Posts Tagged Brain plasticity

[ARTICLE] Virtual reality-based treatment for regaining upper extremity function induces cortex grey matter changes in persons with acquired brain injury – Full Text

Abstract

Background

Individuals with acquired brain injuries (ABI) are in need of neurorehabilitation and neurorepair. Virtual anatomical interactivity (VAI) presents a digital game-like format in which ABI survivors with upper limb paresis use an unaffected limb to control a standard input device and a commonplace computer mouse to control virtual limb movements and tasks in a virtual world.

Methods

In a prospective cohort study, 35 ambulatory survivors of ABI (25/71% stroke, 10/29% traumatic brain injury) were enrolled. The subjects were divided into three groups: group A received VAI therapy only, group B received VAI and physical/occupational therapy (P/OT), and group C received P/OT only. Motor skills were evaluated by muscle strength (hand key pinch strength, grasp, and three-jaw chuck pinch) and active range of motion (AROM) of the shoulder, elbow, and wrist. Changes were analyzed by ANOVA, ANCOVA, and one-tailed Pearson correlation analysis. MRI data was acquired for group A, and volumetric changes in grey matter were analyzed using voxel-based morphometry (VBM) and correlated with quantified motor skills.

Results

AROM of the shoulder, elbow, and wrist improved in all three groups. VBM revealed grey matter increases in five brain areas: the tail of the hippocampus, the left caudate, the rostral cingulate zone, the depth of the central sulcus, and the visual cortex. A positive correlation between the grey matter volumes in three cortical regions (motor and premotor and supplementary motor areas) and motor test results (power and AROM) was detected.

Conclusions

Our findings suggest that the VAI rehabilitation program significantly improved motor function and skills in the affected upper extremities of subjects with acquired brain injuries. Significant increases in grey matter volume in the motor and premotor regions of affected hemisphere and correlations of motor skills and volume in nonaffected brain regions were present, suggesting marked changes in structural brain plasticity.

Background

Neurological disorders, including acquired brain injuries (ABIs) are important causes of disability and death worldwide [12]. Although age-standardized mortality rates for ischemic and hemorrhagic strokes have decreased in the past two decades, the absolute number of stroke survivors is increasing, with most of the burden in low- and middle-income countries [3]. Another major issue is that trends toward increasing stroke incidence at younger ages has been observed [4]. Moreover, this type of ABI is the leading cause of long-term disability in the United States, with an estimated incidence of 795,000 strokes yearly [2].

In more than 80% of stroke survivors, impairments are seen in at least one of the upper limbs. Six months after a stroke, 38% of patients recover some dexterity in the paretic arm, though only 12% recover substantial function even in spite of having received physical/occupational therapy (P/OT) [5]. Only a few survivors are able to regain some useful function of the upper limb. Failing to achieve useful function has highly negative impacts on the performance of daily living activities [67]. Regaining control and improving upper limb motor function after ABIs are therefore crucial goals of motor system rehabilitation. In left-sided limb impairment, neglect syndrome can contribute to a worsened clinical state, making the alleviation of symptoms even more difficult to achieve. Mirror therapy has been reported as a promising approach to improve neglect symptoms [89].

MRI has been used to track changes in brain connectivity related to rehabilitation [10], and several studies of healthy individuals playing off-the-shelf video games have demonstrated changes in the human brain resulting from interactions in a virtual world (VW) [1112]. Furthermore, playing video games results in brain changes associated with regaining improved, purposeful physical movements [1314]. The socio-cultural relevance of virtual reality (VR) and VW applications lies, more generally, in the fact that these technologies offer interactive environments to users. These interactive environments are actually present in the users’ experiences while less so in the world they share as biological creatures [15]. The way in which we engage with VWs allows for rehabilitation exercises and activities that feel similar to their actual physical world counterparts [11]. In the past two decades, researchers have demonstrated the potential for the interactive experiences of VWs to provide engaging, motivating, less physically demanding, and effective environments for ABI rehabilitation [916,17,18].

One of the suitable rehabilitation methods seems to be exercises and tasks in VW called virtual anatomical interactivity (VAI) [19]. This method provides sensory stimulation / afferent feedback and allows the independent control of an anatomically realistic virtual upper extremity capable of simulating human movements with a true range of motion. ABI survivors are able to relearn purposeful physical movements and regain movement in their disabled upper extremities [19]. Contrary to conventional therapy, which exercises impaired upper limbs to improve limb movement, the general VAI hypothesis is that brain exercises alone (or combined with traditional therapy) may positively influence neuroplastic functions. In the VW, subjects can move their virtual impaired limbs using their healthy hands, meaning simulated physical movements are survivor-authored. Virtual visuomotor feedback may help regain functional connectivity between the brain and the impaired limb, therefore also regaining voluntary control of the limb.

