Posts Tagged Neuroplasticity

[WEB SITE] Human brains make new nerve cells — and lots of them — well into old age.

Previous studies have suggested neurogenesis tapers off or stops altogether

BY
LAUREL HAMERS, APRIL 5, 2018
nerve cells in hippocampi

NEURON NURSERY  Roughly the same number of new nerve cells (dots) exist in the hippocampus of people in their 20s (three hippocampi shown, top row) as in people in their 70s (bottom). Blue marks the dentate gyrus, where new nerve cells are born.
M. BOLDRINI/COLUMBIA UNIV.

Your brain might make new nerve cells well into old age.

Healthy people in their 70s have just as many young nerve cells, or neurons, in a memory-related part of the brain as do teenagers and young adults, researchers report in the April 5 Cell Stem Cell. The discovery suggests that the hippocampus keeps generating new neurons throughout a person’s life.

The finding contradicts a study published in March, which suggested that neurogenesis in the hippocampus stops in childhood (SN Online: 3/8/18). But the new research fits with a larger pile of evidence showing that adult human brains can, to some extent, make new neurons. While those studies indicate that the process tapers off over time, the new study proposes almost no decline at all.

Understanding how healthy brains change over time is important for researchers untangling the ways that conditions like depression, stress and memory loss affect older brains.

When it comes to studying neurogenesis in humans, “the devil is in the details,” says Jonas Frisén, a neuroscientist at the Karolinska Institute in Stockholm who was not involved in the new research. Small differences in methodology — such as the way brains are preserved or how neurons are counted — can have a big impact on the results, which could explain the conflicting findings. The new paper “is the most rigorous study yet,” he says.

Researchers studied hippocampi from the autopsied brains of 17 men and 11 women ranging in age from 14 to 79. In contrast to past studies that have often relied on donations from patients without a detailed medical history, the researchers knew that none of the donors had a history of psychiatric illness or chronic illness. And none of the brains tested positive for drugs or alcohol, says Maura Boldrini, a psychiatrist at Columbia University. Boldrini and her colleagues also had access to whole hippocampi, rather than just a few slices, allowing the team to make more accurate estimates of the number of neurons, she says.

To look for signs of neurogenesis, the researchers hunted for specific proteins produced by neurons at particular stages of development. Proteins such as GFAP and SOX2, for example, are made in abundance by stem cells that eventually turn into neurons, while newborn neurons make more of proteins such as Ki-67. In all of the brains, the researchers found evidence of newborn neurons in the dentate gyrus, the part of the hippocampus where neurons are born.

Although the number of neural stem cells was a bit lower in people in their 70s compared with people in their 20s, the older brains still had thousands of these cells. The number of young neurons in intermediate to advanced stages of development was the same across people of all ages.

Still, the healthy older brains did show some signs of decline. Researchers found less evidence for the formation of new blood vessels and fewer protein markers that signal neuroplasticity, or the brain’s ability to make new connections between neurons. But it’s too soon to say what these findings mean for brain function, Boldrini says. Studies on autopsied brains can look at structure but not activity.

Not all neuroscientists are convinced by the findings. “We don’t think that what they are identifying as young neurons actually are,” says Arturo Alvarez-Buylla of the University of California, San Francisco, who coauthored the recent paper that found no signs of neurogenesis in adult brains. In his study, some of the cells his team initially flagged as young neurons turned out to be mature cells upon further investigation.

But others say the new findings are sound. “They use very sophisticated methodology,” Frisén says, and control for factors that Alvarez-Buylla’s study didn’t, such as the type of preservative used on the brains.

via Human brains make new nerve cells — and lots of them — well into old age | Science News

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[Review] Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease – Full Text

Abstract

Introduction

Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic reality in post-stroke rehabilitation. It has a neuroprotective effect on the modulation of neuroplasticity, improving the brain’s capacity to retrain neural circuits and promoting restoration and acquisition of new compensatory skills.

Development

We conducted a literature search on PubMed and also gathered the latest books, clinical practice guidelines, and recommendations published by the most prominent scientific societies concerning the therapeutic use of rTMS in the rehabilitation of stroke patients. The criteria of the International Federation of Clinical Neurophysiology (2014) were followed regarding the inclusion of all evidence and recommendations.

Conclusions

Identifying stroke patients who are eligible for rTMS is essential to accelerate their recovery. rTMS has proven to be safe and effective for treating stroke complications. Functional brain activity can be optimised by applying excitatory or inhibitory electromagnetic pulses to the hemisphere ipsilateral or contralateral to the lesion, respectively, as well as at the level of the transcallosal pathway to regulate interhemispheric communication. Different studies of rTMS in these patients have resulted in improvements in motor disorders, aphasia, dysarthria, oropharyngeal dysphagia, depression, and perceptual-cognitive deficits. However, further well-designed randomised controlled clinical trials with larger sample size are needed to recommend with a higher level of evidence, proper implementation of rTMS use in stroke subjects on a widespread basis.

Introduction

Stroke patients should receive early neurorehabilitation after convalescence. For many years, researchers have aimed to identify new therapeutic targets to hasten recovery from stroke. However, we continue to lack a universally accepted, approved pharmacological therapy for these patients.1234 ;  5 After stroke, organisational changes in brain interneuronal activity in the affected area and the surrounding healthy tissue may on occasion promote functional recovery. Neurorehabilitation may help achieve this aim. Unfortunately, there are also occasions when neural reorganisation is suboptimal; in these cases, the problem persists and becomes chronic. In this context, transcranial magnetic stimulation (TMS) emerged as a tool for studying the brain and has been used since the mid-1980s to treat certain neuropsychiatric disorders. Neurorehabilitation is based on the idea that the brain is a dynamic entity able to adapt to internal and external homeostatic changes. This adaptive capacity, called neuroplasticity, is also present in patients with acquired brain injuries. The degree of recovery and the functional prognosis of these patients depend on the extent of neuroplastic changes.12345 ;  6 When performed by experienced physicians, TMS is a safe, non-invasive technique which enables the organisation of these neural changes (Fig. 1). The technique’s applications are expanding rapidly.12345678 ;  9

Modern TMS device.

