Blueberries may improve attention in children following double-blind trial
October 13, 2017
Blueberries may improve attention in children following double-blind trial
Credit: University of Reading
Primary school children could show better attention by consuming flavonoid-rich blueberries, following a study conducted by the University of Reading.
In a paper published in Food & Function, a group of 7-10 year olds who consumed a drink containing wild blueberries or a matched placebo and were tested on their speed and accuracy in completing an executive task function on a computer.
The double blind trial found that the children who consumed the flavonoid-rich blueberry drink had 9% quicker reaction times on the test without any sacrifice of accuracy. In particular, the effect was more noticeable as the tests got harder.
Professor Claire Williams, a neuroscience professor at the University of Reading said:
“This is the first time that we have seen the positive impact that flavonoids can have on the executive function of children. We designed this double blind trial especially to test how flavonoids would impact on attention in young people as it’s an area of cognitive performance that hasn’t been measured before.
“We used wild blueberries as they are rich in flavonoids, which are compounds found naturally in foods such as fruits and their juices, vegetables and tea. They have been associated with a range of health benefits including antioxidant and anti-inflammatory effects, and our latest findings continue to show that there is a beneficial cognitive effect of consuming fruit and vegetables, tea, coffee and even dark chocolate which all contain flavonoids.”
The children were then asked to pay attention to an array of arrows shown on a PC screen and press a key corresponding to the direction that the central arrow was facing. The task was repeated over a number of trials, where cognitive demand was manipulated by varying how quickly the arrows appeared, whether there were additional arrows appearing either side of the central arrow, and whether the flanking arrows were pointing in the same/different direction as the central arrow.
Previous Reading research has shown that consuming wild blueberries can improve mood in children and young people, simple memory recall in primary school children, and that other flavonoid rich drinks such as orange juice can also improve memory and concentration.
The Wild Blueberry Association of North America provided a freeze-dried powder made from wild blueberries which was used in the study but did not provide any additional financial support and did not play a role in the design of the study.
Wild blueberries are grown and harvested in North America, and are smaller than regular blueberries, and are higher in flavonoids compared to regular varieties.
The double-blind trial used a flavonoid-rich wild blueberry drink, with a matched placebo contained 8.9g of fructose, 7.99g of glucose and 4 mg of vitamin C matching the levels of nutrients found in the blueberry drink.
The amount of fructose is akin to levels found in a standard pear.
This was an executive function task- requiring participants to pay attention to stimuli appearing on screen and responding correctly. The task was a simple one- responding to the direction of an arrow in the middle of a screen (by pressing left/right arrow key) but we then varied how quickly the stimuli appeared, whether there were additional arrows appearing either side of the stimuli and whether those flanking arrows were pointing in the same/different direction as the direction you had to respond.
There are 6 main classes of flavonoids:
Anthocyanins – found in berry fruits such as the blueberries used in this study and also in red wine.
Flavonols – found in onions, leeks, and broccoli
Flavones – found in parsley and celery,
Isoflavones – found in soy and soy products,
Flavanones – found in citrus fruit and tomatoes
Flavanols—found in green tea, red wine, and chocolate
Explore further: Wild blueberries could boost primary schoolchildren’s memory and concentration
More information: A. R. Whyte et al. The effect of cognitive demand on the performance of an executive function task following wild blueberry supplementation in 7 to 10 years old children, Food Funct. (2017). DOI: 10.1039/c7fo00832e
Peter Anderson. Assessment and Development of Executive Function (EF) During Childhood, Child Neuropsychology (2003). DOI: 10.1076/chin.188.8.131.5224
“Head-Eye Vestibular Motion Therapy Affects the Mental and Physical Health of Severe Chronic Postconcussion Patients”
CAPE CANAVERAL, Fla., Oct. 2, 2017 /PRNewswire/ — A recent peer-reviewed study published in Frontiers in Neurology: Neurotrauma Section (Impact Factor 3.552) showing “statistical and substantive significant decreases in Post Concussive Syndrome (PCS) symptom severity after treatment…” may suggest important improvements in treating sports-related head trauma.