The aim of the study was to test if the shoulder, elbow, and wrist movement; hand pinch strength; and grip strength of the paretic side improved through the use of VAI exclusively or combined with P/OT for upper extremities and how these approaches improved functional outcomes measured by the Action Reach Arm Test [20]. The relationship between changes in abilities to control upper extremities and volumetric changes in cortex grey matter measured by VBM and using MRI was also explored.[…]

Continue —-> https://jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-020-00754-7

figure1
Examples of VAI games: multi-finger actions to pick up a spoon and drop it into a cup, tapping actions using the index and middle fingers on a remote control, removing a light bulb and reinserting it into another fixture designated by a letter of the alphabet, choosing letters of the alphabet to form words and phrases. All actions are performed by clicking and draging mouse on the appropriate body part

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[ARTICLE] The Promotoer, a brain-computer interface-assisted intervention to promote upper limb functional motor recovery after stroke: a study protocol for a randomized controlled trial to test early and long-term efficacy and to identify determinants of response – Full Text

Abstract

Background

Stroke is a leading cause of long-term disability. Cost-effective post-stroke rehabilitation programs for upper limb are critically needed. Brain-Computer Interfaces (BCIs) which enable the modulation of Electroencephalography (EEG) sensorimotor rhythms are promising tools to promote post-stroke recovery of upper limb motor function. The “Promotoer” study intends to boost the application of the EEG-based BCIs in clinical practice providing evidence for a short/long-term efficacy in enhancing post-stroke hand functional motor recovery and quantifiable indices of the participants response to a BCI-based intervention. To these aims, a longitudinal study will be performed in which subacute stroke participants will undergo a hand motor imagery (MI) training assisted by the Promotoer system, an EEG-based BCI system fully compliant with rehabilitation requirements.

Methods

This longitudinal 2-arm randomized controlled superiority trial will include 48 first ever, unilateral, subacute stroke participants, randomly assigned to 2 intervention groups: the BCI-assisted hand MI training and a hand MI training not supported by BCI. Both interventions are delivered (3 weekly session; 6 weeks) as add-on regimen to standard intensive rehabilitation. A multidimensional assessment will be performed at: randomization/pre-intervention, 48 h post-intervention, and at 1, 3 and 6 month/s after end of intervention. Primary outcome measure is the Fugl-Meyer Assessment (FMA, upper extremity) at 48 h post-intervention. Secondary outcome measures include: the upper extremity FMA at follow-up, the Modified Ashworth Scale, the Numeric Rating Scale for pain, the Action Research Arm Test, the National Institute of Health Stroke Scale, the Manual Muscle Test, all collected at the different timepoints as well as neurophysiological and neuroimaging measures.

Discussion

We expect the BCI-based rewarding of hand MI practice to promote long-lasting retention of the early induced improvement in hand motor outcome and also, this clinical improvement to be sustained by a long-lasting neuroplasticity changes harnessed by the BCI-based intervention. Furthermore, the longitudinal multidimensional assessment will address the selection of those stroke participants who best benefit of a BCI-assisted therapy, consistently advancing the transfer of BCIs to a best clinical practice.

Trial registration

Name of registry: BCI-assisted MI Intervention in Subacute Stroke (Promotoer).

Trial registration number: NCT04353297; registration date on the ClinicalTrial.gov platform: April, 15/2020.

Peer Review reports

Background

Stroke is a major public health and social care concern worldwide [1]. The upper limb motor impairment commonly persists after stroke, and it represents the major contribution to long-term disability [2]. It has been estimated that the main clinical predictor of whether a patient would come back to work is the degree of upper extremity function [3]. Despite the intensive rehabilitation, the variability in the nature and extent of upper limb recovery remains a crucial factor affecting rehabilitation outcomes [4].

Electroencephalography (EEG)-based Brain-Computer Interface (BCI) is an emerging technology that enables a direct translation of brain activity into motor action [5]. Recently, EEG-based BCIs have been recognized as potential tools to promote functional motor recovery of upper limbs after stroke (for review see [6]). Several randomized controlled trials have shown that stroke patients can learn to modulate their EEG sensorimotor rhythms [7] to control external devices and this practice might facilitate neurological recovery both in subacute and chronic stroke phase [8,9,10].

We were previously successful in the design and validation of an EEG sensorimotor rhythms–based BCI combined with realistic visual feedback of upper limb to support hand motor imagery (MI) practice in stroke patients [1112]. Our previous pilot randomized controlled study [8] with the participation of 28 subacute stroke patients with severe motor deficit, suggested that 1 month BCI-assisted MI practice as an add-on intervention to the usual rehabilitation care was superior with respect to the add-on, 1 month MI training alone (ie., without BCI support) in improving hand functional motor outcomes (indicated by the significantly higher mean score at upper extremity Fugl-Meyer scale in the BCI with respect to control group). A greater involvement of the ipsilesional hemisphere, as reflected by a stronger motor-related EEG oscillatory activity and connectivity in response to MI of the paralyzed trained hand was also observed only in the BCI-assisted MI training condition. These promising findings corroborated the idea that a relatively low-cost technique (i.e. EEG-based BCI) can be exploited to deliver an efficacious rehabilitative intervention such as MI training and prompted us to undertake a translational effort by implementing an all-in-one BCI-supported MI training station– the Promotoer [13].

Yet, important questions remain to be addressed in order to improve the clinical viability of BCIs such as defining whether the expected early improvements in functional motor outcomes induced by the BCI-assisted MI training in subacute stroke [8] can be sustained in a long-term as it has been shown for other BCI-based approaches in chronic stroke patients [1014]. This requires advancements in the knowledge on brain functional re-organization early after stroke and on how this re-organization would correlate with the functional motor outcome (evidence-base medicine). Last but not least, the definition of the determinants of the patients response to treatment is paramount to optimize the process of personalized medicine in rehabilitation. We will address these questions by carrying out a randomized trial to eventually establish the fundamentals for a cost-effective use of EEG-based BCI technology to deliver a rehabilitative intervention such as the MI in hospitalized stroke patients.