Figure 1.

Modern TMS device.

We present the results of a literature review of the most relevant articles, manuals, and clinical practice guidelines addressing TMS (background information, diagnostic and therapeutic uses, and especially its usefulness for stroke neurorehabilitation) and published between 1985 (when the technique was first used) and 2015.

 

Development

The organisation of language in the brain

The left hemisphere of the brain is the anatomo-functional seat of language in 96% of right-handed and 70% of left-handed individuals. Language processing in the left hemisphere involves certain anatomical pathways for language comprehension, repetition, and production (Fig. 2). Positron emission tomography and functional magnetic resonance imaging (fMRI) studies conducted during multiple language tasks have shown brain activation not only in the main language centres (lesions to these areas may cause Broca aphasia, Wernicke aphasia, etc.) (Fig. 3) but also in many other locations, such as the thalamus (alertness), the basal ganglia (motor modulation), and the limbic system (affect and memory). Language is the perfect model for understanding how the central nervous system works as a whole.10 ;  11

Figure 2. The functional pathways involved in comprehension, repetition, and production of written, gesture, and spoken language, according to the Wernicke-Geschwind model. Within the left hemisphere, language organisation follows certain anatomical pathways for language comprehension, repetition, and production. Sounds are processed by the bilateral auditory cortex, in the superior temporal gyrus (primary auditory area), and decoded in the posterior area of the left temporal cortex (Wernicke area); the latter is connected to other cortical areas or networks which assign meaning to words. During reading, output from the primary visual area (bilaterally) travels to other parieto-occipital association areas for word and phrase recognition (especially the left fusiform gyrus, located in the inferior surface of the temporal lobe, where there is a key word recognition centre) and reaches the angular gyrus, which processes language-related visual and auditory information. In spontaneous language repetition and production, auditory information must travel through the arcuate fasciculus towards the left inferior frontal region (Broca area), which is responsible for language production; this area is also known to be involved in such other functions as action comprehension (mirror neurons). To produce written or spoken language, output from the Wernicke area, the Broca area, and nearby association areas must reach the primary motor cortex.10 ;  11
Adapted with permission from Bear et al.10

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Continue —> Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease

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[ARTICLE] Cerebral Reorganization in Subacute Stroke Survivors after Virtual Reality-Based Training: A Preliminary Study – Full Text

Abstract

Background

Functional magnetic resonance imaging (fMRI) is a promising method for quantifying brain recovery and investigating the intervention-induced changes in corticomotor excitability after stroke. This study aimed to evaluate cortical reorganization subsequent to virtual reality-enhanced treadmill (VRET) training in subacute stroke survivors.

Methods

Eight participants with ischemic stroke underwent VRET for 5 sections per week and for 3 weeks. fMRI was conducted to quantify the activity of selected brain regions when the subject performed ankle dorsiflexion. Gait speed and clinical scales were also measured before and after intervention.

Results

Increased activation in the primary sensorimotor cortex of the lesioned hemisphere and supplementary motor areas of both sides for the paretic foot (p < 0.01) was observed postintervention. Statistically significant improvements were observed in gait velocity (p < 0.05). The change in voxel counts in the primary sensorimotor cortex of the lesioned hemisphere is significantly correlated with improvement of 10 m walk time after VRET (r = −0.719).

Conclusions

We observed improved walking and increased activation in cortical regions of stroke survivors after VRET training. Moreover, the cortical recruitment was associated with better walking function. Our study suggests that cortical networks could be a site of plasticity, and their recruitment may be one mechanism of training-induced recovery of gait function in stroke. This trial is registered with ChiCTR-IOC-15006064.

1. Introduction

Gait impairment is a common consequence of stroke, and the decreases in gait velocity, stride length, and cadence are hallmark features of gait pattern alterations in stroke survivors [12]. Previous studies found that early intervention with physical therapy and gait training to restore walking after stroke was recommended to improve motor function and decrease disability [34]. As gait impairments are a result of deficient neuromuscular control, a better understanding of the impact and mechanism of those interventions on gait pattern recovery after stroke is therefore essential.

Environmental factors act as critical determinants for the level of community ambulation of stroke patient [5]. The development of computers has resulted in virtual reality (VR) tools which can create life-like scenarios via visual, auditory, and tactile feedback and can provide subjects with a safe and stimulating learning environment [6]. VR has been increasingly used in poststroke rehabilitation; therapy interventions using VR may improve motor function for those patients [715]. VR system might represent the main neural substrate for relearning or resuming impaired motor functions following stroke. A key challenge in neurorehabilitation is to establish optimal training protocols for the given patient [10]. VR could provide a person with senses of encouragement and accomplishment [1619]. However, two main concerns need to be investigated. What kind of rehabilitation strategies can combine with VR, and what degree for those VR combined rehabilitation strategies can facilitate stroke patients? Recently, motor relearning strategies can be applied in VR-enhanced treadmill (VRET) training by numerous movement repetitions and a multisensory approach to stimulate brain plasticity and patients receive visual feedback which is close to real-life experience [12]. While the positive benefits of VRET exercise on gait speed, cadence, step length, community walking time, and balance have been demonstrated [7911121415], the associated changes of brain activity with this training have not been investigated yet.

