See inside the brain with CLARITY

Last year in 2012, Dr. Karl Desseiroth and colleagues from Stanford University published their technology, called CLARITY, in Nature, the most prestigious scientific journal in the world. CLARITY marks the start of a new chapter in brain imaging. Imagine being able to see through the brain in such a way that you can actually see neurons connect to each other. The YouTube video I have posted below describes their work which is truly exciting. Think about what this means for brain recovery and neuroplasticity research!!

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Real-world Challenges of Translating Research Evidence into Clinical Rehabilitation Practice (and vice versa!)

A wise person recently said to me “Sometimes I think the translational issue is one where therapists don’t want to listen, and researchers don’t want to communicate.”
I find myself in an interesting position as both ‘therapist’ and ‘researcher’ and even more convoluted; both ‘basic scientist in neuroscience’ and ‘clinical researcher’. I appreciate the challenges to knowledge translation that he mentions. Research and the application of research to the clinical situation is a complicated issue that sometimes depends on the ‘hat’ you are wearing. When I wear my ‘scientist hat’ I think that clinicians should really seek out evidence-based practice however when I wear my ‘clinician hat’ I understand that in my hectic day I don’t have time to read the hundreds of articles published in my field every 6 months or so.
Researchers don’t seem to want to spend time synthesizing this research for me. Furthermore, in many cases, the studies are performed on specific patients in an ‘ideal’ environment that may or may not be applicable to my patients. The classic example of that is constraint-induced therapy which has been mostly studied in patients with very good hand recovery and no cognitive or memory impairments at all and no other health problems. These patients represent the minority of people I see. The clinician will argue that health researchers should really reach out and study what is really important on the frontlines. So I try not to get offended when wearing my hats. It is true that clinicians, basic scientists, clinical researchers, policy makers are all operating in their own silos and it takes quite a bit of momentum to get cross-talk. I know that the Heart and Stroke Foundation Partnership for Stroke Recovery and other organizations are working on this. I believe lack of communication has got to do with the comfort level that you have when finding yourself in an unfamiliar silo; sometimes you just have to admit that you really don’t understand the methods and applicability of someone else’s area. You just have to be open to learning and collaboration.
In terms of evidence-based practice, only a small fraction of what I do as a clinician has been tested and found effective in people with stroke. It is not that there is evidence to say that my technique does not work; there is just no evidence yet. I must rely on my clinical judgement as well as the advice from experienced and trusted colleagues and the outcomes I see right in front of me among the patients I work with. Researchers tend to study a discrete intervention, like muscle stimulation or treadmill training. Because patients are so different (I have never met two people with stroke who have the exact same recovery profile) I often have to take an eclectic approach derived from research in coaching/training and exercise, research in other conditions and my own creativity and ability to problem solve.True progress will happen when scientists, clinicians and patients collaborate to undertake studies that are grounded in real-world practices and challenges. You don’t have to be an expert in someone else’s area, you just have to be open to communication and sharing.

Sleep your brain healthy; Just press ‘SAVE’

Sleep is like the ‘SAVE’ icon on your computer. When you sleep, memories become more solidly formed and stored inside your brain. Studies in both humans and animals show that when you lose sleep, even for just a few hours per night, you develop memory problems. (Imagine not pressing the ‘SAVE’ button and losing precious information). You can imagine then, how important sleep becomes for a brain trying to relearn and rewire after brain injury (Please see my post from Jan 2012 on ‘Sleep and Brain Recovery’ for more discussion).

So what aspects of sleep are most important; total hours of sleep, naps, how long it takes to go to sleep, waking up at night, or daytime sleepiness? A recent study published in Sleep Medicine (May 2012) followed 2012 people over the age of 65 for 10 years. The study, a partnership between researchers at University of Cambridge, UK and University of South Australia (Keage 2012), found that older people who take a nap during the day are two thirds less likely to develop cognitive impairment 10 years later. The authors describe napping as ‘protective’ against cognitive decline.

Furthermore, sleeping less than 6 hours each night doubled the risk of cognitive impairment over 10 years. People who reported daytime sleepiness had 2.5 times the risk of developing cognitive impairment 10 years later. The results of this study suggest that to preserve brain health over the long term you should sleep between 6 and 9 hours per night and have about a 60 minute daytime nap.