Aim and hypotheses

The “Promotoer” study is a randomized controlled trial (RCT) designed to provide evidence for a significant early improvement of hand motor function induced by the BCI-assisted MI training operated via the Promotoer and for a persistency (up to 6 months) of such improvement. Task-specific training was reported to induce long-term improvements in arm motor function after stroke [15,16,17]. Thus, our hypothesis is that the BCI-based rewarding of hand MI tasks would promote long-lasting retention of early induced positive effect on motor performance with respect to MI tasks practiced in an open loop condition (ie, without BCI). Accordingly, the primary aim of the “Promotoer” RCT will be first to determine whether the BCI based intervention (MI-BCI) administered by means of a BCI system fully compatible with a clinical setting (the Promotoer), is superior to a non-BCI assisted MI training (MI Control) in improving hand motor function outcomes in sub-acute stroke patients admitted to the hospital for their standard rehabilitation care; secondly, we will test whether the efficacy of BCI-based intervention on hand motor function outcomes is sustained long-term after the end of intervention (6 months follow-up). A further hypothesis is that such clinical improvement would be sustained by a long-lasting neuroplasticity changes as harnessed by the BCI–based intervention. This hypothesis rises from current evidence for an early enhancement of post-stroke plastic changes enabled by BCI-based trainings [8,9,10]. To test this hypothesis, a longitudinal assessment of the brain network organization derived from advanced EEG signal processing (secondary objective) will be performed.

The heterogeneity of stroke makes prediction of treatment responders a great challenge [18]. The potential value of a combination of neurophysiological and neuroimaging biomarkers with the clinical assessment in predicting post-stroke motor recovery has been recently highlighted [19]. Our hypothesis is that the longitudinal combined functional, neurophysiological and neuroimaging assessment over 6 months from the intervention will allow for insights into biomarkers and potential predictors of patients response to the BCI-Promotoer training (secondary aim). To this purpose, well-recognized factors contributing to recovery after stroke such as the relation between clinical profile, lesion characteristics and patterns of post-stroke motor cortical re-organization (eg., ipsilesional/contralesional primary and non-primary motor areas, cortico-spinal tract integrity, severity of motor deficits at baseline; for review see [19]) will be taken into account.[…}

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figure2
The Promotoer system. The Promoter is equipped with a computer, a commercial wireless EEG/EMG system (g.MOBIlab, g.tec medical engineering GmbH Austria), a screen for the therapist feedback (for the electroencephalographic – EEG activity and electromyographic- EMG activity monitoring) and screen for the ecological feedback to the participant; this ecological feedback is delivered by means of a custom software program that provides for (personalized) visual representation of the participant’s own hands. As such, this software allows the therapists to create an artificial reproduction of a given participant’s hand and forearm by adjusting a digitally created image in shape, size, skin color and orientation to match as much as possible the real hand and arm of the participant. Real-time feedback is provided by means of BCI2000 software [40]. The degree of EEG desynchronization over selected electrodes within selected frequencies (BCI control features) determines the vertical velocity of the cursor on the therapist’s screen and it operates the “virtual” hand software accordingly. The image is original as it is owned by the authors

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[VIDEO] Managing Fatigue After A Brain Injury – YouTube

via Managing Fatigue After A Brain Injury – YouTube

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[VIDEO] How brain plasticity can change your life with Michael Merzenich at Mind & Its Potential 2014 – YouTube

Hear the latest on how the brain develops and how positive and negative brain plasticity remodels the brain across the lifespan. Learn how to evaluate your own brain and how to rejuvenate, remodel and reshape your brain at any age.

Professor Michael Merzenich, USA, world’s foremost expert on the science of brain training who featured in ABC TV hit series Redesign My Brain as Todd Sampson’s brain training mentor; author of Soft-Wired: How The New Science of Brain Plasticity Can Change Your Life

For more information visit http://www.happinessanditscauses.com.au

 

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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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[WEB SITE] Vagus Nerve Stimulation Enhances Brain Plasticity

Sebastian Kaulitzki/Shutterstock

Vagus nerve illustrated in yellow.
Source: Sebastian Kaulitzki/Shutterstock

Vagus nerve stimulation (VNS) enhances targeted neuroplasticity, helping the brain build stronger neural connections after a stroke, according to pioneering research from the University of Texas at Dallas. Using an animal model, the researchers have demonstrated for the first time that pairing VNS with a physical therapy task accelerates the recovery of motor skills.

The researchers published their findings, “Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke Recovery,” in the journal Stroke. A human clinical trial of the same treatment, “Pivotal Study of VNS During Rehab After Stroke (VNS-REHAB),” is currently underway at 18 research sites across the US and in the UK. The goal of the study is to gauge the efficacy of paired vagus nerve stimulation in helping stroke patients recover motor skills more quickly.

What Is Vagus Nerve Stimulation?

Alila Medical Media/Shutterstock

Source: Alila Medical Media/Shutterstock

Vagus nerve stimulation is delivered via a small, surgically implanted device that uses electrical impulses of varying intensities and pulse-widths to activate the vagus nerve. Electrical stimulation of the vagus nerve using VNS is an FDA-approved treatment for drug-resistant epilepsy and treatment-resistant depression. A recent proof-of-concept human study also found that VNS is a viable treatment for inflammatory joint diseases such as rheumatoid arthritis.

