Archive for category Neuroplasticity

[ARTICLE] Efficacy and Brain Imaging Correlates of an Immersive Motor Imagery BCI-Driven VR System for Upper Limb Motor Rehabilitation: A Clinical Case Report – Full Text

To maximize brain plasticity after stroke, a plethora of rehabilitation strategies have been explored. These include the use of intensive motor training, motor-imagery (MI), and action-observation (AO). Growing evidence of the positive impact of virtual reality (VR) techniques on recovery following stroke has been shown. However, most VR tools are designed to exploit active movement, and hence patients with low level of motor control cannot fully benefit from them. Consequently, the idea of directly training the central nervous system has been promoted by utilizing MI with electroencephalography (EEG)-based brain-computer interfaces (BCIs). To date, detailed information on which VR strategies lead to successful functional recovery is still largely missing and very little is known on how to optimally integrate EEG-based BCIs and VR paradigms for stroke rehabilitation. The purpose of this study was to examine the efficacy of an EEG-based BCI-VR system using a MI paradigm for post-stroke upper limb rehabilitation on functional assessments, and related changes in MI ability and brain imaging. To achieve this, a 60 years old male chronic stroke patient was recruited. The patient underwent a 3-week intervention in a clinical environment, resulting in 10 BCI-VR training sessions. The patient was assessed before and after intervention, as well as on a one-month follow-up, in terms of clinical scales and brain imaging using functional MRI (fMRI). Consistent with prior research, we found important improvements in upper extremity scores (Fugl-Meyer) and identified increases in brain activation measured by fMRI that suggest neuroplastic changes in brain motor networks. This study expands on the current body of evidence, as more data are needed on the effect of this type of interventions not only on functional improvement but also on the effect of the intervention on plasticity through brain imaging.

Introduction

Worldwide, stroke is a leading cause of adult long-term disability (Mozaffarian et al., 2015). From those who survive, an increased number is suffering with severe cognitive and motor impairments, resulting in loss of independence in their daily life such as self-care tasks and participation in social activities (Miller et al., 2010). Rehabilitation following stroke is a multidisciplinary approach to disability which focuses on recovery of independence. There is increasing evidence that chronic stoke patients maintain brain plasticity, meaning that there is still potential for additional recovery (Page et al., 2004). Traditional motor rehabilitation is applied through physical therapy and/or occupational therapy. Current approaches of motor rehabilitation include functional training, strengthening exercises, and range of movement exercises. In addition, techniques based on postural control, stages of motor learning, and movement patterns have been proposed such as in the Bobath concept and Bunnstrom approach (amongst others) (Bobath, 1990). After patients complete subacute rehabilitation programs, many still show significant upper limb motor impairment. This has important functional implications that ultimately reduce their quality of life. Therefore, alternative methods to maximize brain plasticity after stroke need to be developed.

So far, there is growing evidence that action observation (AO) (Celnik et al., 2008) and motor imagery (MI) improve motor function (Mizuguchi and Kanosue, 2017) but techniques based on this paradigm are not widespread in clinical settings. As motor recovery is a learning process, the potential of MI as a training paradigm relies on the availability of an efficient feedback system. To date, a number of studies have demonstrated the positive impact of virtual-reality (VR) based on neuroscientific grounds on recovery, with proven effectiveness in the stroke population (Bermúdez i Badia et al., 2016). However, patients with no active movement cannot benefit from current VR tools due to low range of motion, pain, fatigue, etc. (Trompetto et al., 2014). Consequently, the idea of directly training the central nervous system was promoted by establishing an alternative pathway between the user’s brain and a computer system.

This is possible by using electroencephalography (EEG)-based Brain-Computer Interfaces (BCIs), since they can provide an alternative non-muscular channel for communication and control to the external world (Wolpaw et al., 2002), while they could also provide a cost-effective solution for training (Vourvopoulos and Bermúdez, 2016b). In rehabilitation, BCIs could offer a unique tool for rehabilitation since they can stimulate neural networks through the activation of mirror neurons (Rizzolatti and Craighero, 2004) by means of action-observation (Kim et al., 2016), motor-intent and motor-imagery (Neuper et al., 2009), that could potentially lead to post-stroke motor recovery. Thus, BCIs could provide a backdoor to the activation of motor neural circuits that are not stimulated through traditional rehabilitation techniques.

In EEG-based BCI systems for motor rehabilitation, Alpha (8–12 Hz) and Beta (12–30 Hz) EEG rhythms are utilized since they are related to motor planning and execution (McFarland et al., 2000). During a motor attempt or motor imagery, the temporal pattern of the Alpha rhythms desynchronizes. This rhythm is also named Rolandic Mu-rhythm or the sensorimotor rhythm (SMR) because of its localization over the sensorimotor cortices. Mu-rhythms are considered indirect indications of functioning of the mirror neuron system and general sensorimotor activity (Kropotov, 2016). These are often detected together with Beta rhythm changes in the form of an event-related desynchronization (ERD) when a motor action is executed (Pfurtscheller and Lopes da Silva, 1999). These EEG patterns are primarily detected during task-based EEG (e.g., when the participant is actively moving or imagining movement) and they are of high importance in MI-BCIs for motor rehabilitation.

A meta-analysis of nine studies (combined N = 235, sample size variation 14 to 47) evaluated the clinical effectiveness of BCI-based rehabilitation of patients with post-stroke hemiparesis/hemiplegia and concluded that BCI technology could be effective compared to conventional treatment (Cervera et al., 2018). This included ischemic and hemorrhagic stroke in both subacute and chronic stages of stoke, between 2 to 8 weeks. Moreover, there is evidence that BCI-based rehabilitation promotes long-lasting improvements in motor function of chronic stroke patients with severe paresis (Ramos-Murguialday et al., 2019), while overall BCI’s are starting to prove their efficacy as rehabilitative technologies in patients with severe motor impairments (Chaudhary et al., 2016).

