including stroke severity or severity of paralysis prior to intervention. There were statistically significant improvements in all clinical outcome measures except for the Brunnstrom Recovery Stages. Fugl–Meyer Assessment, Box and Block test, motor and total scores of Functional Independence Measurement (FIM), and Functional Ambulation Scale (FAS) scores were significantly increased in both groups, however, these changes were significantly greater in the rTMS group except for FAS score. FIM cognitive scores and standardized mini-mental test scores were significantly increased and distal and hand Modified Ashworth Scale scores were significantly decreased only in the rTMS group (p?Conclusions: LF-rTMS can safely facilitate upper extremity motor recovery in patients with chronic ischemic stroke. TMS seems to be a promising treatment for motor, functional, and cognitive deficits in chronic stroke. Further studies with a larger number of patients with longer follow-up periods are needed to establish its effectiveness in stroke rehabilitation.