The sudden loss of blood flow after a stroke causes neurons in any stroke-affected brain region to die, which cuts off connections to other nerve cells. The loss of motor skills in an arm or leg after a stroke is caused by a loss of connectivity between nerve cells in the limb with corresponding motor regions of the brain.

Using an animal model, the UT Dallas researchers found that brief bursts of VNS strengthen communication pathways by building stronger cell connections in the brain after a stroke. In fact, their results show that coupling VNS with targeted movement therapies dramatically boosts the benefit of rehabilitative training after a stroke. And, in animal studies, these improvements lasted for months after the completion of VNS targeted therapy.

As the authors of this study, led by Eric C. Meyers, explain: “This study provides the first evidence that VNS paired with rehabilitative training after stroke (1) doubles long-lasting recovery on a complex task involving forelimb supination, (2) doubles recovery on a simple motor task that was not paired with VNS, and (3) enhances structural plasticity in motor networks.”

Michael Kilgard, associate director of the Texas Biomedical Device Center and professor of neuroscience in the School of Behavioral and Brain Sciences at UT Dallas, was a senior co-author of this research. Kilgard is the principal investigator at the UTD Cortical Plasticity Laboratory. His teamalso includes Seth Hays, a postdoctoral researcher in the School of Behavioral and Brain Sciences at UT Dallas, who specializes in targeted plasticity therapy to alleviate motor dysfunction.

“Our experiment was designed to ask this new question: After a stroke, do you have to rehabilitate every single action?” Kilgard said in a statement. “If VNS helps you, is it only helping with the exact motion or function you paired with stimulation? What we found was that it also improves similar motor skills as well, and that those results were sustained months beyond the completion of VNS-paired therapy.”

The UT Dallas researchers are optimistic that their latest research on targeted vagus nerve stimulation is a pivotal step toward creating guidelines for standardized usage of VNS during post-stroke therapy in humans. “We have long hypothesized that VNS is making new connections in the brain, but nothing was known for sure,” Hays said in a statement. “This is the first evidence that we are driving changes in the brain in animals after brain injury. It’s a big step forward in understanding how the therapy works — this reorganization that we predicted would underlie the benefits of VNS.”

Another recent study from UT Dallas found that moderate intensity vagus nerve stimulation optimized the neuroplasticity-enhancing and memory-enhancing effects of VNS more effectively than low or high-intensity stimulation. Notably, the researchers pinpointed that the optimal pulse width and current intensity were marked by an “inverted-U” pattern in which too much or too little VNS was less effective than a ‘Goldilocks’ sweet spot of moderate intensity that was just right. These 2017 findings were published in the journal Brain Stimulation.

Paired Vagus Nerve Stimulation Offers New Hope for Stroke Rehabilitation

In 2017, the makers of a vagus nerve stimulation device launched a randomized, double-blind clinical trial of VNS rehab for patients after a cerebrovascular stroke. This study, currently underway, will include up to 120 subjects at 18 clinical locations across the US and in the UK. The estimated conclusion date of preliminary research for this clinical trial is June 30, 2019.

The Ohio State University is one of the institutions participating in the paired VNS clinical trial. Marcie Bockbrader of the Wexner Medical Center at OSU is their principal investigator for the trial.

In a recent press release, Bockbrader said: “This nerve stimulation is like turning on a switch, making the patient’s brain more receptive to therapy. The goal is to see if we can improve motor recovery in people who have what is, in effect, a brain pacemaker implanted in their body. The idea is to combine this brain pacing with normal rehab, and see if patients who’ve been through all of their other usual therapies after a stroke can get even better.”

Below is a YouTube video of Marcie Bockbrader and colleagues in their paired VNS therapy lab along with a patient describing his stroke rehab process:

For this clinical trial, each study participant receives three one-hour sessions of intensive physiotherapy per week for a total of six weeks. The goal is to improve task-specific motor arm function. Half of the group participating in this clinical trial had a vagus nerve stimulation device surgically implanted; the other half will serve as a control group.

During each rehabilitation therapy session, whenever a patient correctly performs a particular motor skill, the therapist pushes a button to trigger an optimal pulse width and current intensity of vagus nerve stimulation. The hypothesis is that if precise and accurate movements are positively reinforced by a brief burst of VNS during a trial-and-error learning process that these actions become “hardwired” into the brain more quickly.

“We are trying to see if this neurostimulator could be used to boost the effective therapy, creating a sort of ‘supercharged therapy.’ We want to determine if patients can recover more quickly through the use of this stimulation,” Bockbrader concluded.