Advances in imaging, such as blood oxygenation level-dependent functional magnetic resonance imaging (fMRI), have been allowed for the observation of changes in cerebral plasticity and the exploration of recovery mechanisms. The control of gait involves the planning and execution from multiple cortical areas, such as secondary and premotor cortex [11]. Ankle dorsiflexion is an important kinematic aspect of the gait cycle. Using ankle movement, Enzinger et al. [20] observed increased activation in the unlesioned hemisphere associated with increasing functional impairment of the paretic leg in patients with stroke. fMRI studies of patients after stroke have suggested that VR could increase neural activations in the primary motor areas and improve lateralization of primary sensorimotor cortex (SMC) activity [2123]. We hypothesized that recovery of lower limb function after VRET would be associated with changes in brain activation during ankle dorsiflexion.

Therefore, the primary aim of this preliminary study was to investigate if functional reorganization takes place after VRET in subacute stroke survivors with gait impairment, using fMRI and an ankle dorsiflexion paradigm. Correlation between clinical scale changes after VERT and brain activation alterations was also studied to see the relations of the induction of cortical plasticity and functional recovery in subacute stroke survivors. We hope that the results of the current study could help to understand the mechanism of VRET as an early intervention for gait recovery for stroke.

2. Methods

2.1. Participants

Eight stroke survivors were recruited in this study, aged 41–72 years (mean: 58.38 years) and included 6 males and 2 females (Table 1 and Figure 1). Inclusion criteria: (i) 18 to 80 years in ages; (ii) right-foot dominant; (iii) first incident of ischemic cortical or subcortical stroke which resulted in gait impairment; (iv) stroke was confirmed by MRI within the past 3 months of inclusion; (v) at least 10° of dorsiflexion is available at the ankle. Exclusion criteria: (i) contraindication to MRI scan (implanted medical devices incompatible with MRI testing or claustrophobia); (ii) history of stroke resulted in function impairment; (iii) history of mental disorder or the use of antipsychotic medication; (iv) cognitive impairment (Mini-Mental State Examination score of less than 24 points); (v) unable to speak or hear; (vi) history of recent deep vein thrombosis of the lower limbs; (vii) recent myocardial infarction; (viii) medically unstable; (ix) existing lower extremity pathology. This study was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University (SYSU), and all subjects provided informed consent before the experiments.

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Figure 1
Axial structural T1-weighted MRI scans at the level of maximum infarct volume for each patient. And right hemisphere patients flipped on the sagittal axis for better comparison.

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[WEB SITE] DARPA Is Planning to Hack the Human Brain to Let Us “Upload” Skills

IN BRIEF

The DARPA Targeted Neuroplasticity Training (TNT) program is exploring ways to speed up skill acquisition by activating synaptic plasticity. If the program succeeds, downloadable learning that happens in a flash may be the result.

MINDHACK FOR FASTER LEARNING

In March 2016, DARPA — the U.S. military’s “mad science” branch — announced their Targeted Neuroplasticity Training(TNT) program. The TNT program aims to explore various safe neurostimulation methods for activating synaptic plasticity, which is the brain’s ability to alter the connecting points between neurons — a requirement for learning. DARPA hopes that building up that ability by subjecting the nervous system to a kind of workout regimen will enable the brain to learn more quickly.

[Taken]Military Researchers Are Hacking the Human Brain So We Can Learn Much Faster
Credit: DARPA

The ideal end benefit for this kind of breakthrough would be downloadable learning. Rather than needing to learn, for example, a new language through rigorous study and practice over a long period of time, we could basically “download” the knowledge after putting our minds into a highly receptive, neuroplastic state. Clearly, this kind of research would benefit anyone, but urgent military missions can succeed or fail based on the timing. In those situations, a faster way to train personnel would be a tremendous boon.

FIRST NEUROSTIMULATION, THEN APPLICATION

As part of the TNT program, DARPA is funding eight projects at seven institutions. All projects are part of a coordinated effort that will first study the fundamental science undergirding brain plasticity and will conclude with human trials. The first portion of the TNT program will work to unravel the neural mechanisms that allow nerve stimulation to influence brain plasticity. The second portion of the program will practically apply what has been learned in a variety of training exercises.

To ensure the work stays practical, foreign language specialists, intelligence analysts, and others who train personnel now will work with researchers to help refine the TNT platform to suit military training needs. Researchers will compare the efficacy of using an implanted device to stimulate the brain versus non-invasive stimulation. They will also explore both the ethics of enhanced learning through neurostimulation and ways to avoid side effects and potential risks.

The Evolution of Brain-Computer Interfaces [INFOGRAPHIC]
Click to View Full Infographic

“The Defense Department operates in a complex, interconnected world in which human skills such as communication and analysis are vital, and the Department has long pushed the frontiers of training to maximize those skills,” Doug Weber, the TNT Program Manager, said in a DARPA press release. “DARPA’s goal with TNT is to further enhance the most effective existing training methods so the men and women of our Armed Forces can operate at their full potential.”

If the TNT program succeeds, striving to be all you can be may mean learning at a much faster pace, and not just for military personnel. Downloadable learning may be one of the ways we achieve next-level humanity.

 

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[BLOG POST] Where does the controversial finding that adult human brains don’t grow new neurons leave ongoing research?

Scientists have known for about two decades that some neurons – the fundamental cells in the brain that transmit signals – are generated throughout life. But now a controversial new study from the University of California, San Francisco, casts doubt on whether many neurons are added to the human brain after birth.