Why is sleep so important? Well, studies show that people who experience sleep deprivation for 24 hours have higher levels of stress hormones in the blood (See my post “Chronic stress and depression is bad for your brain” November 2012). They also make more errors on thinking tests (Joo and group, Journal Clinical Neurology 2012). People with chronic insomnia have significantly lower scores on tests of attention and concentration. They have impaired memory and thinking compared to people who sleep normally (Noh and group, Journal Clinical Neurology 2012) and what is most alarming is that people with insomnia have shrinkage of a very important cashew-sized section of the brain critical for forming memories called the hippocampus. During medical sleep studies, insomniacs who have experienced insomnia longer and who are more restless at night, have more brain shrinkage and more cognitive impairment. These are clearly NOT GOOD THINGS!! So pay attention to sleep. It is very likely that a good night’s sleep (or a daytime nap) can, not help maximize your recovery from a brain injury, but also promote a healthy brain in the long term.

There are plenty of resources on the internet but to sleep your brain healthy, the Canadian Sleep Society (www.canadiansleepsociety.ca) recommends some basic habits to improve your sleep. Try these simple solutions first.
1. Go to bed only when sleepy and use a relaxing bedtime routine (bath, reading etc)
2. Remove noise, light and other distractions
3. Avoid caffeine, nicotine, and other stimulants
4. Avoid strenuous exercise, large meals or long naps close to bedtime

Exercise counteracts the harmful effects of chronic stress and depression on the brain

The concept that exercise is an effective treatment for depression is not new. The Cochrane Collaboration, an enormous network of scientific experts around the world recently published (Rimer et al July 2012) a review of 28 articles studying the effects of exercise on depression symptoms with a total of 1101 participants. They showed that exercise significantly improved symptoms of depression, although modestly, but the benefits were long lasting.

http://summaries.cochrane.org/CD004366/exercise-for-depression

Since we know that depression is a ‘condition of the brain’, what may be more interesting is studying the effects of exercise on the depressed (or stressed) brain. How does exercise affect the depressed brain? Is there is a level of exercise that is optimal in treating the harmful effects of stress and depression. What type of exercise (running, walking, strength training etc) is best?

In my previous post ‘Chronic stress and depression is bad for your brain’, I talked about how chronic stress activates the body’s hypothalamic-pituitary-adrenal (HPA) axis. Stress disrupts the delicate balance of neurotransmitters and other molecules in the brain, signaling the hypothalamus to release hormones which in turn signal the pituitary to activate the adrenal glands in the abdomen, just above the kidneys, to produce cortisol. Cortisol is not the bad guy- but prolonged high levels of cortisol disrupt the body’s homeostasis, weaken the immune system and impair memory (http://en.wikipedia.org/wiki/Cortisol). However, it is important to appreciate that the relationship between chronic stress and depression, cortisol and the neuroimmune response has not been completely mapped out. I will try to explain now how exercise fits in.

The key battleground between chronic stress on one side and exercise on the other is the neuroimmune system.  The neuroimmune system acts as the gatekeeper between the nervous system and the immune system. The nervous system especially the brain and spinal cord have a very privileged position in that they are separated and protected from infection and inflammatory cells circulating in the body (within the blood vessels). In animal studies, chronic stress and depression disrupts this balance and increases inflammation and production of free radicals within the brain as well as blunts the production of beneficial neurotrophins. Exercise on the other hand seems to work in the opposite direction: reducing inflammation, increasing anti-oxidant activity and enhancing production of neurotrophins (Refer to my post “Neurotrophins are brain fertilizers’).

One of the first studies examining how exercise could protect the brain from the harmful effects of stress was published in Neuroscience in 2004 (Adlard & Cotman). Rats were randomized to 3 weeks of running wheel exercise or to regular housing and then underwent a stressful event (enclosed in a small tube for 2 hours). They found that exercise protected the brain against the stress-induced decrease in the neurotrophin, BDNF.

Nakajima et al (2010 Behav. Brain Res.) showed that in rats receiving chronic severe immobilization stress (12 hours/day, 6 days/week for 5 weeks), there was accumulation of brain cell damage (lipid peroxidation), loss of the natural neurogenesis (growth of new neurons in the brain) and impaired cognitive function. Exposure to exercise between the exposures to immobilization stress reduced the severity of the harmful effects of stress.