References

Eric C. Meyers, Bleyda R. Solorzano, Justin James, Patrick D. Ganzer, Elaine S. Lai, Robert L. Rennaker, Michael P. Kilgard, Seth A. Hays. “Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke Recovery.” Stroke (First published online: January 25,  2018) DOI: 10.1161/STROKEAHA.117.019202

Kristofer W. Loerwald, Michael S. Borland, Robert L. Rennaker II, Seth A. Hays, Michael P. Kilgard. “The Interaction of Pulse Width and Current Intensity on the Extent of Cortical Plasticity Evoked by Vagus Nerve Stimulation.” Brain Stimulation (First published online: November 15, 2017) DOI: 10.1016/j.brs.2017.11.007

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[Editorial] Adult Neurogenesis: Beyond Rats and Mice – Neuroscience

Editorial on the Research Topic
Adult Neurogenesis: Beyond Rats and Mice

Most biological tissues routinely replace old cells with new ones. Unlike other tissues, the nervous system–being the most complex biological device found in nature–uniquely maintains most of its neurons throughout life and replaces relatively few. It preserves hotspots where it generates new neurons from resident stem cells during adulthood in a process known as adult neurogenesis, which varies among different species in its features, dynamics, and regulation. In spite of its widespread prevalence in the animal kingdom, the preponderance of studies conducted on a few laboratory rodent species such as rats and mice limits our understanding of the evolution, regulation, and function of adult neurogenesis. The anatomy, complexity and functions of the brain vary greatly in the animal kingdom: striking differences exist from simple bilaterians to humans, and, to a lesser extent, also among mammals. Therefore, both comparative and focused studies on different species will shed more light on the origin, development, and purpose of adult neurogenesis.

Adult neurogenesis was discovered and described by Joseph Altman and Das in rats (Altman and Das, 1965) and has been investigated in many species such as the zebrafish, frog, songbird, mole, mole-rat, vole, bat, fox, dog, dolphin, elephant, shrew, rabbit, monkey, and human. With the development of genetic manipulation techniques, researchers have focused largely on inbred laboratory rodents. While this provides a strong advantage of restricting genetic variation in the group, it also narrows our perspective on adult neurogenesis as a biological phenomenon (Bolker, 2017). Moreover, the rapid development of genetic tools has made Mus musculus the species of choice in studying adult neurogenesis. Yet, many unsolved issues and open questions cannot be resolved without the contribution of comparative studies spanning through widely different species. Such issues involve: how did adult neurogenesis evolve, whether our survival depend on adult neurogenesis, what is the link between adult neurogenesis and brain complexity, how do adult neurogenesis and animal behavior influence each other, how does adult neurogenesis contribute to brain plasticity, cognition and, possibly, repair, and how do experimental conditions affect adult neurogenesis.

Studying unconventional species will give us insights into the evolution and function of the brain, strengthening our understanding of the cellular basis of cognition and behavior, thus helping adult neurogenesis to find its place in the puzzle. With this Research Topic we, along with contributors from different areas, tried to answer the open questions and to encourage engaging discussions on the comparative and evolutionary aspects of adult neurogenesis. The diversity in adult neurogenesis indeed spans the de-novo formation of the entire adult brain in planaria (Brown and Pearson), neurogenesis in diverse brain areas in fish (Olivera-Pasilio et al.), reptiles (LaDage et al.Lutterschmidt et al.), and birds (Barkan et al.Kosubek-Langer et al.) to animals with restricted neurogenic niches such as invertebrates (Beltz and BentonSimões and Rhiner) and mammals (Taylor et al.Lévy et al.OosthuizenWiget et al.). The striking differences do not only concern the sites of occurrence and relative amounts (Brown and PearsonLévy et al.Olivera-Pasilio et al.Wiget et al.) but also in mechanistic aspects of stem cell biology. Intriguing examples are given by the adult-born neurons generated from the immune system and then traveling to the neurogenic niche via the circulatory system in the crayfish brain (Beltz and BentonSimões and Rhiner), or the heterogeneity of neoblasts, putative stem cells, in flatworms enabling the regeneration of the entire brain (Brown and Pearson). Yet, the main message from the comparative approach to adult neurogenesis is that the relative exclusive focus on laboratory rodents can result in a bias on how we think about this biological process. For instance, promising neuroprotective treatments developed in rodent models can fail in preclinical trials, and animal models with gyrencephalic brains might be necessary to study the behavior of neuroblasts in large white matter tracts (Taylor et al.). The bias is well-illustrated by the article of Faykoo-Martinez et al.: “species-specific adaptations in brain and behavior are paramount to survival and reproduction in diverse ecological niches and it is naive to think adult neurogenesis escaped these evolutionary pressures. A neuroethological approach to the study of adult neurogenesis is essential for a comprehensive understanding of the phenomenon.” Indeed, interactions of adult neurogenesis with neuroethological traits such as migration and mating behavior in snakes (Lutterschmidt et al.), territoriality in lizards (LaDage et al.), sociality and social interactions in mole-rats, birds, and sheep (Barkan et al.Lévy et al.Oosthuizen), or migratory lifestyle in birds (Barkan et al.) are presented here. The complexity of interactions is, to date, more an obstruction than a help in terms of publishability, but as Faykoo-Martinez et al. put it “most of us are guilty of making strong assertions about our data in order to have impact yet this ultimately creates bias in how work is performed, interpreted, and applied.” Such concerns are confirmed by the finding of remarkable reduction of adult neurogenesis in some large-brained, long-living mammals, including humans and dolphins (Sanai et al., 2011Sorrells et al., 2018), as reviewed and discussed in the article by Parolisi et al. More and more comparative data strongly support the view that adult neurogenesis is maintained in evolution only depending on strict relationships with its functional need(s). E.g., olfactory systems, mostly linked to paleocortical-hippocampal structures, were important in early mammalian evolution working as a reference system for spatial navigation for the location of food sources and mates, then replaced/integrated by the expansion of the isocortex as a “multimodal interface” for behavioral navigation based on vision and audition (Aboitiz and Montiel, 2015; see article by Parolisi et al.). The complex evolutionary aspects of adult neurogenesis role(s) and age-related reduction in mammals are addressed in the contribution by Hans-Peter Lipp. The main message of this opinion article is that no simple explanations can be called upon on such topic, a heavily actual conclusion even 30 years after neural stem cell discovery.