Researchers from the Bedfordshire Centre for Mental Health Research in association with the University of Cambridge, University of Cincinnati, Carrick Institute, Plasticity Brain Centers and Harvard Macy– MGH Institutes studied whether head-eye vestibular motion (HEVM) therapy is associated with decreased symptoms and increased function in post concussive syndrome patients who have been severely impaired for greater than 6 months after a mild traumatic brain injury.
The investigators reviewed the medical records of 620 post-concussive patients exhibiting Post Concussive Syndrome. The inclusion criteria included only individuals who had sustained a sport-related concussion, had persistent and debilitating symptoms for greater than 6 months, and who had not responded to prior interventions. The selection of subjects based upon the defined criteria yielded a population sample of 70 patients.
As described in the text, each patient was assessed individually, utilizing instrumentation designed to measure and quantify over 40 variables such as symptoms, cognitive function, reaction time, vestibular-ocular function, gaze-holding, and eye-tracking.
The treatments that were administered consisted of the following five components, over a 5-day “intensive” period:
- Head-Eye Vestibular Movements (HEVM) performed 5 times per day.
- Head-Hand-Eye Coordination Movements performed 3 times per day.
- Vestibular-Only Therapies in a Multi-Axis Rotational Chair (MARC) were termed Head-Eye performed twice per day.
- Somatic-Sensory Limb Movements performed 3 times per day.
- Spinal Manipulation Therapy of the Cervical Spine performed when neck tightness prohibited proper head-eye tracking.
After a statistical analysis of these data, the researchers concluded that after 5 days of intensive treatment at their international brain rehabilitation center, there was a significant and substantial change in symptoms of individuals that had been diagnosed with refractory post-concussion syndrome related to a sports-injuries.
The authors also noted a few points of interest:
- The pre-treatment symptom scores did not predict how well someone would perform after treatment. This means that pre-existing symptoms did not correlate with post-treatment results. So patients with very severe symptoms did not have any worse results than those with mild symptoms.
- Irritability and sleep disturbances were the largest predictors of overall symptoms. It is uncertain whether this means that higher symptoms make people more irritable and less able to sleep soundly, or if people with irritability and difficulty sleeping have higher symptoms.
- There was a remarkable improvement in symptoms associated with mental health, such as irritability.
A 5-day intensive therapy scenario involving patient-specific vestibular, ocular, sensory, and physical therapies demonstrated to be an effective modality that might be considered in chronic treatment refractory PCS.
Widely accepted research suggests that Approximately 1.8–3.6 million annual traumatic brain injuries occur in the United States. Published research has demonstrated that the majority of symptoms that are associated with concussions resolve on their own within 14-30 days.
However, in about 10% of all cases the symptoms experienced after sustaining a head trauma enter a “chronic”phase, in which symptoms may persist for weeks, to months, or even permanently. Once symptoms are experienced for greater than three months, a patient may be diagnosed with post-concussion syndrome.
New Approach to Destroying Deadly Brain Tumors
Neuroscience NewsNEUROSCIENCE NEWSOCTOBER 10, 2017
BRAIN CANCERFEATUREDNEUROLOGY7 MIN READ
Summary: Researchers at UT Southwestern report medications used to treat arthritis and lung cancer may help in the battle against glioblastoma.
Source: UT Southwestern.
A new strategy for treating brain tumors may extend or save the lives of patients diagnosed with one of the deadliest forms of cancer, according to a study from UT Southwestern Medical Center.
The research demonstrates in mice that a combination of medications – traditionally used separately to treat lung cancer and arthritis – can destroy glioblastoma, a difficult-to-treat brain tumor that is lethal to most patients in little more than a year.
The combination of these medications disables two proteins responsible for helping the cancer cells survive, providing a therapy that UT Southwestern is working to fast-track for clinical use.
