Tuesday, 31 May 2016

Nurturing The Brain – Part 9, Blueberries

Astronauts on space missions can be exposed to radiation for long periods of time, which can pose significant dangers to their health. The fact that the administration of blueberry extract has been proposed as a preventive therapy to protect them from harmful radiation is a great indication of just how powerful these fruits might be.

The more blueberries are studied, the more evident it becomes that they are a superfood. Blueberries contain important biologically active compounds, such as polyphenols, phenolic acids, and vitamins, with countless beneficial effects. Within polyphenols, there are many different types of chemicals found in blueberries with great health benefits, such as flavonoids; these include anthocyanins, which are particularly interesting due to their potent antioxidant properties. Among fresh fruits and vegetables, blueberries are the ones that contain the highest concentration of anthocyanins.

Blueberries’ potent antioxidant effects are indeed their most outstanding property. This is important because oxidation in one of the main sources of cellular damage. A process known as oxidative stress can arise from an increase in oxidant factors known as reactive oxygen species. Although they are normal product of cellular metabolism, and quickly neutralized by antioxidant defenses in normal conditions, they may escape neutralization and give rise to oxidative stress. This can have serious consequences, leading to the development of several pathologies, particularly in aged subjects, who are more vulnerable to the effects of oxidative stress.

So, anything that provides an antioxidant effect can help counterbalance the detrimental effects of oxidative stress, as is the case with blueberries, which can be used to boost our endogenous antioxidant defense system. But blueberries’ benefits are not restricted to their antioxidant action; they also have anti-inflammatory, antimutagenic, antihypertensive and hypoglycemic effects, and are even inhibit different types of tumors.

Blueberries confer great cardiovascular protection. Their biologically active molecules can inhibit inflammatory responses in endothelial cells, the cells that form the lining of all blood vessels. This improves endothelial function and prevents the development of vascular diseases. Daily blueberry consumption can improve blood pressure, arterial stiffness, myocardial and coronary performance, and protect the heart against ischemia – the shortage of oxygen and glucose due to restricted blood supply.

The neuroprotective effects of blueberries

The increase in antioxidant defenses that blueberries can provide is relevant not only in vascular disorders, but also in neurodegenerative conditions. Oxidative stress is particularly harmful to the brain because of its higher oxygen demands compared with other tissues, and of the higher exposure to oxidative damage that it entails. In fact, oxidation is the main agent of many age-related and neurodegenerative diseases, giving rise to cognitive and motor impairments and to a decrease in the sensitivity to several neurotransmitters.

Various anthocyanins contained in blueberries are able to cross the blood brain barrier. Those have been detected in the brains of aged rats receiving a long-term blueberry-supplemented diet, specifically in brain regions which are important for learning and memory. Blueberries’ anthocyanins are effective in decreasing oxidative stress in neurons. By counterbalancing oxidative damage, the antioxidant action of blueberries may contribute to a delayed onset of aging signs or even reverse injuries that have already occurred.

An example of the latter is a study that showed that transgenic mice predisposed to the development of Alzheimer’s disease, whose diet was supplemented with blueberry extracts, demonstrated an improvement in neuronal signaling pathways with a neuroprotective effect. In this case, a genetic predisposition to cognitive deficits was counterbalanced through dietary changes, suggesting a direct effect of blueberries on genetic expression. This impressive ability has been further evidenced by studies showing a reduction of the expression of proinflammatory genes in advanced age rats to the levels of young animals, with a corresponding improvement in memory.

Blueberries can also induce an increase in neuronal plasticity and in the generation of new neurons in the hippocampus, having therefore valuable effect in memory and learning mechanisms. This has been verified by studies demonstrating that blueberry supplementation can induce improvements in spatial memory, long-term memory, and in the ability to learn new information in animal models of aging.

The vascular effects of blueberries can also manifest themselves in brain. It has been shown that blueberries are able to prevent cerebral damage induced by ischemia, reducing the neurological deficits and increasing neurogenesis in the affected areas.

Inflammation is another crucial driver of aging and neurodegeneration. Blueberry extracts also have potent anti-inflammatory effects, inducing a significant decrease in the production of proinflammatory molecules. These anti-inflammatory mechanisms can complement their antioxidant action, potentiating their overall neuroprotective effect, and having an anti-neurodegenerative action.