As a translational neuroscientist, this work immediately piqued my interest. It has direct implications for the research my lab does: We transplant young neurons into damaged brain areas in mice in an attempt to treat epileptic seizures and the damage they’ve caused. Like many labs, part of our work is based on a foundational belief that the hippocampus is a brain region where new neurons are born throughout life.

If the new study is right, and human brains for the most part don’t add new neurons after infancy, researchers like me need to reconsider the validity of the animal models we use to understand various brain conditions – in my case temporal lobe epilepsy. And I suspect other labs that focus on conditions including drug addiction, depression and post-traumatic stress disorder are thinking about what the UCSF study means for their investigations, too.

In the brain of a baby who died soon after birth, there are many new neurons (green in this image) in the hippocampus. Sorrells et alCC BY-ND

When and where are new neurons born?

No doubt, the adult human brain is able to learn throughout life and to change and adapt – a capability brain scientists call neuroplasticity, the brain’s ability to reorganize itself by rewiring connections. Yet, a central dogma in the field of neuroscience for nearly 100 years had been that a child is born with all the neurons she will ever have because the adult brain cannot regenerate neurons.

Just over half a century ago, researchers devised a way to study proliferation of cells in the mature brain, based on techniques to incorporate a radioactive label into new cells as they divide. This approach led to the startling discovery in the 1960s that rodent brains actually could generate new neurons.

Neurogenesis – the production of new neurons – was previously thought to only occur during embryonic life, a time of extremely rapid brain growth and expansion, and the rodent findings were met with considerable skepticism. Then researchers discovered that new neurons are also born throughout life in the songbird brain, a species scientists use as a model for studying vocal learning. It started to look like neurogenesis plays a key role in learning and neuroplasticity – at least in some brain regions in a few animal species.

Even so, neuroscientists were skeptical that many nerve cells could be renewed in the adult brain; evidence was scant that dividing cells in mammalian brains produced new neurons, as opposed to other cell types. It wasn’t until researchers extracted neural stem cells from adult mouse brains and grew them in cell culture that scientists showed these precursor cells could divide and differentiate into new neurons. Now it is generally well accepted that neurogenesis takes place in two areas of the adult rodent brain: the olfactory bulbs, which process smell information, and the hippocampus, a region characterized by neuroplasticity that is required for forming new declarative memories.

Adult neural stem cells cluster together in what scientists call niches – hotbeds for cultivating the birth and growth of new neurons, recognizable by their distinctive architecture. Despite the mounting evidence for regional growth of new neurons, these studies underscored the point that the adult brain harbors only a few stem cell niches and their capacity to produce neurons is limited to just a few types of cells.

With this knowledge, and new tools for labeling proliferating cells and identifying maturing neurons, scientists began to look for postnatal neurogenesis in primate and human brains.

What’s happening in adult human brains?

Many neuroscientists believe that by understanding the process of adult neurogenesis we’ll gain insights into the causes of some human neurological disorders. Then the next logical step would be trying to develop new treatments harnessing neurogenesis for conditions such as Alzheimer’s disease or trauma-induced epilepsy. And stimulating resident stem cells in the brain to generate new neurons is an exciting prospect for treating neurodegenerative diseases.

Because neurogenesis and learning in rodents increases with voluntary exercise and decreases with age and early life stress, some workers in the field became convinced that older people might be able to enhance their memory as they age by maintaining a program of regular aerobic exercise.

However, obtaining rigorous proof for adult neurogenesis in the human and primate brain has been technically challenging – both due to the limited experimental approaches and the larger sizes of the brains, compared to reptiles, songbirds and rodents.

Researchers injected a compound found in DNA, nicknamed BrdU to identify brand new neurons in human adult hippocampus – but the labeled cells were extremely rare. Other groups demonstrated that adult human brain tissue obtained during neurosurgery contained stem cell niches that housed progenitor cells that could generate new neurons in the lab, showing that these cells had an inborn neurogenic capacity, even in adults.

But even when scientists saw evidence for new neurons in the brain, they tended to be scarce. Some neurogenesis experts were skeptical that evidence based on incorporating BrdU into DNA was a reliable method for proving that new cells were actually being born through cell division, rather than just serving as a marker for other normal cell functions.

Further questions about how long human brains retain the capacity for neurogenesis arose in 2011, with a study that compared numbers of newborn neurons migrating in the olfactory bulbs of infants versus older individuals up to 84 years of age. Strikingly, in the first six months of life, the baby brains contained lots of chains of young neurons migrating into the frontal lobes, regions that guide executive function, long-range planning and social interactions. These areas of the human cortex are hugely increased in size and complexity compared to rodents and other species. But between 6 to 18 months of age, the migrating chains dwindled to a thin stream. Then, a very different pattern emerged: Where the migrating chains of neurons had been in the infant brain, a cell-free gap appeared, suggesting that neural stem cells become depleted during the first six months of life.

Questions still lingered about the human hippocampus and adult neurogenesis as a source for its neuroplasticity. One group came up with a clever approach based on radiocarbon dating. They measured how much atmospheric ¹⁴C – a radioactive isotope derived from nuclear bomb tests – was incorporated into people’s DNA. This method suggested that as many as 700 new cells are added to the adult human hippocampus every day. But these findings were contradicted by a 2016 study that found that the neurogenic cells in the adult hippocampus could only produce non-neuronal brain cells called microglia.

Rethinking neurogenesis research

Now the largest and most comprehensive study conducted to date presents even stronger evidence that robust neurogenesis doesn’t continue throughout adulthood in the human hippocampus – or if it does persist, it is extremely rare. This work is controversial and not universally accepted. Critics have been quick to cast doubt on the results, but the finding isn’t totally out of the blue.