“This could be a groundbreaking treatment. If it works in patients, then it will be an important advance,” said Dr. Amyn Habib, a member of UT Southwestern’s Peter O’Donnell Jr. Brain Institute and the Harold C. Simmons Comprehensive Cancer Center.
The research published in Nature Neuroscience answers a decades-old question of why a treatment that disables a protein common in various cancers has been effective in some forms of lung and colon cancer but not in glioblastoma.
The protein, known as epidermal growth factor receptor (EGFR), resides in the tumor cell’s membrane and has been a traditional target for fighting malignant tumors. Dr. Habib’s team found that when doctors use a medication to disable the receptor, a second protein is produced in the brain that takes over the receptor’s function to keep the cancer cell alive.
The study shows that blocking both the receptor and the tumor necrosis factor (TNF) destroys the glioma tumors.
The medications used to disable these proteins are already approved by the U.S. Food and Drug Administration, including TNF inhibitors used to treat arthritis and other rheumatologic conditions. Dr. Habib said this could speed the effort at UT Southwestern to organize a clinical trial to test the treatment on lung cancer and glioblastoma patients.
“This is a terrific example of research that can be relatively quickly carried into the clinic,” said Dr. Habib, Associate Professor of Neurology & Neurotherapeutics.
Glioblastoma is the most lethal and common type of brain cancer, accounting for 17 percent of malignant brain tumors. The disease aggressively spreads through the brain and can prove fatal within months, though surgery, chemotherapy, and radiation treatments can often help patients survive more than a year.
UT Southwestern is testing an array of other approaches to improve the prognosis for patients, from protein-inhibiting medications to immunotherapy that uses the body’s immune system to fight cancer.
Dennis Kothmann, a retired math teacher with glioblastoma, hopes one of these approaches will work for him. While Dr. Habib’s treatment strategy is still being prepared for clinical use, Mr. Kothmann is participating in an immunotherapy clinical trial at UT Southwestern.
“Chemo hasn’t worked very well for other people with this disease,” he explained as a nurse prepared to deliver his latest infusion through his arm. “Why not try something different, give yourself a chance?”
The 71-year-old Fort Worth native was diagnosed with glioblastoma in November after seeking medical treatment for his headaches and vision problems. Mr. Kothmann tells his story with an inspiring air of positivity, his jovial smile belying the grim prospects for beating such a disease.
“There’s no sense in getting down,” Mr. Kothmann said, his wife Candace nodding in agreement next to him. “That’s not going to make me better.”
Imaging shows how a new treatment strategy gradually eliminated malignant brain tumors in mice. The images were taken every 10 days, with the tumor no longer visible after 20 days. UT Southwestern is working to fast-track the treatment for clinical use. NeuroscienceNews.com image is credited to UT Southwestern.
Dr. Habib is encouraged by the initial success of his protein-disabling strategy. But he acknowledges a cure may not be imminent because cancers tend to adapt to treatments and find other pathways to thrive if one is blocked.
For example, disabling the EGFR protein initially showed success in lung cancer patients, but over time the cells develop resistance to the medication.
“But if we can provide a remission or slowing of the disease and extend survival, that’s a big advance in fighting this devastating disease,” said Dr. Habib, also a staff physician at the North Texas VA Medical Center.
ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE
The study was supported by the National Institutes of Health, the Office of Medical Research, and Department of Veterans Affairs. Other collaborators at UT Southwestern include Dr. Gao Guo, a postdoctoral researcher in Dr. Habib’s laboratory, and Dr. Edward Pan, Associate Professor of Neurology & Neurotherapeutics, Neurological Surgery, Dr. Sandeep Burma, Associate Professor of Radiation Oncology, Dr. Kimmo Hatanpaa, Associate Professor of Pathology, Dr. Bruce Mickey, Vice Chairman and Professor of Neurosurgery, and Dr. David Wang, Associate Professor of Internal Medicine.