In models of neuronal inflammation, blueberry polyphenols were shown to attenuate learning impairment resulting from neurotoxicity, and to exert anti-inflammatory effects through changes in genetic expression associated with synaptic plasticity, leading to memory improvement and the improvement of cognitive performance in mice.

Most of this data comes from animal studies, but there is also evidence supporting these effects in humans – in a study where elderly subjects received blueberry juice supplementation for 12 weeks, it was shown that there was an improvement in memory tests and in mood. Also, a normalization of glycemic and insulin levels was detected, which can also contribute to a decrease in the levels of inflammatory mediators associated with neurodegenerative diseases.

So, although blueberries’ antioxidant power is their most recognized feature, they can actually be beneficial through many other mechanisms – they can regulate cellular balance by acting on gene expression, signaling pathways, and synaptic plasticity, for example. All these actions can give rise to anti-ageing, anti-inflammatory and antitoxic effects, leading to an improvement in motor and cognitive performance.

Given this broad range of beneficial actions, blueberry extracts promise a multitude of clinical applications, namely in the context of neurological disorders in which oxidative stress, inflammation, and neurodegeneration are associated – Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis… Just to name a few.


Chen, J., Zhao, Y., Tao, X., Zhang, M., & Sun, A. (2015). Protective effect of blueberry anthocyanins in a CCL4-induced liver cell model LWT – Food Science and Technology, 60 (2), 1105-1112 DOI: 10.1016/j.lwt.2014.10.010

Giacalone, M., Di Sacco, F., Traupe, I., Topini, R., Forfori, F., & Giunta, F. (2013). Antioxidant and neuroprotective properties of blueberry polyphenols: a critical review Nutritional Neuroscience, 14 (3), 119-125 DOI: 10.1179/1476830511Y.0000000007

Huang, W., Liu, Y., Wang, J., Wang, X., & Li, C. (2014). Anti-Inflammatory Effect of the Blueberry Anthocyanins Malvidin-3-Glucoside and Malvidin-3-Galactoside in Endothelial Cells Molecules, 19 (8), 12827-12841 DOI: 10.3390/molecules190812827

Huang, W., Zhu, Y., Li, C., Sui, Z., & Min, W. (2016). Effect of Blueberry Anthocyanins Malvidin and Glycosides on the Antioxidant Properties in Endothelial Cells Oxidative Medicine and Cellular Longevity, 2016, 1-10 DOI: 10.1155/2016/1591803

Johnson, S., Figueroa, A., Navaei, N., Wong, A., Kalfon, R., Ormsbee, L., Feresin, R., Elam, M., Hooshmand, S., Payton, M., & Arjmandi, B. (2015). Daily Blueberry Consumption Improves Blood Pressure and Arterial Stiffness in Postmenopausal Women with Pre- and Stage 1-Hypertension: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Journal of the Academy of Nutrition and Dietetics, 115 (3), 369-377 DOI: 10.1016/j.jand.2014.11.001

Krikorian, R., Shidler, M., Nash, T., Kalt, W., Vinqvist-Tymchuk, M., Shukitt-Hale, B., & Joseph, J. (2010). Blueberry Supplementation Improves Memory in Older Adults

Journal of Agricultural and Food Chemistry, 58 (7), 3996-4000 DOI: 10.1021/jf9029332

Pojer, E., Mattivi, F., Johnson, D., & Stockley, C. (2013). The Case for Anthocyanin Consumption to Promote Human Health: A Review Comprehensive Reviews in Food Science and Food Safety, 12 (5), 483-508 DOI: 10.1111/1541-4337.12024

Shukitt-Hale, B., Carey, A., Jenkins, D., Rabin, B., & Joseph, J. (2007). Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging Neurobiology of Aging, 28 (8), 1187-1194 DOI: 10.1016/j.neurobiolaging.2006.05.031

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World No Tobacco Day, 31 May 2016: Get ready for plain packaging

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Monday, 30 May 2016

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Sunday, 29 May 2016

How mental health needs sleep – and vice versa

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A Resident’s Reflections from within the American Board of Psychiatry & Neurology (ABPN)

Most residents have a very limited understanding of the American Board of Psychiatry and Neurology (ABPN), and understandably so.