So where does this leave the field of neuroscience? If the UCSF scientists are correct, what does that mean for ongoing research in labs around the world?

Because lots of studies of neurological diseases are done in mice and rats, many scientists are invested in the possibility that adult neurogenesis persists in the human brain, just as it does in rodents. If it doesn’t, how valid is it to think that the mechanisms of learning and neuroplasticity in our model animals are comparable to those in the human brain? How relevant are our models of neurological disorders for understanding how changes in the hippocampus contribute to disorders such as the type of epilepsy I study?

In my lab, we transplant embryonic mouse or human neurons into the adult hippocampus in mice, after damage caused by epileptic seizures. We aim to repair this damage and suppress seizures by seeding the mouse hippocampus with neural stem cells that will mature and form new connections. In temporal lobe epilepsy, studies in adult rodents suggest that naturally occurring hippocampal neurogenesis is problematic. It seems that the newborn hippocampal neurons become highly excitable and contribute to seizures. We’re trying to inhibit these newborn hyperexcitable neurons with the transplants. But if humans don’t generate new hippocampal neurons, then maybe we’re developing a treatment in mice for a problem that has a different mechanism in people.

Perhaps our species has evolved separate mechanisms for neuroplasticity, distinct from those used by species such as rats and mice. One possibility is that there are other sites in the human brain where neurogenesis occurs – its a big structure and more exploration will be necessary. If it turns out to be true that the human brain has a diminished capacity for neurogenesis after birth, the finding will have important implications for how neuroscientists like me think about tackling brain disorders.

Perhaps most importantly, this work underscores how crucial it is to learn how to increase the longevity of the neurons we do have, born early in life, and how we might replace or repair neurons that become damaged.

via Where does the controversial finding that adult human brains don’t grow new neurons leave ongoing research?

 

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[TED] 3 Clues to undertand your Brain – TED Talks

Vilayanur Ramachandran tells us what brain damage can reveal about the connection between celebral tissue and the mind, using three startling delusions as examples.

Neurologist V.S. Ramachandran looks deep into the brain’s most basic mechanisms. By working with those who have very specific mental disabilities caused by brain injury or stroke, he can map functions of the mind to physical structures of the brain.

 

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[ARTICLE] Neuroplasticity of cognitive control networks following cognitive training for chronic traumatic brain injury – Full Text

Abstract

Cognitive control is the ability to coordinate thoughts and actions to achieve goals. Cognitive control impairments are one of the most persistent and devastating sequalae of traumatic brain injuries (TBI). There have been efforts to improve cognitive control in individuals with post-acute TBI. Several studies have reported changes in neuropsychological measures suggesting the efficacy of cognitive training in improving cognitive control. Yet, the neural substrates of improved cognitive control after training remains poorly understood. In the current study, we identified neural plasticity induced by cognitive control training for TBI using resting-state functional connectivity (rsFC). Fifty-six individuals with chronic mild TBI (9 years post-injury on average) were randomized into either a strategy-based cognitive training group (N = 26) or a knowledge-based training group (active control condition; N = 30) for 8 weeks. We acquired a total of 109 resting-state functional magnetic resonance imaging from 45 individuals before training, immediately post-training, and 3 months post-training. Relative to the controls, the strategy-based cognitive training group showed monotonic increases in connectivity in two cognitive control networks (i.e., cingulo-opercular and fronto-parietal networks) across time points in multiple brain regions (pvoxel < 0.001, pcluster < 0.05). Analyses of brain-behavior relationships revealed that fronto-parietal network connectivity over three time points within the strategy-based cognitive training group was positively associated with the trail making scores (pvoxel < 0.001, pcluster < 0.05). These findings suggest that training-induced neuroplasticity continues through chronic phases of TBI and that rsFC can serve as a neuroimaging biomarker of evaluating the efficacy of cognitive training for TBI.

1. Introduction

A traumatic brain injury (TBI) occurs when external force is applied to the head leading to disruptions of brain structure and function (Faul et al., 2010). Though an insult to the brain occurs instantaneously, a TBI incident can be the beginning of a chronic disease process rather than an isolated event or final outcome across all levels of initial injury severity: moderate or severe TBI (Corrigan et al., 2014Masel and DeWitt, 2010Whitnall et al., 2006) and mild-to-severe TBI (Masel and DeWitt, 2010Whitnall et al., 2006). For example, TBI can be a risk factor for cognitive impairments (Arciniegas et al., 2002Rabinowitz and Levin, 2014), psychiatric disorders (Hesdorffer et al., 2009), reduced social functioning (Temkin et al., 2009), and neurodegenerative diseases such as chronic traumatic encephalopathy (McKee et al., 2013). A substantial number of individuals with TBI sustain TBI-related disabilities. For example, 57% of individuals 16 years or older with moderate or severe TBI were moderately or severely disabled, and 39% had a worse global outcome at 5 years post-injury compared to their outcome level at 1 or 2 years post-injury (Corrigan et al., 2014). Currently, as many as 5.3 million people in the U.S. are facing challenges of TBI-related disability (Frieden et al., 2015). The actual number of individuals continuing to suffer from chronic TBI (>6 months post-injury time) effects may be greater than the estimates given the lack of public awareness of TBI in the past and the limited sensitivity of conventional neuropsychological measures (Katz and Alexander, 1994). Additionally, conventional clinical imaging (e.g., CT scanning) may be insensitive to identifying brain abnormalities especially in individuals with mild TBI (Tellier et al., 2009). Substantial numbers of individuals with sustained TBI necessitates further rehabilitation research in chronic TBI (Katz and Alexander, 1994).