The feedback modalities used for BCI motor rehabilitation include: non-embodied simple two-dimensional tariffs on a screen (Prasad et al., 2010Mihara et al., 2013), embodied avatar representation of the patient on a screen or with augmented reality (Holper et al., 2010Pichiorri et al., 2015), neuromuscular electrical stimulation (NMES) (Kim et al., 2016Biasiucci et al., 2018). and robotic exoskeletal orthotic movement facilitation (Ramos-Murguialday et al., 2013Várkuti et al., 2013Ang et al., 2015). In addition, it has been shown that multimodal feedback lead to a significantly better performance in motor-imagery (Sollfrank et al., 2016) but also multimodal feedback combined with motor-priming, (Vourvopoulos and Bermúdez, 2016a). However, there is no evidence which modalities are more efficient in stroke rehabilitation are.

Taking into account all previous findings in the effects of multimodal feedback in MI training, the purpose of this case study is to examine the effect of the MI paradigm as a treatment for post-stroke upper limb motor dysfunction using the NeuRow BCI-VR system. This is achieved through the acquisition of clinical scales, dynamics of EEG during the BCI treatment, and brain activation as measured by functional MRI (fMRI). NeuRow is an immersive VR environment for MI-BCI training that uses an embodied avatar representation of the patient arms and haptic feedback. The combination of MI-BCIs with VR can reinforce activation of motor brain areas, by promoting the illusion of physical movement and the sense of embodiment in VR (Slater, 2017), and hence further engaging specific neural networks and mobilizing the desired neuroplastic changes. Virtual representation of body parts paves the way to include action observation during treatment. Moreover, haptic feedback is added since a combination of feedback modalities could prove to be more effective in terms of motor-learning (Sigrist et al., 2013). Therefore, the target of this system is to be used by patients with low or no levels of motor control. With this integrated BCI-VR approach, severe cases of stroke survivors may be admitted to a VR rehabilitation program, complementing traditional treatment.

Methodology

Patient Profile

In this pilot study we recruited a 60 years old male patient with left hemiparesis following cerebral infarct in the right temporoparietal region 10 months before. The participant had corrected vision through eyewear, he had 4 years of schooling and his experience with computers was reported as low. Moreover, the patient was on a low dose of diazepam (5 mg at night to help sleep), dual antiplatelet therapy, anti-hypertensive drug and metformin. Hemiparesis was associated with reduced dexterity and fine motor function; however, sensitivity was not affected. Other sequelae of the stroke included hemiparetic gait and dysarthria. Moreover, a mild cognitive impairment was identified which did not interfere with his ability to perform the BCI-VR training. The patient had no other relevant comorbidities. Finally, the patient was undergoing physiotherapy and occupational therapy at the time of recruitment and had been treated with botulinum toxin infiltration 2 months before due to focal spasticity of the biceps brachii.

Intervention Protocol

The patient underwent a 3-weeks intervention with NeuRow, resulting in 10 BCI sessions of a 15 min of exposure in VR training per session. Clinical scales, motor imagery capability assessment, and functional -together with structural- MRI data had been gathered in three time-periods: (1) before (serving as baseline), (2) shortly after the intervention and (3) one-month after the intervention (to assess the presence of long-term changes). Finally, electroencephalographic (EEG) data had been gathered during all sessions, resulting in more than 20 datasets of brain electrical activity.

The experimental protocol was designed in collaboration with the local healthcare system of Madeira, Portugal (SESARAM) and approved by the scientific and ethic committees of the Central Hospital of Funchal. Finally, written informed consent was obtained from the participant upon recruitment for participating to the study but also for the publication of the case report in accordance with the 1964 Declaration of Helsinki.

Assessment Tools

A set of clinical scales were acquired including the following:

1. Montreal Cognitive Assessment (MoCA). MoCA is a cognitive screening tool, with a score range between 0 and 30 (a score greater than 26 is considered to be normal) validated also for the Portuguese population, (Nasreddine et al., 2005).

2. Modified Ashworth scale (MAS). MAS is a 6-point rating scale for measuring spasticity. The score range is 0, 1, 1+, 2, 3, and 4 (Ansari et al., 2008).

3. Fugl-Meyer Assessment (FMA). FMA is a stroke specific scale that assesses motor function, sensation, balance, joint range of motion and joint pain. The motor domain for the upper limb has a maximum score of 66 (Fugl-Meyer et al., 1975).

4. Stroke Impact Scale (SIS). SIS is a subjective scale of the perceived stroke impact and recovery as reported by the patient, validated for the Portuguese population. The score of each domain of the questionnaire ranges from 0 to 100 (Duncan et al., 1999).

5. Vividness of Movement Imagery Questionnaire (VMIQ2). VMIQ2 is an instrument that assess the capability of the participant to perform imagined movements from external perspective (EVI), internal perspective imagined movements (IVI) and finally, kinesthetic imagery (KI) (Roberts et al., 2008).