I myself thought of the ABPN as a large, bureaucratic, governmental organization that spent most of its time siphoning money from hapless residents in order to administer board certification examinations. I was therefore surprised, and a bit skeptical, when my chairman asked me if I was interested in a three-month administrative fellowship at the ABPN during my final year of neurology residency. Although I had an interest in administration, I was hesitant because I was unfamiliar with the fellowship’s objectives, because it would be the first year it was offered.

Three weeks before my administrative fellowship was to begin, a thick binder arrived containing a detailed, day-by-day schedule and multiple articles including, 10 Most Common Mistakes Made by Administrators and Understanding Financial Statements of Not-for Profits. I also received three books on self-improvement: Drive, Talent is Overrated, and, ironically, Being Wrong. Reviewing the schedule, I was surprised to see that I would be spending, collectively, almost four weeks traveling (including internationally).

The binder clearly spelled out the objectives of the fellowship. I was expected to learn about the mission and structure of the ABPN as a whole, and in particular the fiduciary responsibilities of the board of directors. I was to have scheduled meetings with the senior staff to appreciate their role in the day-to-day workings of the ABPN. In addition, I was expected to complete a research project, suitable for submission for presentation and publication. Finally, I was to have weekly meetings with Dr. Larry Faulkner, the President and CEO of the ABPN. It would be these weekly meetings that I would find most useful, as they provided perhaps the greatest educational value of the entire fellowship.

About the ABPN

Prior to my arrival at the ABPN, I learned that it had been formed by psychiatrists and neurologists in 1934 in order to distinguish qualified specialists from those offering neurological or psychiatric care without adequate experience or training.

Rather than a large, bureaucratic organization, the ABPN is relatively small. It consists of less than 40 staff, of which only one is a salaried physician (Dr. Faulkner). The ABPN sitting directors essentially volunteer their time. I quickly learned that the ABPN does not have members (unlike the American Academy of Neurology (AAN) or the American Psychiatric Association) and is an organization that is primarily responsible to the American public. Its main mission is to ensure the public that ABPN diplomates are competent to practice neurology and psychiatry. It does this by first certifying candidates who have graduated from accredited residency programs and by developing methods to assess that practicing physicians continuously keep up with the rapid pace of medical advancement. Initial certification for neurologists and psychiatrists now consists of a computer based examination.

Interestingly, the ABPN is also a driving force behind residency education. Recently, the Accreditation Council of Graduate Medical Education (ACGME) decided that it would not accredit additional combined training programs. Instead of dissolving these programs (in which almost 200 residents are currently enrolled), the ABPN decided to review and approve these combined training programs which include neurology-internal medicine and neurology-psychiatry. While the ACGME establishes minimal requirements for neurology and psychiatry residency programs, the ABPN establishes the necessary pre-requisites a resident must have in order to be eligible to become board certified. Often the ACGME follows suit. For example, initially there was no ACGME requirement that a graduating neurology resident see a single critical care patient. The ABPN determined that an intensive care unit (ICU) clinical skill examination (CSE) would be required in order to apply for an initial board certification exam. Shortly thereafter, the ACGME adopted the ICU CSE as a requirement for residency accreditation.

A recent focus of the ABPN is supporting education and research activities of academic faculty. Given the increasing clinical demands on faculty, I noted that the ABPN grants for innovative education projects placed particular emphasis on ensuring that faculty had protected time to complete those activities. The ABPN will shortly begin another grant program to support research on issues relevant to its mission. In both of the ABPN grant programs, awardees are selected by panels of neurologists and psychiatrists that includes members from within the academic community with established expertise in education or research.

Crucial Issue Forums

The ABPN has also begun to host a yearly “Crucial Issue Forum”. These Forums focus on pressing issues central to the fields of neurology and psychiatry and are used to obtain feedback from professional organizations and others on those issues. Experts in the field, including program directors, department chairs, representatives of national professional organizations, residents, and fellows are invited.