Resting-state functional connectivity (rsFC) is a technique measuring the temporal coherence of blood oxygenation level dependent (BOLD) signal from anatomically separated brain regions acquired at rest. Since its inception (Biswal et al., 1995), rsFC in resting-state functional magnetic imaging (rsfMRI) has provided new insights about brain networks that can better explain the underlying mechanisms of human behavior or function (van den Heuvel and Hulshoff Pol, 2010). RsFC studies in clinical populations are increasingly popular because they do not require that subjects perform a specific task. RsFC is well-positioned to identify both the patterns of injury and the associations between injury and behavioral impairments in TBI (Sharp et al., 2014). This is especially important as diffuse axonal injury (DAI) is one of the primary injury mechanisms of TBI (Smith et al., 2003). DAI induces multi-focal injuries to axons which provide the structural basis of spatially distributed brain networks. Thus, DAI leads to a breakdown of brain network connectivity. In the context of rehabilitation, rsFC is also a promising technique to measure neuroplasticity within the injured brain, as rsFC has been successfully utilized to provide evidence for experience-induced neuroplasticity of the adult human brain in vivo ( Guerra-Carrillo et al., 2014Kelly and Castellanos, 2014). For example, in healthy subjects, previous studies reported changes in rsFC after motor training (Lewis et al., 2009Taubert et al., 2011), cognitive training (Jolles et al., 2013Mackey et al., 2013Takeuchi et al., 2013), and physical activity in older adults (Voss et al., 2010). In clinical populations, changes in rsFC after cognitive rehabilitation for cognitive symptoms associated with multiple sclerosis has been reported (de Giglio et al., 2016Keshavan et al., 2017). This technique is well-suited to investigating neuroplasticity induced by rehabilitation for TBI.

In a previous study, we reported the efficacy of strategy-based cognitive training for chronic TBI, utilizing neuropsychological measures (Vas et al., 2016). This training is an integrative program to improve cognitive control by exerting more efficient thinking strategies for selective attention and abstract reasoning (see the Materials and methods section for the details of training protocols). Cognitive control (also called executive function) is the ability to coordinate thoughts and actions to achieve goals while adjusting these goals according to changing environments (Nomura et al., 2010). Cognitive control is critical to successfully perform daily life tasks (Botvinick et al., 2001Diamond, 2013). Thus, impairment in cognitive control is one of the most persistent and devastating sequalae of TBI (Cicerone et al., 2000Rabinowitz and Levin, 2014), and empirical studies demonstrating the efficacy of cognitive rehabilitation for improving cognitive control of individuals with post-acute TBI are valuable in the literature on TBI rehabilitation (Cicerone et al., 2006McDonald et al., 2002). In the current study, we describe rehabilitation-induced changes in brain connectivity.

Cognitive control has been extensively investigated in the field of cognitive neuroscience (Power and Petersen, 2013). Of note, Dosenbach and colleagues (Dosenbach et al., 2006) identified a set of regions that are active across multiple cognitive control tasks. A follow-up study (Dosenbach et al., 2007) revealed two distinct resting-state networks related to cognitive control: the cingulo-opercular network and fronto-parietal network. The cingulo-opercular network consists of bilateral anterior insula/frontal opercula (aI/fO), bilateral anterior prefrontal cortices (aPFC), dorsal anterior cingulate cortex (dACC), and thalamus, and it is thought to support stable maintenance of task mode and strategy during cognitive processes (Dosenbach et al., 2007 ;  Dosenbach et al., 2008). The fronto-parietal network comprises of bilateral dorsolateral prefrontal cortices (dlPFC), bilateral dorsal frontal cortices (dFC), bilateral inferior parietal lobules (IPL), bilateral intraparietal sulci (IPS), middle cingulate cortex (mCC), and bilateral precunei (PCUN), supporting active, adaptive online control during cognitive control processes (Dosenbach et al., 2007 ;  Dosenbach et al., 2008). The cingulo-opercular network and fronto-parietal network are also referred to as the salience network and central executive network, respectively (Seeley et al., 2007). The salience and central executive networks are often referred to in the context of interactions among these networks and the default mode network (Menon and Uddin, 2010). However, in this report, we will refer to them as the cingulo-opercular and fronto-parietal networks, as we conducted current study in the context of cognitive control. TBI-induced disruptions to the cingulo-opercular in mild-to-severe TBI (Bonnelle et al., 2012Jilka et al., 2014Stevens et al., 2012) and fronto-parietal networks in mild TBI (Mayer et al., 2011Stevens et al., 2012) have been previously reported. Specifically, TBI decreases the white matter integrity of the cingulo-opercular network (Bonnelle et al., 2012) and functional connectivity between the cingulo-opercular and default networks during a cognitive control task (Jilka et al., 2014). Additionally, individuals with mild TBI showed increases and decreases in rsFC with the cingulo-opercular (Stevens et al., 2012) and fronto-parietal networks (Mayer et al., 2011Stevens et al., 2012) across brain regions, relative to healthy individuals.