NeuRow BCI-VR System

EEG Acquisition

For EEG data acquisition, the Enobio 8 (Neuroelectrics, Barcelona, Spain) system was used. Enobio is a wearable wireless EEG sensor with 8 EEG channels for the recording and visualization of 24-bit EEG data at 500 Hz and a triaxial accelerometer. The spatial distribution of the electrodes followed the 10–20 system configuration (Klem et al., 1999) with the following electrodes over the somatosensory and motor areas: Frontal-Central (FC5, FC6), Central (C1, C2, C3, C4), and Central-Parietal (CP5, CP6) (Figure 1A). The EEG system was connected via Bluetooth to a dedicated desktop computer, responsible for the EEG signal processing and classification, streaming the data via UDP through the Reh@Panel (RehabNet Control Panel) for controlling the virtual environment. The Reh@Panel is a free tool that acts as a middleware between multiple interfaces and virtual environments (Vourvopoulos et al., 2013).

FIGURE 1

Figure 1. Experimental setup, including: (A) the wireless EEG system; (B) the Oculus HMD, together with headphones reproducing the ambient sound from the virtual environment; (C) the vibrotactile modules supported by a custom-made table-tray, similar to the wheelchair trays used for support; (D) the visual feedback with NeuRow game. A written informed consent was obtained for the publication of this image.

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[ARTICLE] Increased Sensorimotor Cortex Activation With Decreased Motor Performance During Functional Upper Extremity Tasks Poststroke – Full Text

Abstract

Background and Purpose: Current literature has focused on identifying neuroplastic changes associated with stroke through tasks and in positions that are not representative of functional rehabilitation. Emerging technologies such as functional near-infrared spectroscopy (fNIRS) provide new methods of expanding the area of neuroplasticity within rehabilitation. This study determined the differences in sensorimotor cortex activation during unrestrained reaching and gripping after stroke.

Methods: Eleven individuals with chronic stroke and 11 neurologically healthy individuals completed reaching and gripping tasks under 3 conditions using their (1) stronger, (2) weaker, and (3) both arms together. Performance and sensorimotor cortex activation using fNIRS were collected. Group and arm differences were calculated using mixed analysis of covariance (covariate: age). Pairwise comparisons were used for post hoc analyses. Partial Pearson correlations between performance and activation were assessed for each task, group, and hemisphere.

Results: Larger sensorimotor activations in the ipsilesional hemisphere were found for the stroke compared with healthy group for reaching and gripping conditions despite poorer performance. Significant correlations were observed between gripping performance (with the weaker arm and both arms simultaneously) and sensorimotor activation for the stroke group only.

Discussion and Conclusions: Stroke leads to significantly larger sensorimotor activation during functional reaching and gripping despite poorer performance. This may indicate an increased sense of effort, decreased efficiency, or increased difficulty after stroke. fNIRS can be used for assessing differences in brain activation during movements in functional positions after stroke. This can be a promising tool for investigating possible neuroplastic changes associated with functional rehabilitation interventions in the stroke population.

Video Abstract available for more insights from the authors (see Video Abstract, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A269).

 

INTRODUCTION

Stroke is the leading cause of long-term disability in Canada, with approximately 405 000 Canadians currently living with its long-lasting effects.1 While the site of injury and the specific presentation of symptoms are heterogeneous, up to 70% of these individuals experience upper extremity hemiparesis,2 and even after rehabilitation, greater than 65% of this population have difficulty utilizing their affected limb in activities of daily living.3 Decreased use of the paretic arm can lead to chronic pain and weakness, decreased bone density,4 cerebral cortex changes,5and an overall decrease in quality of life.6 In addition, stroke rehabilitation and continual care are costly for the health care system.7 Therefore, it is important to maximize patient recovery in an effective and efficient manner.

One area that has been highly debated for rehabilitation efficacy is the side of arm training. Numerous reviews have stated conflicting and inconclusive results pertaining to benefits of the paretic (affected) arm or bilateral arm training8–10 and a few studies have recently investigated the effects of the nonparetic (less-affected) arm training.11,12 Investigating how stroke itself affects neural activation during unilateral and bilateral upper extremity activities may help explain the mechanisms underlying such training.

In individuals living with the chronic effects of stroke, nonnormal brain activation is commonly seen with irregular activation in both the ipsi- and contralesional hemispheres during movement. A meta-analysis of 20 studies13 calculated increases in contralesional primary motor cortex, and bilateral premotor and supplementary motor areas with use of the paretic hand compared with healthy individuals. Systematically reviewing 22 functional magnetic resonance imaging (fMRI) and positron emission tomography studies, Buma et al14 reported general initial increases in contra-, ipsi-, and perilesional activation during paretic upper extremity movement in individuals with cortical and subcortical strokes when compared with healthy adults. In addition, as paretic arm performance increased with training, these authors also showed that in many, but not all participants, activation decreased in areas such as the contralesional motor cortex (ie, ipsilateral to the movement arm), which is not typically activated in healthy individuals. Previous reviews have also reported increases in cortical activation of motor supporting areas (bilateral premotor and supplementary motor areas) later in recovery that are associated with greater function,15 although the opposite has also been reported.16

The majority of previously mentioned evidence utilized neuroimaging techniques that require an individual to remain fairly still, especially at the head, and recorded in the supine position. While there are many advantages to these techniques, such as high spatial resolution and penetration depth using fMRI, the functional imaging data acquired from these studies may not be truly indicative of the neural correlates involved during rehabilitation tasks. Thus, assessment of brain activation during upright, unrestrained, functional tasks is needed. Functional near-infrared spectroscopy (fNIRS) is an emerging neuroimaging device that has the capabilities of determining cortical activation while the participant is mobile. Similar to fMRI, fNIRS is an indirect measure of cortical activation that utilizes the neurovascular coupling theory to estimate changes in brain activity.17 Near-infrared light emitted by this device is absorbed by areas high in oxyhemoglobin or deoxyhemoglobin content and is measured through detectors placed on the individual’s head. When an increase in brain activity occurs, a typical overall increase in oxyhemoglobin concentration and a slight decrease in deoxyhemoglobin are observed.17 Due to its portability, fNIRS has been used to investigate cortical activation during various mobile tasks after stroke.18,19 To our knowledge, no work has been done to compare sensorimotor cortex activation of paretic, nonparetic, and bilateral arm movements poststroke using fNIRS.