Animal models other than laboratory mice are by no means “out-of-reach” for advanced techniques, and the following examples could encourage and facilitate creative thinking in terms of research questions and how to approach them. Lindsey et al. present a thorough step-by-step protocol for visualizing cell proliferation in the whole zebrafish brain in 3 dimension. LaDage et al. used hormonal implants in lizards to study the interaction of testosterone and neurogenesis on territorial behavior. In fish and birds, Neurobiotin or lentivirus can be used to trace and characterize newly born neurons (Kosubek-Langer et al.Olivera-Pasilio et al.), and Brown and Pearson summarize the single-cell genomic data collected in planaria. Ideally, studies in laboratory rodents and non-conventional animal models can support and foster each other. For example, increased neurogenesis in laboratory mice confers stress resilience mediated by the temporal hippocampus (Anacker et al., 2018). Strikingly, wild rodents, naturally exposed to high stress levels, show more neurogenesis in the temporal hippocampus than the commonly used laboratory mouse C57BL/6 (Wiget et al.). Similarly, Reyes-Aguirre and Lamas identified the mechanism why the mouse retina cannot regenerate after damage, much in contrast to what has been reported in fish (Raymond et al., 2006). Finally, by using meta-analyses and a model to compare the neurodevelopmental sequences of different mammals, Charvet and Finlay try to put in a common time frame the envelopes of hippocampal neurogenesis, in order to interpret them in species with highly different lifespan.

In conclusion, with this Research Topic we strongly assert that adult neurogenesis research cannot rely exclusively on laboratory rodents, as each animal model can only cover certain aspects of the various flavors in which neuronal stem cells and their progeny in the postnatal brain can behave. The papers presented here emphasize the value of “… taking a step back and actually placing our results in a much larger, non-biomedical context, …[helping]… to reduce dogmatic thinking and create a framework for discovery” (Faykoo-Martinez et al.). After all, the failure of many clinical trials based on pre-clinical studies carried out on mice (Lindvall and Kokaia, 2010Donegà et al., 2013), do confirm the need for investments in comparative medicine (specifically on brain structural plasticity, see La Rosa and Bonfanti, 2018). A comparative view can indeed foster a more careful interpretation of the final impact of the biological process of neurogenesis in brain functioning and animal behavior.

References

Aboitiz, F., and Montiel, J. F (2015). Olfaction, navigation, and the origin of isocortex. Front. Neurosci. 9:402. doi: 10.3389/fnins.2015.00402

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Altman, J., and Das, G. D (1965). Post-natal origin of microneurones in the rat brain. Nature 207, 953–956. doi: 10.1038/207953a0

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Anacker, C., Luna, V. M., Stevens, G. S., Millette, A., Shores, R., Jimenez, J. C., et al. (2018). Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature 559, 98–102. doi: 10.1038/s41586-018-0262-4

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Bolker, J. A. (2017). Animal models in translational research: rosetta stone or stumbling block? Bioessays 39, 1–8. doi: 10.1002/bies.201700089

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Donegà, M., Giusto, E., Cossetti, C., and Pluchino, S (2013). “Systemic neural stem cell-based therapeutic interventions for inflammatory CNS disorders,” in Neural Stem Cells: New Perspectives, ed. L. Bonfanti (Rijeka: INTECH), 287–347.

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La Rosa, C., and Bonfanti, L (2018). Brain plasticity in mammals: An example for the role of comparative medicine in the Neurosciences. Front. Vet. Sci.5:274. doi: 10.3389/fvets.2018.00274

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Lindvall, O., and Kokaia, Z (2010). Stem cells in human neurodegenerative disorders-time for clinical translation? J. Clin. Invest. 120, 29–40. doi: 10.1172/JCI40543

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Keywords: comparative studies, evolution, brain plasticity, adult neurogenesis, brain repair, translation

via Frontiers | Editorial: Adult Neurogenesis: Beyond Rats and Mice | Neuroscience

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[Abstract] Simultaneous stimulation in bilateral leg motor areas with intermittent theta burst stimulation to improve functional performance after stroke: a feasibility pilot study

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BACKGROUND: Intermittent theta burst stimulation (iTBS) was widely used in stroke rehabilitation and was more efficient than repetitive transcranial magnetic stimulation in terms of inducing larger motor evoked potential and producing longer effects. To our knowledge, the outcomes are not available combining rehabilitation and iTBS for improving motor function of lower extremities in patients with stroke.
AIM: To evaluate the feasibility and effectiveness of intermittent theta burst stimulation aiming to stimulate bilateral leg motor cortex and promote functional improvements.
DESIGN: A single blind, randomized controlled pilot study.
SETTING: Rehabilitation ward.
POPULATION: Twenty patients with chronic stroke finally enrolled for analyzed.
METHODS: Participants were randomized into two groups to receive 10 sessions of iTBS group and sham group over a 5-week period. The iTBS was delivered over the midline of skull to stimulate bilateral leg motor cortex. The outcome measures included balance, mobility, and leg motor functions were measured before and after interventions.
RESULTS: Within-group differences were significant in the Berg Balance Scale for both groups (Z=-2.442, P=0.015 in iTBS group; Z=-2.094, P=0.036 in sham group), in the Fugl-Meyer Assessment (Z=-2.264, P=0.024) and Overall Stability Index of Biodex Balance System of iTBS group (Z=-2.124, P=0.034). However, no significant between-group differences were found.
CONCLUSIONS: There was no powerful evidence to support the effectiveness of iTBS group better than sham control group. Some essential technical issues should be considered for future studies applying iTBS to stimulate bilateral leg motor cortex.
CLINICAL REHABILITATION IMPACT: iTBS combined with stroke rehabilitation are probably expected to be useful for promote brain plasticity and functional performance but some technical issues should be carefully considered.