The most recent Forum focused on residency education, and included a discussion about whether the process of the CSEs should be modified to produce a more meaningful educational experience. A growing body of literature has suggested that the CSEs are not as effective as they might be. These sentiments were echoed by several residents, including myself. After attending this Forum, it became clear to me how seriously the ABPN took this Forum. Had the attendees of the Forum voted for the ABPN to conduct site visits to monitor the CSEs at every institution, it is likely that we would have site visits. Conversely, if a clear consensus had been to abolish the CSEs, it is likely that they would no longer exist.

My fellowship

A requirement of the fellowship is a research project with the expectation of publication. Several opportunities exist towards this end, including use of the ABPN’s wealth of data on their initial certification examinations, maintenance of certification exam and CSEs. Given my preexisting interest in both headache and education I surveyed adult neurology residency program directors and chief residents to determine their views on the appropriate amount of headache education in neurology residency. The goal of this project was to determine if headache education had significantly increased from a decade ago when a similar survey had been done. I had the opportunity to present the results to the senior staff of the ABPN as well as at the American Headache Society Annual Scientific Meeting in June 2015. The manuscript was accepted for publication in Headache, The Journal of Head and Face Pain.

The most memorable moments of my fellowship were spent in Dr. Faulkner’s office for our weekly 10 o’clock meetings. These ‘one on one’ meetings typically lasted between 1-2 hours. Rarely was there a set agenda. We discussed everything from Dr. Faulkner’s top ten rules for financial investment, to the inexact science of hiring employees. We talked about the slim evidence base behind maintenance of certification (MOC) and the impetus to have an MOC program despite the lack of strong evidence. We explored why continuing medical education (CME) has not met the same opposition as MOC Part IV, despite the fact that CME is the most time intensive component of MOC.

Behind the backdrop of the formal curriculum, readings, and scheduled meetings, a large part of the fellowship consisted of informal education. Every moment of downtime with Dr. Faulkner was an opportunity for me to learn about the process of becoming a successful administrator. While we waited for our flights we would often talk about everything from family to how important it is to take care of oneself physically and mentally. As Dr. Faulkner put it, “If you fall apart, everything falls apart. If you’re not healthy, you won’t be able to fulfill your family, social, or work responsibilities.” He impressed upon me the importance of being on the same page as one’s spouse and family. We discussed the value of doing a few tasks, but doing them well. I understand now that the real value of this unique experience truly lay in the in-depth immersion that I had into all things administrative, from the ABPN, to academic departments, to professional organizations, and even to my family.

Finally, the fellowship gave me the opportunity to meet with some of the most influential leaders in neurology and psychiatry. It was eye-opening to see the work that goes on behind the scenes at organizations like the AAN, APA, and ACGME. Despite their different responsibilities, each of these national organizations and their respective leaders had the singular goal of furthering the fields of neurology and psychiatry through focused initiatives. I began to appreciate the extraordinary effort that went into the large annual professional meetings. I spent a day at the AAN in Minneapolis learning about their different sections and the spectrum of resources they provide for their members. It was humbling to realize that I could probably spend my whole life on the AAN website and still not be able to take advantage of all the resources they have to offer.

In the ABPN I found an organization that not only tried to uphold the standards that make our profession credible, but also an organization that was dedicated towards the advancement of neurology and psychiatry education. In Dr. Faulkner I found a leader who tried to be fair. He cultivated the potential of those around him into a kinetic energy that translated into a collective success. Much of his time was spent advocating for the best interests of neurologists and psychiatrists against those who would like to propose greater physician scrutiny and regulation.

The mounting pressures of lower reimbursement in the setting of higher patient volumes, the oft-repeated mantra of ‘Do more with less’, and the overwhelming paperwork often overshadow our initial motivation to become physicians. More than anything else, my time at the ABPN and my interaction with the leaders in neurology and psychiatry have given me hope and optimism that we can find our way through the pressured maze of bureaucracy and increasing scrutiny to an era where we will be able to provide the best care for our patients while seamlessly documenting the quality of our work. There are multiple initiatives towards this end, not the least of which is the commitment and support of leaders in neurology to the AAN Axon Registry. In summary, my experience at the ABPN taught me that our future is in our hands and that our collective involvement and effort will be crucial to effectuate the outcomes we desire.


ABPN Awards Program. Faculty innovation in education award. American Board of Psychiatry and Neurology website. Accessed December 21, 2015.