Therefore, the primary purpose of this study was to investigate differences in cortical brain activation during performance of upper extremity activities in an upright position after stroke and in neurologically healthy individuals. Based on the current evidence, we hypothesized that greater sensorimotor cortex activation would be observed in the stroke group compared with the neurologically healthy group, particularly when using the weaker arm. For our secondary measures, we hypothesize that (1) individuals in the stroke group will perform worse than the control group when using their weaker arm and (2) cortical activation in the contralateral hemisphere (eg, ipsilesional hemisphere during paretic arm movements) will positively correlate with task performance.[…]

Continue —->  Increased Sensorimotor Cortex Activation With Decreased Moto… : Journal of Neurologic Physical Therapy

Figure 1
(A) Schematic of the environmental setup for the reaching task. Two adjacent Box and Block sets were placed in front of the participant. The left box was for the left hand and the right box was for the right hand. Arrows indicate the movement of the blocks from the box closest to the participant to the box further in front of the participant. (B) Schematic of the optode placements with reference to the international 10/10 system. Source probes are indicated by black circles and detector probes are indicated by gray circles.
Source
Increased Sensorimotor Cortex Activation With Decreased Motor Performance During Functional Upper Extremity Tasks Poststroke
Journal of Neurologic Physical Therapy43(3):141-150, July 2019.

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[Conference Paper] Modelling of a wearable jacket with sensors and actuators for upper limb rehabilitation

Abstract

Introduction Spinal Cord Injury (SCI) affects a large number of young people and, if left  untreated, can deal irreversible damage to the human body. Several studies have demonstrated the positive impact of physical therapy to the rehabilitation process, promoting neuro-plasticity and thus at least partial restoration of functionality of the body and gait. These studies focus on the implementation of engineered solutions, such as robotic exoskeletons and virtual reality training regimens. The common denominator in most of them is the implementation of some form of Human-Machine Interface (HMI), for the control of these modalities by direct user feedback. These HMIs are based on a plethora of sensor arrays, ranging from direct motion-specific body data, such as Electroencephalography (EEG) and Electromyography (EMG) to more common sensor devices, such as accelerometers and gyroscopes. These sensors can provide direct measurements, tailored to the application at hand and provide the necessary data for the desired functionality. Materials and Methods The proposed device will function as a sensor array for the upper-body, providing live data for muscle activity, through the use of Electromyography (EMG) electrodes, as well as relative joint positioning and rotation, utilizing Inertial Measurement Units (IMUs), for the purpose of monitoring and Augmented Reality (AR) integration. Said motion data will be then used to enhance the users desired movement, through the use of Functional Electronic Stimulation (FES), by providing the necessary impulse to each muscle group, from the measured feedback. The relationship between sensor input and stimulation will allow for reinforcement of the users’ movements, promoting neuroplasticity and ease of movement in the process of neuro-rehabilitation. Furthermore, this modality will act as a platform for several other physiological measurements, such as heart rate and perspiration, essentially creating a functional Body-Area Network (BAN) of sensors. Integration with external motion actuators will be investigated, as a means to provide upper-body support, providing the necessary strength, as a means of easing the rehabilitation process and removing unnecessary stress from the user. Finally, interactions with implanted medical devices will be explored. Such devices could provide telemetry data from inside the body, to be used as a form of direct feedback for the designed Body Area Network (BAN), and the aforementioned stimulation and actuation.

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[BLOG POST] Sleep Evaluation and Treatment Support Patient Outcome

(Note:  In this guest blog from Grace Griesbach, Ph.D., and CNS’ National Director of Clinical Research, she explains that proper sleep is a vital component in the rehabilitation of brain injury).

Historically, quotes referring to sleep have been associated with well-being. This is not without substance. The importance of sleep is appreciated when one considers that it is observed across the vast majority of animal species. In humans and other higher mammals, lack of sleep has been demonstrated to impact physical, cognitive and emotional functions negatively. Physical consequences of sleep deprivation include compromised immune responses, as well as hormonal and metabolic alterations that in turn will impact overall health. Sleep also promotes emotional and psychological well-being. As for cognitive functions, sleep has been shown to facilitate learning and memory.

Moreover, animal studies have shown that neural plasticity changes allow for better memory to occur during sleep. Sleep driven neural plasticity is also evident during brain development and during times when healing is necessary. Given the multiple functions of sleep, it is evident that sleep-related problems should not be ignored.

Unfortunately, the prevalence of sleep disorders following brain injury is notably higher compared to the general population. Many of those that have endured a traumatic brain injury or stroke have difficulty initiating or maintaining sleep. Daytime sleepiness (hypersomnia) and fatigue are frequently reported complaints that are associated with insomnia. Apnea, a common breathing-related sleep disorder, is frequently observed during the chronic brain injury period. Apnea is defined as breathing cessation for fixed periods during sleep and contributes to arousals throughout the night; promoting fragmented sleep.

Sleep follows a particular overnight pattern consisting of repeated sleep cycles. Each cycle is comprised of one rapid eye movement (REM) stage and three non-REM stages. These stages are defined by different brain activity patterns that have been associated with particular physiological and neural plasticity processes.