via Simultaneous stimulation in bilateral leg motor areas with intermittent theta burst stimulation to improve functional performance after stroke: a feasibility pilot study – European Journal of Physical and Rehabilitation Medicine 2018 Aug 27 – Minerva Medica – Journals

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[WEB SITE] 5 Secrets to Building Up Your Neuroplasticity

5 Secrets to Building Up Your Neuroplasticity

Up until recently, we believed our brain plasticity was stagnant and fixed. Dr. Norman Doige, a psychiatrist from the University of Toronto, helped to reveal that this isn’t the case. Neuroplasticity is something fluid that you can build up, and that means… you can create new neural pathways for the rest of your life. 5 Secrets to Building Up Your Neuroplasticity

Why is this important?

Like any other muscle in your body, when it comes to your brain, you either use it or lose it. To keep your cognition strong and to help set yourself up for successful aging, it’s important to create growth experiences for yourself that build up your neuroplasticity.

That’s why I’ve gathered these five secrets to help you build up your neuroplasticity:

1.  Set meaningful goals

Too often I meet seniors who’ve lived a life of duty, where they dedicated their lives to the hustle bustle of work, family and responsibilities. This is a completely honorable commitment.

The main fallback is… your dream list of meaningful goals oftentimes gets trapped in a hope chest and by the time retirement hits, maybe you’ve not only lost sight of your dream list but you’ve also lost interest in creating meaningful challenges for yourself.

One of the ways to increase your neuroplasticity is to create new and exciting challenges for yourself, and the way to create new and exciting challenges for yourself is to set meaningful goals.

What’s the best way to set meaningful goals?

Find clarity through some serious self-reflection. This can really help you uncover some of the passions that you have deep inside you, which ultimately can help create some of your most vibrant new neural pathways in your brain.

2.  Adopt a growth mindset

Once you have your meaningful goals, a powerful way to chase them and to keep your brain activated is to adopt a growth mindset.

A growth mindset is based on Dr. Carol Dweck’s idea that you can “grow your brain’s capacity to learn and solve problems.” It’s a perspective that believes you’re not born either smart or not-so-smart, but instead you’re born with the ability to learn.

The hard part?

It takes work. A critical ingredient of adopting a growth mindset is to embrace challenge. When we’re faced with any pitfalls and “fails” in life, especially when we’re willing to try something new and exciting, it’s easy to give up and run away from any challenges or roadblocks.

If you can learn the skill of learning and train yourself to look forward to those hard and challenging moments, you’ll be that much more likely to accomplish any of your personal goals.

Some more tips on developing a growth mindset:

  • Focus on the process and not the outcome– if you can get in the habit of enjoying the journey, you’ll be less focused on the destination, which in turn will allow your brain to better engage in the act of learning
  • Seek constructive criticism and not opinions– it’s a tough thing to let go of approval from others, but if you can instead learn to seek constructive feedback from other people, you’ll likely be more drawn to the learning process
  • Create a new goal for every goal that you complete– this’ll keep you in the mindset of lifelong learning and can help you continue to engage your brain over and over again in the long-term

3.  Tackle your goals using micro-steps

A powerful way to accomplish any goal is to break it down into smaller chunks I like to call micro-steps. This does four promising things for you:

  • It keeps you less overwhelmed by the big picture goal
  • It makes your goal more achievable and realistic
  • You’ll know exactly what to tackle next
  • It builds up your momentum and nurtures a habit of working consistently toward your goal

The most important takeaway from using micro-steps is that you want to get in the habit of being consistent in tackling each one. In order to make lasting changes in your brain pattern, you need to be diligent about giving yourself a learning process. Continue to challenge yourself on a regular basis. If setting and achieving new meaningful goals can become habitual, that’s when the neuroplasticity magic can happen for you.

4.  Be self-aware and mindful

According to Roberts Wesleyan College, you make nearly 35,000 decisions a day, which means a ton of those decisions are made while your brain is on autopilot. If you can learn to engage the decision-making part of your brain, your prefrontal cortex, you can increase your neuroplasticity.

A way to do this is to practice mindfulness so that you’re more self-aware and more likely to make value-based(vs autopilot) decisions throughout the day.

Researchers Bas Verplanken and Rob Holland found that people make value-based choices only when those values are cognitively activated.

Some ideas on how to practice mindfulness:

  • Meditate, practice yoga or do breathing exercises
  • Connect with nature and be more aware of your physical surroundings
  • Keep a journal and write about things you’re grateful for
  • Exercise regularly
  • Spend less time on digital devices and social media
  • Watch less TV

5.  Align your social circle with growth experiences

Your circle of influence is everything when it comes to how your daily habits are impacted. You become who you most spend time with so be sure to align your social circle with your personal goals and good habits.