Aminoff, MJ. Faulkner RF. (2012). The American Board of Psychiatry and Neurology, Looking Back and Moving Ahead. Arlington, VA: American Psychiatric Publishing.

Kay, Jerald. (1999(. Administrative Mistakes Handbook of Psychiatric Education and Faculty Development. Washington D.C., American Psychiatric Press.

Schuh, L., London, Z., Neel, R., Brock, C., Kissela, B., Schultz, L., & Gelb, D. (2009). Education Research: Bias and poor interrater reliability in evaluating the neurology clinical skills examination Neurology, 73 (11), 904-908 DOI: 10.1212/WNL.0b013e3181b35212

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What does ‘natural’ mean? Time to ditch a dangerous concept

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Saturday, 28 May 2016

Sixty-ninth World Health Assembly closes

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WHO seeks to allay Zika Olympics fears

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WHO public health advice regarding the Olympics and Zika virus

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VIDEO: Call for Olympic Games move over Zika

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Friday, 27 May 2016

Alzheimer’s may be caused by brain’s sticky defence against bugs

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Sixty-ninth World Health Assembly update

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UK to trial HPV vaccine in gay men but no plans yet for all boys

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Neurofeedback Therapy for The Management of Pain

Pain is a subjective feeling that can be influenced by sensory, affective, and cognitive factors. Chronic pain can have a widespread impact on overall brain function, and both cognitive and psychological factors play key roles in the development and management of pain.

Patients with long-term pain often present structural and emotional impairments associated with cortical regions of the brain that are linked not only to pain itself, but also to the many co-morbidities that often develop in association with chronic pain: depression, anxiety and sleep disturbances, for example.

Patients with chronic pain may require long-term pharmacological treatment; this entails a number of drawbacks mainly due to the undesirable side-effects that often arise with a continued use of analgesic drugs. There is a constant search for better pain management options, including non-pharmacological approaches. In the last decades, neurofeedback has been gaining ground as a potentially successful option.

What is neurofeedback?

Neurofeedback is a form of biofeedback. Biofeedback was born from the observation that one can control and manipulate certain bodily functions by being aware of them. By using instruments that measure physiological activity such as heartbeat, breathing, muscle activity, or skin temperature, a subject can receive fast and accurate information regarding those functions. The use of these monitoring systems allows the perception of the physiological functions, and in turn, and along with changes in thinking, emotions, and behavior (and adequate training), this allows the manipulation of those functions.

Biofeedback is widely applied to processes associated with the autonomic nervous system, such as heart rate, breathing rate or muscle tone. Biofeedback may be used to control those processes, and to improve health and physical performance. Over time, these changes can become long-lasting, enduring even without the continued use of monitorization instruments.

In the case of neurofeedback, these biofeedback techniques are applied to the brain. Neurofeedback, also known as EEG-biofeedback, uses electroencephalograms (EEG) to monitor brain waves, producing a signal that can be used as feedback to learn how to self-regulate brain functions. Lately, other monitorization techniques have begun to be applied, namely functional magnetic resonance imaging (fMRI) biofeedback.

It has actually been known for decades that, with adequate training, brain waves can be controlled. Intellectual activity induces fluctuations in cerebral bioelectric activity that can translate into neurophysiological changes. By understanding the association between the bioelectric activity of different brain areas and the associated cognitive, emotional, behavioral, or even pathological processes, neurofeedback can allow the modification of those specific processes.

Neurofeedback has proven useful in inducing relaxation and attention, in enhancing creativity, and as a therapy for a number of contexts – sleep disorders, epilepsy, depression, anxiety, language processing, neurorehabilitation in stroke, or enhancement of perception and learning. Another context in which neurofeedback has shown interesting effects is chronic pain.

Neurofeedback and pain management

Neurofeedback can have a direct influence on the processing of pain. By learning self-regulation of brain functions, a patient can modify the electrical activity of areas of the brain involved in pain processing, pain perception, or pain memory. This allows the reduction or even elimination of pain, along with many of its co-morbidities, including depression or anxiety, for example.

The psychological factors that influence pain perception have the ability to modify our body’s biochemical processes. Thoughts can have a direct impact on these processes and potentially produce analgesia. In fact, there is evidence indicating that cognitive control of pain can have a direct effect on opiod activity, stimulating the production of endorphins.