Studies focused on proper sleep closely examine brain wave activity and body physiology throughout the various sleep stages. Some stages are particularly important for memory, emotional well-being, and cognitive function, and may be compromised by interrupted sleep. The golden standard of evaluating sleep is with an overnight polysomnography study performed by a certified sleep technologist. The technologist places electrodes on the scalp of the patient to record brain activity. Breathing, heart rate, oxygen levels, and limb movement are also recorded during sleep. Results from these recordings are sent to a board-certified sleep medicine physician, who creates a report on the diagnosis and a treatment plan.

Centre for Neuro Skills (CNS) offers a comprehensive multidisciplinary approach to rehabilitation. This entails addressing key factors that impact recovery such as sleep. CNS has opened sleep laboratories within the residential buildings of our programs in Dallas, Texas and Bakersfield, California. All CNS facilities can arrange for a sleep evaluation at one of the labs, based on a patient’s needs and treatment plan. Sleep evaluations of CNS patients allow for the detection of sleep-related issues that are likely to hinder recovery. CNS sleep facilities also provide research opportunities to deepen understanding of sleep-related issues after brain injury. Findings from these studies will help improve treatment and develop new therapeutic strategies.

 

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[JUST ACCEPTED] “Increased Sensorimotor Cortex Activation with Decreased Motor Performance during Functional Upper Extremity Tasks Post-Stroke” – Abstract

The following article has just been accepted for publication in Journal of Neurologic Physical Therapy.

“Increased Sensorimotor Cortex Activation with Decreased Motor Performance during Functional Upper Extremity Tasks Post-Stroke”

By Shannon B Lim, MSc, MPT; Janice J Eng

Provisional Abstract:

Background: Current literature has focused on identifying neuroplastic changes associated with stroke through tasks and in positions that are not representative of functional rehabilitation. Emerging technologies such as functional near-infrared spectroscopy (fNIRS) provide new methods of expanding the area of neuroplasticity within rehabilitation.
Purpose: This study determined the differences in sensorimotor cortex activation during unrestrained reaching and gripping after stroke.
Methods: 11 healthy and 11 chronic post-stroke individuals completed reaching and gripping tasks under three conditions using their 1) stronger, 2) weaker, and 3) both arms together. Performance and sensorimotor cortex activation using fNIRS were collected. Group and arm differences were calculated using mixed ANCOVA (covariate: age). Pairwise comparisons were used for post-hoc analyses. Partial Pearson’s correlations between performance and activation were assessed for each task, group, and hemisphere.
Results: Larger sensorimotor activations in the ipsilesional hemisphere were found for the stroke compared to healthy group for reaching and gripping conditions despite poorer performance. Significant correlations were observed between gripping performance (with the weaker arm and both arms simultaneously) and sensorimotor activation for the stroke group only.
Discussion: Stroke leads to significantly larger sensorimotor activation during functional reaching and gripping despite poorer performance. This may indicate an increased sense of effort, decreased efficiency, or increased difficulty after stroke.
Conclusion: fNIRS can be used for assessing differences in brain activation during movements in functional positions after stroke. This can be a promising tool for investigating possible neuroplastic changes associated with functional rehabilitation interventions in the stroke population.

Supplemental Digital Content 1. Video abstract .mp4

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[NEWS] Stroke: Rewiring eye-brain connection may restore vision

Many people who have a stroke also experience vision impairment as a result. New groundbreaking research looks at the mechanisms that play a role in this damage and shows that it may be reversible.

a person's eye looking up

New research may offer people who have lost some of their vision due to a stroke renewed hope that they may regain it.

A stroke can affect different parts of the brain. When it occurs in the primary visual cortex, which is the region of the brain that processes visual information, the lack of oxygenated blood can mean that the neurons (brain cells) active in that region incur damage.

In turn, this will affect people’s ability to see, and they may experience various degrees of vision loss. While some people who experience vision loss after a stroke may spontaneously regain their sight, most individuals do not.

So far, specialists have believed that damage to the primary visual cortex neurons causes a set of cells in the eye’s retina called “retinal ganglion cells” to become atrophied, meaning that they lose their ability to function.

When retinal ganglion cells become atrophied, it is highly unlikely that a person will ever recover sight in the affected area.

However, a new study, the findings of which appear in the journal Proceedings of the Royal Society B, has uncovered more information about the brain damage mechanisms relating to impaired eyesight.

“The integration of a number of cortical regions of the brain is necessary in order for visual information to be translated into a coherent visual representation of the world,” explains study co-author Dr. Bogachan Sahin, Ph.D., who is an assistant professor at the University of Rochester Medical Center in New York.

“And while the stroke may have disrupted the transmission of information from the visual center of the brain to higher order areas,” he adds, “these findings suggest that when the primary visual processing center of the brain remains intact and active, clinical approaches that harness the brain’s plasticity could lead to vision recovery.”

Therapies should ‘encourage neuroplasticity’

In the new study, the researchers worked with 15 participants who were receiving care at Strong Memorial and Rochester General Hospital for vision damage resulting from a stroke.

The participants agreed to take tests assessing their eyesight. They also had MRI scans to monitor their brain activity and an additional test that looked at the state of the retinal ganglion cells.

First, the investigators found that the health and survival of the retinal ganglion cells were highly dependent on activity in the associated primary visual area. Thus, the retinal cells connected to inactive brain areas would atrophy.

At the same time, however, the team surprisingly noted that some retinal cells in the eyes of people who had experienced vision impairment were still healthy and functional, even though the person had lost sight in that part of the eye.