We utilized rsfMRI to identify the effects of a strategy-based cognitive training for chronic TBI on the cognitive control networks (i.e., cingulo-opercular and fronto-parietal networks) compared to a knowledge-based comparison condition. We focused on the cingulo-opercular and fronto-parietal networks as our training protocols were aimed at improving cognitive control processes (See the Materials and methods section for the details of training protocols). We randomized individuals with chronic mild TBI into two eight-week training groups (strategy- versus knowledge-based), and we acquired their MRI scans over three time points (prior to training, after training, and at three-months follow-up after training completed). We then investigated the spatial and temporal patterns of training-induced changes in cingulo-opercular and fronto-parietal networks connectivity of these individuals. We hypothesized that strategy-based cognitive training would induce changes in the cingulo-opercular and fronto-parietal networks connectivity relative to the knowledge-based training program. This prediction is based on findings from previous rsfMRI studies demonstrating neuroplasticity in healthy adults and other clinical populations (de Giglio et al., 2016Jolles et al., 2013Keshavan et al., 2017Lewis et al., 2009Mackey et al., 2013Takeuchi et al., 2013Taubert et al., 2011Voss et al., 2010) and the efficacy of strategy-based cognitive training for chronic TBI (Vas et al., 2016).[…]

 

Continue —> Neuroplasticity of cognitive control networks following cognitive training for chronic traumatic brain injury

 

Fig. 1

Fig. 1. Seed locations. Black and yellow circles represent seeds for the cingulo-opercular network and fronto-parietal network, respectively. aI/fO, anterior insula/frontal operculum; aPFC, anterior prefrontal cortex; dACC, dorsal anterior cingulate cortex; dFC, dorsal frontal cortex; dlPFC, dorsolateral prefrontal cortex; IPS; intraparietal sulcus; mCC, middle cingulate cortex; PCUN, precuneus; L, left; R, right.

 

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[Abstract+References] Evidence for Training-Dependent Structural Neuroplasticity in Brain-Injured Patients: A Critical Review

Acquired brain injury (ABI) is associated with a range of cognitive and motor deficits, and poses a significant personal, societal, and economic burden. Rehabilitation programs are available that target motor skills or cognitive functioning. In this review, we summarize the existing evidence that training may enhance structural neuroplasticity in patients with ABI, as assessed using structural magnetic resonance imaging (MRI)–based techniques that probe microstructure or morphology. Twenty-five research articles met key inclusion criteria. Most trials measured relevant outcomes and had treatment benefits that would justify the risk of potential harm. The rehabilitation program included a variety of task-oriented movement exercises (such as facilitation therapy, postural control training), neurorehabilitation techniques (such as constraint-induced movement therapy) or computer-assisted training programs (eg, Cogmed program). The reviewed studies describe regional alterations in white matter architecture and/or gray matter volume with training. Only weak-to-moderate correlations were observed between improved behavioral function and structural changes. While structural MRI is a powerful tool for detection of longitudinal structural changes, specific measures about the underlying biological mechanisms are lacking. Continued work in this field may potentially see structural MRI metrics used as biomarkers to help guide treatment at the individual patient level.

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via Evidence for Training-Dependent Structural Neuroplasticity in Brain-Injured Patients: A Critical Review – Karen Caeyenberghs, Adam Clemente, Phoebe Imms, Gary Egan, Darren R. Hocking, Alexander Leemans, Claudia Metzler-Baddeley, Derek K. Jones, Peter H. Wilson, 2018

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[Review] Transcranial Electrical Brain Stimulation – Full Text

Abstract

Transcranial electrical brain stimulation using weak direct current (tDCS) or alternating current (tACS) is being increasingly used in clinical and experimental settings to improve cognitive and motor functions in healthy subjects as well as neurological patients. This review focuses on the therapeutic value of transcranial direct current stimulation for neurorehabilitation and provides an overview of studies addressing motor and non-motor symptoms after stroke, disorders of attention and consciousness as well as Parkinson’s disease.

 

Background

The past 10 years have seen an increased clinical and experimental focus on noninvasive electrical brain stimulation as an innovative therapeutic approach to support neurorehabilitation. This entails the application of either transcranial direct current stimulation (tDCS), or less commonly, transcranial alternating current stimulation (tACS). Typically, up to 0.8 A/m² is used for up to 40 min per single stimulation session [1]. The electrical current partially penetrates the underlying structures and affects nerve cells, glia and vessels in the stimulated brain area [1] [2]. Early animal experiments during the 1960s and 1970s on the effects of weak DC stimulation demonstrated an excitement-induced change of neurons lasting several hours after the end of the stimulation [3] [4]. Therapeutic studies of the 1970s, at that time mainly concerning the treatment of depression, did not yield any success, which in retrospect could be attributed to the stimulation parameters used. In 2 000 key experiments by Nitsche and Paulus on polarity-related excitability changes in the human motor system after transcranial application of tDCS led to a renewed interest in the approach [5]. The authors documented increased cortical excitability measured by the amplitude of motor-evoked potentials in healthy volunteers after anodal stimulation above the motor cortex lasting at least 9 min [6]. Reversing the direction of stimulation (cathodal tDCS) resulted in a decrease in motor-evoked potential. In addition to the concept of pure excitability modulation, a large number of studies demonstrate modulation of neuroplasticity by tDCS in various ways, including basic scientific and mechanistic findings regarding improvement of synaptic transmission strength [7] [8] [9], long-term influence on learning processes and behavior [10] [11], as well as a therapeutic approach to improve function in neurological and psychiatric disorders associated with altered or disturbed neuroplasticity (overview in [12]). In particular, simultaneous application of tDCS together with different learning paradigms, such as motor or cognitive training, appears to produce favorable effects in healthy subjects and in various patient groups [11] [13].

The following review presents the effects of tDCS on the improvement in the function of some neurological disease patterns which are regularly the focus of neurorehabilitative treatment. This especially includes stroke. In addition, we shall refer to a current database of clinical studies containing a comprehensive list of scientific and clinical studies of tDCS in the treatment of neurological and psychiatric disorders [14].