Another mechanism through which neurofeedback can modulate pain is the regulation of the emotional component of pain. The frontal cortex is associated with the feeling of unpleasantness associated with pain, and neurofeedback training applied to this region of the brain has been found to be able to induce changes in pain affect in patients with acute and chronic pain syndromes, leading to an increased pain tolerance.

Chronic pain can also induce changes in the functional organization of the brain. Neurofeedback can allow the control of pain by altering the connectivity between brain regions, thereby inducing long-lasting changes in neuronal networks that can counterbalance the changes induced by chronic pain.

Indeed, clinical data has demonstrated the efficacy of neurofeedback therapy in a number of chronic pain conditions: it can decrease headache intensity, being particularly effective in children and adolescents, as well as migraine and pain associated with fibromyalgia. Neurofeedback can also be effective in post-operative pain and in cancer pain.

During the last decades, neurofeedback training approaches and protocols have been steadily improving, along with its efficacy. As new methods arise, it is likely that neurofeedback can gain awareness and importance as a non-pharmacological therapy for a multitude of disorders. fMRI imaging, for example, can be a great upgrade for this therapy by allowing the detection of brain areas affected by chronic pain, and consequently allowing a more targeted intervention.

If one can learn to directly control the activation of specific brain regions, one can potentially be able to control neurophysiological mechanisms that may help in the treatment of disease.


Bandura, A., O’Leary, A., Taylor, C., Gauthier, J., & et al, . (1987). Perceived self-efficacy and pain control: Opioid and nonopioid mechanisms. Journal of Personality and Social Psychology, 53 (3), 563-571 DOI: 10.1037/0022-3514.53.3.563

deCharms, R., Maeda, F., Glover, G., Ludlow, D., Pauly, J., Soneji, D., Gabrieli, J., & Mackey, S. (2005). Control over brain activation and pain learned by using real-time functional MRI Proceedings of the National Academy of Sciences, 102 (51), 18626-18631 DOI: 10.1073/pnas.0505210102

Gorini, A., Marzorati, C., Casiraghi, M., Spaggiari, L., & Pravettoni, G. (2015). A Neurofeedback-Based Intervention to Reduce Post-Operative Pain in Lung Cancer Patients: Study Protocol for a Randomized Controlled Trial JMIR Research Protocols, 4 (2) DOI: 10.2196/resprot.4251

Ibric, V., Dragomirescu, L., & Hudspeth, W. (2009). Real-Time Changes in Connectivities During Neurofeedback Journal of Neurotherapy, 13 (3), 156-165 DOI: 10.1080/10874200903118378

Kumano, H., Horie, H., Kuboki, T., Suematsu, H., Sato, H., Yasushi, M., Kamei, T., & Masumura, S. (1997). EEG-driven photic stimulation effect on plasma cortisol and beta-endorphin. Applied Psychophysiology and Biofeedback, 22 (3), 193-208 DOI: 10.1023/A:1026215910176

Litt, M. (1988). Self-efficacy and perceived control: Cognitive mediators of pain tolerance. Journal of Personality and Social Psychology, 54 (1), 149-160 DOI: 10.1037/0022-3514.54.1.149

Megumi, F., Yamashita, A., Kawato, M., & Imamizu, H. (2015). Functional MRI neurofeedback training on connectivity between two regions induces long-lasting changes in intrinsic functional network Frontiers in Human Neuroscience, 9 DOI: 10.3389/fnhum.2015.00160

Nestoriuc, Y., Martin, A., Rief, W., & Andrasik, F. (2008). Biofeedback Treatment for Headache Disorders: A Comprehensive Efficacy Review Applied Psychophysiology and Biofeedback, 33 (3), 125-140 DOI: 10.1007/s10484-008-9060-3

Nestoriuc, Y., & Martin, A. (2007). Efficacy of biofeedback for migraine: A meta-analysis Pain, 128 (1), 111-127 DOI: 10.1016/j.pain.2006.09.007

Prinsloo, S., Gabel, S., Lyle, R., & Cohen, L. (2013). Neuromodulation of Cancer Pain Integrative Cancer Therapies, 13 (1), 30-37 DOI: 10.1177/1534735413477193

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