This finding, the researchers explain, indicates that those healthy eye cells remained connected to fully active brain cells in the visual cortex. However, the neurons failed to correctly interpret the visual information that they received from the corresponding retinal ganglion cells, so the stimuli did not “translate” into sight.

“These findings suggest a treatment protocol that involves a visual field test and an eye exam to identify discordance between the visual deficit and retinal ganglion cell degeneration,” notes the study’s first author Dr. Colleen Schneider.

“This could identify areas of vision with intact connections between the eyes and the brain, and this information could be used to target visual retraining therapies to regions of the blind field of vision that are most likely to recover,” Dr. Schneider adds.

In the future, the researchers hope that their current discovery will allow specialists to fine-tune current therapeutic approaches or develop better strategies that will stimulate the damaged brain-eye connections to “rewire” correctly.

“This study breaks new ground by describing the cascade of processes that occur after a stroke in the visual center of the brain and how this ultimately leads to changes in the retina,” says senior author Brad Mahon, Ph.D.

By more precisely understanding which connections between the eye and brain remain intact after a stroke, we can begin to explore therapies that encourage neuroplasticity with the ultimate goal of restoring more vision in more patients.”

Brad Mahon, Ph.D.

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[WEB SITE] The Adult Brain Does Grow New Neurons After All, Study Says

Study points toward lifelong neuron formation in the human brain’s hippocampus, with implications for memory and disease

The Adult Brain Does Grow New Neurons After All, Study Says

Cerebral cortical neuron. Credit: Getty Images

If the memory center of the human brain can grow new cells, it might help people recover from depression and post-traumatic stress disorder (PTSD), delay the onset of Alzheimer’s, deepen our understanding of epilepsy and offer new insights into memory and learning. If not, well then, it’s just one other way people are different from rodents and birds.

For decades, scientists have debated whether the birth of new neurons—called neurogenesis—was possible in an area of the brain that is responsible for learning, memory and mood regulation. A growing body of research suggested they could, but then a Nature paper last year raised doubts.

Now, a new study published today in another of the Nature family of journals—Nature Medicine—tips the balance back toward “yes.” In light of the new study, “I would say that there is an overwhelming case for the neurogenesis throughout life in humans,” Jonas Frisén, a professor at the Karolinska Institute in Sweden, said in an e-mail. Frisén, who was not involved in the new research, wrote a News and Views about the study in the current issue of Nature Medicine.

Not everyone was convinced. Arturo Alvarez-Buylla was the senior author on last year’s Nature paper, which questioned the existence of neurogenesis. Alvarez-Buylla, a professor of neurological surgery at the University of California, San Francisco, says he still doubts that new neurons develop in the brain’s hippocampus after toddlerhood.

“I don’t think this at all settles things out,” he says. “I’ve been studying adult neurogenesis all my life. I wish I could find a place [in humans] where it does happen convincingly.”

For decades, some researchers have thought that the brain circuits of primates—including humans—would be too disrupted by the growth of substantial numbers of new neurons. Alvarez-Buylla says he thinks the scientific debate over the existence of neurogenesis should continue. “Basic knowledge is fundamental. Just knowing whether adult neurons get replaced is a fascinating basic problem,” he said.

New technologies that can locate cells in the living brain and measure the cells’ individual activity, none of which were used in the Nature Medicinestudy, may eventually put to rest any lingering questions.

A number of researchers praised the new study as thoughtful and carefully conducted. It’s a “technical tour de force,” and addresses the concerns raised by last year’s paper, says Michael Bonaguidi, an assistant professor at the University of Southern California Keck School of Medicine.

The researchers, from Spain, tested a variety of methods of preserving brain tissue from 58 newly deceased people. They found that different methods of preservation led to different conclusions about whether new neurons could develop in the adult and aging brain.

Brain tissue has to be preserved within a few hours after death, and specific chemicals used to preserve the tissue, or the proteins that identify newly developing cells will be destroyed, said Maria Llorens-Martin, the paper’s senior author. Other researchers have missed the presence of these cells, because their brain tissue was not as precisely preserved, says Llorens-Martin, a neuroscientist at the Autonomous University of Madrid in Spain.

Jenny Hsieh, a professor at the University of Texas San Antonio who was not involved in the new research, said the study provides a lesson for all scientists who rely on the generosity of brain donations. “If and when we go and look at something in human postmortem, we have to be very cautious about these technical issues.”

Llorens-Martin said she began carefully collecting and preserving brain samples in 2010, when she realized that many brains stored in brain banks were not adequately preserved for this kind of research. In their study, she and her colleagues examined the brains of people who died with their memories intact, and those who died at different stages of Alzheimer’s disease. She found that the brains of people with Alzheimer’s showed few if any signs of new neurons in the hippocampus—with less signal the further along the people were in the course of the disease. This suggests that the loss of new neurons—if it could be detected in the living brain—would be an early indicator of the onset of Alzheimer’s, and that promoting new neuronal growth could delay or prevent the disease that now affects more than 5.5 million Americans.

Rusty Gage, president of the Salk Institute for Biological Studies and a neuroscientist and professor there, says he was impressed by the researchers’ attention to detail. “Methodologically, it sets the bar for future studies,” says Gage, who was not involved in the new research but was the senior author in 1998 of a paper that found the first evidence for neurogenesis. Gage says this new study addresses the concerns raised by Alvarez-Buylla’s research. “From my view, this puts to rest that one blip that occurred,” he says. “This paper in a very nice way… systematically evaluates all the issues that we all feel are very important.”