There are stats that highlight the power of association, like these:

  • If your friend is obese, you’re 57% more likely to gain weight
  • If your friend gets a divorce, your chance for divorce goes up by 75%

By surrounding yourself with like-minded people who care about the same meaningful things that you do, you’re much more likely to continue to conquer your goals and expand your growth experiences. This is what’ll keep your neuroplasticity built-up and strong.

Tip: Spend less time with people in your area of concern, which is the area that highlights negativity, gossip, the news, the stock market, drama, regrets, fear, etc.

So there you have it – five practical tactics that’ll help you build up your brain health and neuroplasticity.

Which secret will you tackle first? How will you continue to create new and meaningful growth experiences for yourself?

via 5 Secrets to Building Up Your Neuroplasticity – Senior.com

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[WEB SITE] VR could trick stroke victims’ brains toward recovery.

Could virtual reality help stroke survivors regain motor function?

That’s a question Sook-Lei Liew is looking to answer.

Liew, an assistant professor at the University of Southern California and an affiliate of the Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine, was inspired by research from Mel Slater and Jeremy Bailenson on embodiment in VR. If someone’s given a child’s body in VR, for example, they might start exhibiting more childlike behavior.

She wondered if giving stroke survivors with motor impairments a virtual avatar that moves properly could help promote brain plasticity (or the ability to change) and recovery. Maybe it would eventually lead to them to moving an impaired limb again.

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USC researcher Sook-Lei Liew and her partners are testing to see whether virtual reality could help with stroke rehab. Nate Jense

“So, kind of like tricking the brain through visual input,” said Liew, who is also director of the Neural Plasticity and Neurorehabilitation Laboratory. “There’s a lot of emerging evidence from neuroscience and psychology that was showing that you can really identify [with the avatar], and it changes your behavior based on the avatar you’re given in VR.”

Virtual reality is a computer-generated simulation of a 3D environment. Using a VR headset with lenses that feed images to the eyes, a person can be virtually transported to another location, or interact with a setting in a seemingly realistic way. It’s commonly been used in gaming, but it’s being tested in other environments, too — like rehab.

Implementing VR in health care and patient treatment isn’t new. It’s been used to help people overcome phobias and anxiety disorders. But the application is starting to take off now that the technology is more developed and commercially available. Some medical schools are looking to train students with virtual simulations, and it’s even helping midwives learn how to deliver babies.

Liew’s research team has been working on a study for about two years called REINVENT, an acronym for Rehabilitation Environment using the Integration of Neuromuscular-based Virtual Enhancements for Neural Training. The researchers also collaborated with the USC Institute for Creative Technologies to develop the prototype.

The process works by using a brain-computer interface, which takes a signal from the brain and uses it to control another device: a computer, a robot or, in REINVENT’s case, an avatar in VR.

Next, researchers read electrical signatures of brain activity from the surface of the scalp using electroencephalography, or EEG, for short. The team also uses electromyography, which studies the electrical activity of the muscles. That can tell them whether somebody’s moving or if they’re trying to move.

Those signals are then fed into a program on a laptop. The program has thresholds so that when specific signals in the brain or muscle activity that correspond to an attempt to move are detected, they drive the movement of a virtual arm. The resulting visual feedback through a VR headset could help strengthen neural pathways from the damaged motor cortex to the impaired arm or limb.

While the researchers could theoretically extend this process to a patient’s lower limbs, Liew said it can be dangerous for someone with a motor impairment in the lower extremities to try to move with VR, so seated studies are much safer.

The research group recently finished testing the prototype using an Oculus DK2 with 22 healthy older adults, who provided a sample of what the brain and muscle signals look like when they move. They’re now starting to test with stroke patients in a controlled lab setting, aiming to work with 10 in the short term and hundreds in the long term, in both clinical and home environments.

The team also found that giving people neurofeedback of the virtual arm moving in a VR headset was more effective than simply showing it on a screen.

“Their brain activity in the motor regions that we’re trying to target is higher, and they’re able to control the brain-computer interface a little bit better and faster,” Liew said. “It makes the case that there is an added benefit from doing this in virtual reality, which is one of the first things we wanted to know.”

An unclear future

Because VR is still a relatively new technology, there are many unanswered questions on the best ways to use it in the medical profession.

“For the most part, nobody knows how to make great VR experiences, for business or consumer,” Gartner analyst Brian Blau said. “Over time, those issues will get resolved. But for the medical industry, they have the extra added bonus of having even more types of physical behaviors that they have to either mimic or want to measure.”

And while the possibilities for VR in health care are exciting, Liew is careful not to get ahead of herself.

“We think that VR is a promising medium, but we’re moving ahead cautiously,” she said. “A lot of the work that we’re trying to do is to test assumptions, because there’s a lot of excitement about VR, but there’s not that much that’s scientifically known.”

Only time — and plenty of research — will tell.

Tech Enabled: CNET chronicles tech’s role in providing new kinds of accessibility.

The Smartest Stuff: Innovators are thinking up new ways to make you, and the things around you, smarter.

via VR could trick stroke victims’ brains toward recovery-NewsCO.com.au – newsCO.com.au

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