The Harold C. Simmons Comprehensive Cancer Center is the only NCI-designated Comprehensive Cancer Center in North Texas and one of just 47 NCI-designated Comprehensive Cancer Centers in the nation. Simmons Cancer Center includes 13 major cancer care programs. In addition, the Center’s education and training programs support and develop the next generation of cancer researchers and clinicians. Simmons Cancer Center is among only 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site.
Source: James Beltran – UT Southwestern
Image Source: NeuroscienceNews.com image is credited to UT Southwestern.
Original Research: Abstract for “A TNF–JNK–Axl–ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma” by Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao & Amyn A Habib in Nature Neuroscience. Published online June 12, 2017 doi:10.1038/nn.4584
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UT Southwestern “New Approach to Destroying Deadly Brain Tumors.” NeuroscienceNews. NeuroscienceNews, 10 October 2017.
A TNF–JNK–Axl–ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma
Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild-type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in turn of c-Jun N-terminal kinase (JNK), the Axl receptor tyrosine kinase and extracellular signal-regulated kinases (ERK). Inhibition of this adaptive axis at multiple nodes rendered glioma cells with primary resistance sensitive to EGFR inhibition. Our findings provide a possible explanation for the failures of anti-EGFR therapy in GBM and suggest a new approach to the treatment of EGFR-expressing GBM using a combination of EGFR and TNF inhibition.
“A TNF–JNK–Axl–ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma” by Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao & Amyn A Habib in Nature Neuroscience. Published online June 12, 2017 doi:10.1038/nn.4584
Two brain regions—the medial frontal and lateral prefrontal cortices—control most executive function. Robert Reinhart used high-definition transcranial alternating current stimulation (HD-tACS) to synchronize oscillations between them, improving brain processing. De-synchronizing did the opposite.
Robert Reinhart calls the medial frontal cortex the “alarm bell of the brain.”
“If you make an error, this brain area fires,” says Reinhart, an assistant professor of psychological and brain sciences at Boston University. “If I tell you that you make an error, it also fires. If something surprises you, it fires.” Hit a sour note on the piano and the medial frontal cortex lights up, helping you correct your mistake as fast as possible. In healthy people, this region of the brain works hand in hand (or perhaps lobe in lobe) with a nearby region, the lateral prefrontal cortex, an area that stores rules and goals and also plays an important role in changing our decisions and actions.
“These are maybe the two most fundamental brain areas involved with executive function and self-control,” says Reinhart, who used a new technique called high-definition transcranial alternating current stimulation (HD-tACS) to stimulate these two regions with electrodes placed on a participant’s scalp. Using this new technology, he found that improving the synchronization of brain waves, or oscillations, between these two regions enhanced their communication with each other, allowing participants to perform better on laboratory tasks related to learning and self-control. Conversely, de-synchronizing or disrupting the timing of the brain waves in these regions impaired participants’ ability to learn and control their behavior, an effect that Reinhart could quickly fix by changing how he delivered the electrical stimulation. The work, published October 9, 2017, in the journalProceedings of the National Academy of Sciences (PNAS), suggests that electrical stimulation can quickly—and reversibly—increase or decrease executive function in healthy people and change their behavior. These findings may someday lead to tools that can enhance normal brain function, possibly helping treat disorders from anxiety to autism.
“We’re always looking for a link between brain activity and behavior—it’s not enough to have just one of those things. That’s part of what makes this finding so exciting,” says David Somers, a BU professor of psychological and brain sciences, who was not involved with the study. Somers likens the stimulation to a “turbo charge” for your brain. “It’s really easy to mess things up in the brain but much harder to actually improve function.”