Most of the research in the field is consistent with the concept that exercise is a potential treatment to reverse or limit the neuroimmune mechanisms related to stress-associated depression. The jury is out regarding the intensity, duration and type of exercise required but the general trend is a moderate (fast walking), regular (almost every day) approach.

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Chronic stress and depression is bad for your brain

Chronic stress disrupts the body’s natural balance (homeostasis) and induces a cascade of nasty events within the body’s endocrine and immune systems. In a system with normal homeostasis, each cell acts like an efficient miniature machine in which the cell happily functions because it receives the nutrients it needs to power its engines (the mitochondria), is safely protected by the cell membrane and is able to rid itself of waste.

Chronic stress causes the release of glucocorticoids from the adrenal glands. These harmful hormones disrupt the functioning of the mitochondria which impairs the working of cells especially neurons. We know that glucocorticoids (or stress hormones) result in the neuron not being able to support synaptic plasticity and the hormones slow the release of beneficial brain-derived neurotrophic factor (read my posts ‘Neuroplasticity is all about chemicals and synapses’ and ‘Neurotrophins are brain fertilizers’ for some background). The effects are most prominent in an area of the brain called the hippocampus which is critical for learning and memory. Furthermore, in animals, chronic restraint stress causes blunting of neurogenesis; the birth of new neurons in the hippocampus that seems to be important for making new memories. You can begin to see that chronic stress is going to create barriers to plasticity and recovery after a brain injury.

So how is chronic stress and depression related? Chronic stress in rodents (restraining them in a tube) consistently leads to depression-like behavior in the animals (Adlard & Cotman 2004). These animals go on to have impaired learning and memory and recent research supports the notion that chronic stress and depression also cause an increase in inflammation within the cells of the brain (Eyre & Baune 2012 Brain Behavior and Immunity 2012; Nakajima Behavioral Brain Research 2010). Inflammation damages the cell membranes and causes an accumulation of free radicals (the cells’ waste products). This is particularly hazardous to the healing brain!!

It is important to recognize that the emotional and psychological symptoms experienced in chronic stress and depression are due to altered homeostasis. It is physiological. The person’s delicate cellular balance is disrupted. Restoring this balance is important for a healthy and healing brain.

Coming up:  exercise to treat depression.

Non-invasive Brain Stimulation: The Basics

Sky News Australia, on July 12, 2012, reported “Revolution for Parkinson’s Treatment”. The Israel Ministry of Health on July 24, 2012 approved a Brainsway trial for treatment of autism. Google News reported on July 12, 2012, a promising treatment for swallowing problems after stroke.

All these news items have one thing in common; they all report on the potential of noninvasive brain stimulation for treatment of neurological conditions.

Stimulation of the brain ‘from the outside in’ has been around for decades (think about electroconvulsive therapy (ECT) for severe depression). On review of the research on the subject, there is fairly strong evidence that use of the brain stimulation technique, transcranial magnetic stimulation (TMS), improves symptoms of severe depression for patients who do not respond to usual treatment by medication. In 2008, the FDA in the US approved TMS for this purpose. TMS is not approved for use as a therapy for other conditions and is only available as part of a clinical research trial.  There are literally hundreds of research trials published and ongoing around the world. A search of PubMed using ‘transcranial stimulation’ in the title or abstract shows 8704 articles; the earliest published in 1956 but most beginning around 1987.  In 1991 there were 104 articles published in the field; 314 in 2001 and 969 on 2011. This is clearly a growing area of interest.

By stimulating the neurons within the brain, the researcher can influence the ‘talk’ or connection between neurons and neighbouring neurons; neuronal networks. This activation can ‘turn on’ areas that are not working properly or are perhaps sluggish. The biggest risk of this type of treatment is that turning on groups of neurons could cause an area of overactivity and possibly seizure. There have been a few seizures documented in relation to brain stimulation but this seems to be rare. The other theory is that activation of neurons can help to release neurotrophins that are important for neuroplasticity. In a review by Rothwell in 2012 (Clinical EEG and Neuroscience), he discusses that noninvasive brain stimulation may not be as beneficial on its own but is really a way to ‘prime’ the brain for new learning. When you pair the stimulation with a learning task such as memory training or training of the paralysed hand, the brain stimulation may enhance relearning. That is where there is real potential for recovery. The stimulation is really the potter’s clay and the therapy makes the sculpture.