Neurogenesis in the hippocampus matters, Gage says, because evidence in animals shows that it is essential for pattern separation, “allowing an animal to distinguish between two events that are closely associated with each other.” In people, Gage says, the inability to distinguish between two similar events could explain why patients with PTSD keep reliving the same experiences, even though their circumstances have changed. Also, many deficits seen in the early stages of cognitive decline are similar to those seen in animals whose neurogenesis has been halted, he says.

In healthy animals, neurogenesis promotes resilience in stressful situations, Gage says. Mood disorders, including depression, have also been linked to neurogenesis.

Hsieh says her research on epilepsy has found that newborn neurons get miswired, disrupting brain circuits and causing seizures and potential memory loss. In rodents with epilepsy, if researchers prevent the abnormal growth of new neurons, they prevent seizures, Hsieh says, giving her hope that something similar could someday help human patients. Epilepsy increases someone’s risk of Alzheimer’s as well as depression and anxiety, she says. “So, it’s all connected somehow. We believe that the new neurons play a vital role connecting all of these pieces,” Hsieh says.

In mice and rats, researchers can stimulate the growth of new neurons by getting the rodents to exercise more or by providing them with environments that are more cognitively or socially stimulating, Llorens-Martin says. “This could not be applied to advanced stages of Alzheimer’s disease. But if we could act at earlier stages where mobility is not yet compromised,” she says, “who knows, maybe we could slow down or prevent some of the loss of plasticity [in the brain].”


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The Adult Brain Does Grow New Neurons After All, Study Says – Scientific American

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[ARTICLE] Guided Self-rehabilitation Contract vs conventional therapy in chronic stroke-induced hemiparesis: NEURORESTORE, a multicenter randomized controlled trial – Full Text

Abstract

Background

After discharge from hospital following a stroke, prescriptions of community-based rehabilitation are often downgraded to “maintenance” rehabilitation or discontinued. This classic therapeutic behavior stems from persistent confusion between lesion-induced plasticity, which lasts for the first 6 months essentially, and behavior-induced plasticity, of indefinite duration, through which intense rehabilitation might remain effective. This prospective, randomized, multicenter, single-blind study in subjects with chronic stroke-induced hemiparesis evaluates changes in active function with a Guided Self-rehabilitation Contract vs conventional therapy alone, pursued for a year.

Methods

One hundred and twenty four adult subjects with chronic hemiparesis (> 1 year since first stroke) will be included in six tertiary rehabilitation centers. For each patient, two treatments will be compared over a 1-year period, preceded and followed by an observational 6-month phase of conventional rehabilitation. In the experimental group, the therapist will implement the diary-based and antagonist-targeting Guided Self-rehabilitation Contract method using two monthly home visits. The method involves: i) prescribing a daily antagonist-targeting self-rehabilitation program, ii) teaching the techniques involved in the program, iii) motivating and guiding the patient over time, by requesting a diary of the work achieved to be brought back by the patient at each visit. In the control group, participants will benefit from conventional therapy only, as per their physician’s prescription.

The two co-primary outcome measures are the maximal ambulation speed barefoot over 10 m for the lower limb, and the Modified Frenchay Scale for the upper limb. Secondary outcome measures include total cost of care from the medical insurance point of view, physiological cost index in the 2-min walking test, quality of life (SF 36) and measures of the psychological impact of the two treatment modalities. Participants will be evaluated every 6 months (D1/M6/M12/M18/M24) by a blinded investigator, the experimental period being between M6 and M18. Each patient will be allowed to receive any medications deemed necessary to their attending physician, including botulinum toxin injections.

Discussion

This study will increase the level of knowledge on the effects of Guided Self-rehabilitation Contracts in patients with chronic stroke-induced hemiparesis.

Background

The most common motor deficit following stroke is spastic hemiparesis [1]. More than 90% of patients with hemiparesis recover some lower limb function after a stroke, but rarely with a level of ease or speed that would allow for independent and comfortable ambulation in everyday life, outdoors in particular [123]. In the upper limb, the proportion of patients that recover daily use of the arm is estimated between 10 and 30% [45678]. Consequently, around half of stroke survivors do not resume professional activities, and two thirds remain chronically disabled [9].

In parallel, most patients in chronic stages have their rehabilitation discontinued or converted into “maintenance” therapy, as professionals often estimate that they might no longer progress [7101112131415]. Others benefit from reinduction periods, prescribed according to subjective or ill-defined criteria. It has not been demonstrated that this conventional rehabilitation system now fits current knowledge on behavior-induced brain plasticity and on the potential for motor recovery in chronic spastic paresis [161718]. Indeed, a significant body of evidence demonstrates that high intensity of rehabilitation (the opposite of “maintenance therapy”) correlates with motor function improvement in chronic stages [161920]. One way to achieve sufficient amounts of physical treatment might be to adequately guide and motivate the patient into practicing self-rehabilitation [1820]. It has been confirmed that programs of exercises given by the therapist to be performed at home are appreciated by patients not only for the structure they give to everyday life, but also as they represent in themselves a source of motivation and hope, particularly when these programs are associated with ongoing professional support [2122].

We hypothesize that there is confusion between the lesion-induced plasticity of the central nervous system – essentially during the first 6 months post-lesion – and the behavior-induced plasticity, which lasts indefinitely [16172324252627]. The latter justifies initiatives to organize chronic and intense physical rehabilitation work [1718232425262728]. Even though previous, short-term open studies evaluating self-rehabilitation programs in spastic hemiparesis suggested the possibility of functional improvement, to our knowledge there are no large-scale prospective randomized controlled protocols that test the effectiveness of long term self-rehabilitation programs in spastic hemiparesis as against conventional rehabilitation systems, especially in chronic stages [2930313233343536].