Post-stroke Motor Impairment

Stroke is one of the primary causes worldwide of permanent limitations of motor function and speech. Despite intensive rehabilitation efforts, approx. 50% of stroke patients remain limited in their motor and speech capabilities [15] [16] [17]. Current understanding of the mechanisms of tDCS is largely based on data documented for the human motor system. The reasons for this include the presence of direct and easily objectifiable measurement criteria (for example, motor-evoked potential, fine motor function), as well as anatomical accessibility of brain motor regions for non-invasive stimulation. Therefore, it is not surprising that the clinical syndrome of stroke with the frequent symptom of hemiparesis as a “lesion model of the pyramidal tract” received significant scientific interest with respect to researching the effects of tDCS, as evidenced by the numerous scientific publications since 2005 ([Fig. 1]). In contrast to earlier largely mechanistic studies, in the past 5 years there has been a trend toward studies addressing clinically-oriented therapeutic issues. […]

Continue —> Thieme E-Journals – Neurology International Open / Full Text

Fig. 2 Illustration of the 3 typical brain stimulation montages exemplified by tDCS above the motor cortex. In example a, the anode (red) is placed above the ipsilesional motor cortex, and the cathode (blue) is located on the contralateral forehead. Example b shows the cathode placed above the motor cortex of the non-lesioned hemisphere, and the anode is placed on the contralateral forehead. Example c illustrates bihemispheric montage, with the anode located above the ipsilesional motor cortex, and the cathode placed above the motor cortex of the non-lesioned hemisphere. The white arrow shows the intracerebral current flow. The goal of these 3 arrangements is to modulate the interaction between both motor cortices by changing the activity of one or both hemispheres c.

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[Editorial] Improving and Predicting Outcomes of Traumatic Brain Injury: Neuroplasticity, Imaging Modalities, and Perspective Therapy – Neural Plasticity

Each year, a new traumatic brain injury (TBI) event occurs in
an estimated 10 million people worldwide, particularly in
young adults. Not only is TBI the leading cause of longterm
disability and mortality worldwide, but it is also
expected to become the third largest cause of global disease
burden by 2020 [1, 2]. TBI is a challenging disease process,
both to treat and to investigate. TBI survivors often experience
substantial and lifelong cognitive, physical, and behavioral
impairments that require long-term access to health
care and disability services.
Over the past three decades, imaging modalities, such as
positron emission tomography (PET),functionalMRI (fMRI),
diffusion tensor imaging (DTI), and transcranial magnetic
stimulation (TMS), have played a pivotal role in predicting
TBI outcome and advancing TBI treatment [3].
Burgeoning evidences for neuroplasticity have shed light
on the potential therapeutic protocols focusing on synaptic
proteins, new network connections, inflammatory reactions,
and the recruitment of immune cells [4]. Future therapies,
including gene therapies or a combination of different pharmacologic
therapies and rehabilitative protocols, which may
benefit victims by targeting multiple mechanisms of recovery,
are of utmost interest and currently under heavy investigation
by devoting neuroscientists.
The articles contained in this special issue include 4
reviews and 2 original research papers: a quantitative study
focusing on predictors of recovery from TBI and a cohort
study on substance related disorder after TBI.

(i) TBI survivors suffer various functional and cognitive
sequelae that may impose serious medical and social
problems. J. Ma et al. reviewed the complicated
pathological mechanisms of diffuse axonal injury
(DAI) in an attempt to facilitate more accurate diagnosis
and hence improve the survival and life quality
of DAI patients.

(ii) Not many studies have discussed the role of synapses
after TBI. Z. Wen et al. provided a comprehensive
review on the role and mechanisms of synapses in
TBI and the correlation between key synaptic proteins
and neuroplasticity. The article also provides
insights on the role of synapses in the treatment
and prognosis of TBI.

(iii) Molecular studies concerning the microglia-induced
inflammation by M1 phenotype and antiinflammation
by M2 phenotype are a new strategy
for treatment of TBI. In the paper titled “The

Polarization States of Microglia in TBI: A New
Paradigm for Pharmacological Intervention,” H.
Xu et al. examined research on the polarization
of microglia and their roles in the inflammation
response and secondary brain injury after TBI. It is
hoped that decreasing M1 phenotype and increasing
M2 phenotype may shed light on the pharmacotherapy
of TBI.

(iv) Studies to locate the clinical predictors of recovery
from prolonged disorders of consciousness (PDC)
can be arduous. In the original research presented
by H. Abe et al., 14 TBI patients were investigated
using diffusion tensor imaging (DTI) for longterm
follow-ups of 1-2 years. The results disclosed
correlation between initial severity of PDC and
difference in axial diffusivity (AD) and the degree
of recovery from PDC (RPDC). Microstructural
white matter changes in this study implicate their
possible relationship with the degree of RPDC.

(v) Efforts to correct behavioral, cognitive, mood, and
executive impairment of TBI patients are costly.
The article “Rehabilitation Treatment and Progress
of Traumatic Brain Injury Dysfunction” by B. Dang
et al. compiles the current rehabilitation treatment
plans and outcomes of TBI in adults.

(vi) Whether TBI induces substance-related disorder
(SRD) is currently debatable. C.-H. Wu et al. carried
out a cohort study of 19 thousand TBI adults
with no history of mental disorders prior to brain
injury in the original paper titled “Traumatic Brain
Injury and Substance Related Disorder: A 10-Year
Nationwide Cohort Study in Taiwan.” Results show
that the overall incidence of SRD was 3.62-fold
higher in the TBI group and 9.01-fold in the severe
TBI group. The severity of TBI seems to have
strong correlation in the subsequent risks of SRD.

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