Research has recently suggested that populations of millions of cells in the medial frontal cortex and the lateral prefrontal cortex may communicate with each other through the precise timing of their synchronized oscillations, and these brain rhythms appear to occur at a relatively low frequency (about four to eight cycles per second). While scientists have studied these waves before, Reinhart is the first to use HD-tACS to test how these populations of cells interact and whether their interactions are behaviorally useful for learning and decision-making. In his work, funded by the National Institutes of Health, Reinhart is able to use HD-tACS to isolate and alter these two specific brain regions, while also recording participants’ electrical brain activity via electroencephalogram (EEG).
“The science is much stronger, much more precise than what’s been done earlier,” says Somers.
In his first round of studies, Reinhart tested 30 healthy participants. Each subject wore a soft cap fitted with electrodes that stimulated brain activity, while additional electrodes monitored brain waves. (The procedure is safe, noninvasive, and doesn’t hurt, says Reinhart. “There’s a slight tingling for the first 30 seconds,” he says, “and then people habituate to it.”) Then, for 40 minutes, participants performed a time-estimation learning task, pressing a button when they thought 1.7 seconds had passed. Each time, the computer gave them feedback: too fast, too slow, or just right.
Reinhart tested each of the 30 participants three times, once up-regulating the oscillations, once disrupting them, and once doing nothing. In tests where Reinhart cranked up the synchrony between the two brain regions, people learned faster, made fewer errors, and—when they did make an error—adjusted their performance more accurately. And, when he instead disrupted the oscillations and decreased the synchrony—in a very rough sense, flicking the switch from “smart” to “dumb”—subjects made more errors and learned slower. The effects were so subtle that the people themselves did not notice any improvement or impairment in the task, but the results were statistically significant.
Reinhart then replicated the experiment in 30 new participants, adding another study parameter by looking at only one side of the brain at a time. In all cases, he found that the right hemisphere of the brain was more relevant to changing behavior.
Then came the most intriguing part of the study. Thirty more participants came in and tried the task. First, Reinhart temporarily disrupted each subject’s brain activity, watching as their brain waves de-synchronized and their performance on the task declined. But this time, in the middle of the task, Reinhart switched the timing of the stimulation—again, turning the knob from “dumb” to “smart.” Participants recovered their original levels of brain synchrony and learning behavior within minutes.
“We were shocked by the results and how quickly the effects of the stimulation could be reversed,” says Reinhart.
Though Reinhart cautions that these results are very preliminary, he notes that many psychiatric and neurological disorders—including anxiety, Parkinson’s, autism, schizophrenia, ADHD, and Alzheimer’s—demonstrate disrupted oscillations. Currently, most of these disorders are treated with drugs that act on receptors throughout the brain. “Drugs are really messy,” says Reinhart. “They often affect very large regions of brain.” He imagines, instead, a future with precisely targeted brain stimulation that acts only on one critical node of a brain network, “like a finer scalpel.” Reinhart’s next line of research will test the technology on people with anxiety disorders.
There is also, of course, the promise of what the technology might offer to healthy brains. Several companies already market brain stimulation devices that claim to both enhance learning and decrease anxiety. YouTube videos show how to make your own, with double-A batteries and off-the-shelf electronics, a practice Reinhart discourages. “You can hurt yourself,” he says. “You can get burned and have current ringing around your head for days.”
He does, however, see the appeal. “I had volunteers in previous research who came back and said, ‘Hey, where can I get one of these? I’d love to have it prior to an exam,'” he says. “That was after we debriefed them and they were reading the papers about it.”
Somers notes that there are still many questions to answer about the technology before it goes mainstream: How long can the effect last? How big can you make it? Can you generalize from a simple laboratory task too much more complicated endeavors? “But the biggest question,” says Somers, “is how far you can go with this technology.”
“Think about any given workday,” says Somers. “You need to be really ‘on’ for one meeting, so you set aside some time on your lunch break for some brain stimulation. I think a lot of people would be really into that—it would be like three cups of coffee without the jitters.”
Explore further: Electric ‘thinking cap’ controls learning speed
More information: Disruption and rescue of interareal theta phase coupling and adaptive behavior, PNAS(2017).