Technically, which home rehabilitation exercises might be recommended? From a neurophysiological point of view, muscle overactivity chronologically emerges as the third fundamental feature of motor impairment that begins in the subacute phase in hemiparesis, following paresis and soft tissue contracture that appear in the acute phase [373839]. One recognizable form of muscle overactivity is spasticity (hyper-reflectivity to phasic stretch), which is potentiated by muscle shortening [3738]. Hypersensitivity to stretch in an antagonist muscle also impedes voluntary motoneurone recruitment for the agonist muscle, a phenomenon called “stretch-sensitive paresis” [40]. As none of the three fundamental mechanisms of motor impairment (paresis, muscle shortening, and muscle overactivity) is distributed symmetrically between agonists and antagonists, there are force imbalances around joints, hindering active movements and deforming body postures [41]. Each of these three mechanisms of impairment, particularly the two most important, which are muscle shortening and muscle overactivity, can be specifically targeted with local treatment, muscle by muscle, aiming to rebalance forces, joint by joint [28]. For the less overactive muscles around each joint, an intensive motor training will aim to break the vicious cycle Paresis-Disuse-Paresis [37]. For their shortened and more overactive antagonists most importantly, a daily program of self-stretch postures at high load combined with a program of maximal amplitude rapid alternating movements, potentially associated with botulinum toxin injections, will aim to increase muscle extensibility and reduce cocontraction, breaking the vicious cycle: Muscle shortening-Overactivity-Muscle shortening [284243] (www.i-gsc.com). Significant preliminary results obtained using prescription and teaching of self-rehabilitation programs within a Guided Self-rehabilitation Contract (GSC) led us to hypothesize that this method practiced over the long term might enhance active motor function in chronic hemiparesis beyond 1 year following stroke [184445464748].

From a social point of view, stroke is the leading cause of acquired disability in Western countries. For the Steering Committee on Stroke Prevention and Management in France, the yearly cost of stroke is €5.9 billions, the cost of care in medical and social facilities is €2.4 billions and the cost of daily allowances and disability pensions is €125.8 millions [49]. Additionally, several studies have shown that indirect costs were proportional to direct costs [50]. Stroke thus accounts for a large share of health expenditures. In that regard as well, devising a feasible and effective guided self-rehabilitation program might offer financial advantages for our health systems.[…]

 

Continue —> Guided Self-rehabilitation Contract vs conventional therapy in chronic stroke-induced hemiparesis: NEURORESTORE, a multicenter randomized controlled trial | BMC Neurology | Full Text

Fig. 2

Fig. 2Template of diary in Guided Self-rehabilitation Contract

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[NEWS] Thunderbirds fund cutting-edge rehab enhancements for Barrow

Above: The Thunderbirds Charities gift to Barrow Neurological Foundation is being used to acquire four new devices, similar to this robotic hand. These instruments enable therapists at the Barrow Neuro-Robotics Rehabilitation Center to personalize therapy based on a patient’s abilities.

Patients recovering from stroke, traumatic brain and spine injuries will now have a leg up in their recovery journeys, thanks to a $350,000 grant from Thunderbirds Charities to Barrow Neurological Foundation.
An estimated 13.8 million Americans live with a disability caused by a brain or spinal cord injury, and each year, Barrow records more than 30,000 outpatient visits in the Neuro-Rehabilitation Center.

With this gift from Thunderbirds Charities, Barrow will acquire four cutting-edge devices for its Neuro-Robotics Rehabilitation Center, which provides personalized therapy to deliver better outcomes in less time. These robotics include:

• A body weight-supported treadmill that uses augmented and virtual reality to simulate challenges in everyday life, such as walking a golf course.

• A robot-assisted shoulder and arm rehabilitation device with intelligent gravity compensation and virtual reality to work on skills needed for daily function.

• A sensor-based device used to work on balance and posture training.

• An interactive surface for upper extremity, cognitive and sensory retraining to allow patients to practice motor skills.

Barrow has been at the forefront in the use of robotics, which mimic normal human movements and can be programmed to support or challenge a patient’s abilities. Many of these devices incorporate an interactive component, creating a game-like experience for the patient to conquer.

“These new robotics will help Barrow patients relearn how to stand, walk and perform skills that many take for granted, while also providing our therapists with more advanced tools to monitor progress,” said Katie Cobb, president of Barrow Neurological Foundation. “We want to thank Thunderbirds Charities for providing these life-changing tools for our patients’ continued recovery.”

“Barrow’s Neuro-Robotics Rehabilitation Center is making a positive, profound impact on the health of patients recovering from severe and debilitating injuries, and we are honored to be able to support such a great mission,” said Carlos Sugich, President of Thunderbirds Charities.

via Thunderbirds fund cutting-edge rehab enhancements for Barrow | AZ Big Media

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[NEWS] Vitamin D Deficiency Linked to Loss in Brain Plasticity

Feb 21, 2019 | Original Press Release from the University of Queensland

Vitamin D Deficiency Linked to Loss in Brain Plasticity

Perineuronal nets (bright green) surround particular neurons (blue). Fluorescence labelling reveals just how detailed these structures are. Credit: Phoebe Mayne, UQ

University of Queensland research may explain why vitamin D is vital for brain health, and how deficiency leads to disorders including depression and schizophrenia.

 

via Vitamin D Deficiency Linked to Loss in Brain Plasticity | Technology Networks

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