There are two types of noninvasive brain stimulation techniques in the research literature, transcranial magnetic stimulation and transcranial direct current stimulation. There are subcategories within these two types of stimulation. TMS can be delivered in a continuous wave of stimulation, pulsed (repetitive or rTMS), or in a burst (theta-burst TMS). The other method of stimulation uses electrical rather than magnetic stimulation and can be delivered through transcranial direct current (tDCS) or pulsed current (tPCS). Using direct or pulsed current stimulation, researchers can either activate or silence groups of neurons by choosing to use either the positive or negative electrode over the target area. In most studies, the researchers are only able to stimulate the surface of the brain to a depth of about 1.5cm however some argue that intermittent methods of stimulation may stimulate deeper brain regions.

Wikipedia does a good job of explaining TMS (http://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation#FDA_actions). More research findings to follow in future posts!

Whole Body Vibration; Hype or a Real Shake-up?

Some time ago I found, on the inside front cover of my favourite physiotherapy journal, the image of an elderly woman sitting, legs outstretched, with her calves resting on a device advertised to improve circulation using vibration. My first step was to ‘Google’ it.  It appeared from this simple search that WBV was the answer to all your health needs; improving circulation, strength, energy, coordination, flexibility, and agility. Www.wholebodyvibration.ca reported that WBV improved health and well being and reduced pain, stress, fatigue, stress hormones and even fat and cellulite. Wikipedia wrote that in the short term, WBV stimulated muscle fibre contraction at a faster than normal rate thereby increasing circulation and increasing force production. In the longer term, the online encyclopedia quoted research claiming WBV improves bone mineral density and optimizes strength training. This seemed too good to be true but the research references definitely warranted a visit to PubMed so I carefully searched for articles on the topic. Searching ‘whole body vibration’ limited to human clinical trials among people with neurological disorders completed in the last 5 years, I found 14 articles. This review is not intended to be a systematic or comprehensive review of WBV, but a discussion of current evidence examining the usefulness of WBV as a therapeutic intervention in neurological disorders.

Background: WBV and Athletic training          

WBV is often combined with other exercises such as 30 second hold while in squat or lunge position; usually 3 times per week for 4 to 8 weeks. The vibration frequency, pattern (vertical or reciprocal), and amplitude vary within limits set by the particular machine. Recent well-controlled studies examining holding squat exercises with and without WBV in young adults (Corme 2006, Kvorney 2006) and older volunteers (Rees 2008, Bograts 2007) demonstrate that WBV training has no additional benefit on power of major lower extremity muscle groups compared to training alone (same exercises but with vibration platform turned off). Furthermore, WBV does not change thigh muscle oxygenation (amount of oxygen carried by the blood cells in the arteries within the muscle Cardinale 2007) or alter serum levels of testosterone or the trophic factor IGF-I (Cardinale 2006); nor does WBV with exercise enhance oxygen uptake over exercise alone in older and younger community dwelling volunteers (Cochrane 2008). Although WBV combined with static exercise increases perceived exertion, heart rate is not different between WBV with exercise and exercise alone (Cardinale 2007). This suggests that even though subjects perceive they work harder with WBV, their body’s indicators don’t show that. Not all studies have negative results however. WBV is superior to traditional stretching techniques in improving hamstring flexibility (Van den Tillan 2006) and WBV enhances thigh muscle strength in very weak subjects (Savelberg 2007). Overall these studies suggest that although WBV appears to improve strength, the additional benefits over traditional strength training are modest.

WBV and Parkinson’s disease

Three studies have examined WBV to reduce tremor, stiffness and improve balance in people with Parkinson’s disease (PD). In a well-planned study of 68 people with PD following 5 episodes of 1 minute variable frequency vibration, Haas (Neurorehab 2006) reported a significant (5 point) reduction in symptom severity score following WBV compared to a no intervention control. Biggest improvements were in tremor and stiffness scores but also in speed of movement and walking and posture scores up to 3 hours afterwards. WBV does not appear to improve balance when compared to conventional balance training using a wobble board or uneven surface practice (Ebersbach 2008) or walking (Turbanski 2005) in people with PD. In another study of 52 people with PD, Turbanski (2005) and colleagues measured balance using a computerized balance platform after 15 minutes of WBV or 15 minutes of indoor walking. Both groups had improved performance in narrow standing with the WBV group having additional improvement in balance with even narrower stance.

These studies suggest that WBV has a beneficial effect, in at least the short term, on some symptoms of Parkinson ’s disease and it is just as good as usual balance training to improve balance. It is probably better than doing nothing at all.

WBV in stroke rehabilitation

In a small study of 18 people, 15 to 50 days post-stroke, Tihanyi (2007) reported that WBV (1 min followed by 1 min rest six times) enhanced thigh muscle strength compared to simply standing on the WBV (without vibration). The study did not evaluate subjects beyond the immediate post-treatment phase so duration of the effect is not known. A larger well-controlled trial of WBV among 53 people at least 6 weeks post-stroke (Van Nees & Latour 2006) studied WBV or music/exercise therapy added to regular inpatient rehabilitation. Subjects had 30 minutes of either WBV or music and exercise group therapy, 5 days per week for 6 weeks with equal amounts of therapist contact. Both groups had equal gains in balance and function which was maintained at 6 week follow-up. WBV was just as effective as music/exercise therapy in combination with inpatient rehabilitation. Furthermore, there were no accidents or more participant drop-outs in the WBV group suggesting it was probably safe.

 WBV to treat MS symptoms

In one small trial among 12 people with multiple sclerosis (MS) (Schunfield 2005), subjects received one treatment of WBV or a nerve stimulation treatment (one minute with one minute rest, 5 times) and were evaluated immediately and one week afterwards. Speed of getting up and walking 10 feet decreased by one second in the WBV group compared to the nerve stimulation group at the follow-up. Computerized balance testing examining sway and response to being put off balance showed no difference between the two interventions. At least in the articles searched in the past 5 years, there is no evidence yet to suggest that WBV in people with MS improves symptoms.

 Is WBV harmful?

My PubMed search led me to a number of articles discussing occupational heath and safety in jobs in which workers (e.g. truck drivers, factory workers) are exposed to vibration. Occupational vibration is proposed to accelerate spinal joint and disc deterioration, hearing loss, and balance impairment. Abercrombie (2007) reports that the estimated vibration dose value of 17 is considered the upper limit of safe exposure. These researchers measured head and spine vibration during typical WBV treatment and they concluded that the transmitted forces through the head and spine are lessened when the knees are kept bent, suggesting positioning in a deep squat is important. These researchers also report that the acceptable limits of vibration exposure are exceeded during both vertical and reciprocal vibration (although reciprocal was less) and they recommend reciprocal (they term rotational) vibration with the knees flexed for durations less than 10 minutes in short bursts. This study points out that WBV may not be safe for everyone and WBV could worsen some conditions such as joint pain.

 Conclusions

Evidence seems to be growing that WBV as a specific intervention can improve bone density, muscle mass and peripheral circulation (not described here). Intuitively, one can imagine the usefulness of such an intervention, however, the studies performed thus far were mainly in healthy individuals and there are few studies completed in people with health conditions. In people with Parkinson’s disease, WBV is as good as a traditional exercise program to improve balance and may be of additional benefit in the short term to reduce symptoms like tremor and slowness of movement. Overall, the findings to support WBV intervention as a method to increase strength and balance are not compelling when comparing to an equivalent intervention with matched therapist contact. However, WBV can be considered better than no treatment all. There has been very little research around safety of WBV and most intervention studies excluded individuals with bone, joint, metabolic, and vascular problems, so we really don’t know the effect of WBV on people with these conditions.

So is WBV hype or a real shake-up? For my population of patients (older people with neurological problems along with multiple other health problems), WBV is not an intervention I would choose based on the evidence thus far. An equivalent amount of therapist-guided conventional cardiovascular, strength, balance, and flexibility training probably has broader benefits. However, future work on the effect of vibration on bone density, peripheral circulation and spasticity will be intriguing.