A ‘cure’ for binge drinking; food ‘networks’ and dementia; and easy, cheap blood test for Alzheimer’s
Lockdown measures across the world have brought many scientific investigations to a sudden halt. But, that hasn’t stopped neuroscientists from coming up with ingenious ways to collaborate and churn out breakthrough study after study in the age of social distancing. From new insights on how the foods we eat together can affect the brain to a new test that can detect Alzheimer disease in regular blood samples, stay in the know with this week’s NeuroBrief.
More than 100 years after his significant contributions to the field of neuroscience, Korbinian Brodmann is still best remembered for his classification of cortical areas based on histological characteristics (cell size, spacing or packing density, and lamination). In 1909, the German neurologist published his original research on cortical cytoarchitectonics, in which he mapped the human brain into 47 different areas—now known as Brodmann areas—by individually identifying sections with a then-novel technique called Nissl staining. The technique shows the location of the cell body of a neuron. Several Brodmann areas have been linked to various nervous functions like hearing (areas 41 and 42) and vision (areas 17 and 18). Many neuroscientists have since built on Dr. Brodmann’s ideas, and his research has become a core aspect of today’s medical education, with few neurology textbooks failing to mention his maps that are still used today.
In the News
Food pairs and dementia. You are what you eat, as the old saying goes. And nothing could be truer when it comes to the brain: healthier diet = healthier mind. But, what if it’s not just what you eat? Apparently, the key to a healthy mind may lie not only in the foods you eat—but the foods you choose to eat together (and how often), according to new research.
Researchers in France performed a nested case-control study to find out whether dietary patterns affect dementia risk. They looked at data collected from 209 people with dementia and 418 matched, dementia-free controls, comparing foods eaten by the two groups. Each participant had filled out a single questionnaire 5 years before the study, detailing which foods they ate and how often. The researchers found no big differences in individual food choices and average food intakes between the two groups—but there was a huge difference in the overall food groupings or “food networks” most often consumed.
What’s a food network (besides a cable channel)? Glad you asked. Meat and potatoes can make up one, as a simplistic example. In this study, people with dementia were more likely to frequently eat and pair highly processed meats with starches like potatoes and alcohol. (Might be time to lay off the Big Mac and fries.) Not surprisingly, people without cognitive decline more often ate meals consisting of smaller, more diverse, healthier food networks that included seafood, fruit, and greens. Another testament to the power of the Mediterranean diet, it seems.
A possible ‘cure’ for binge drinking? We’ve all likely been in situations where we knocked back a few too many, maybe at a backyard barbecue or a family reunion. (Though, perhaps not recently.) But, what exactly drives our need for one more pint? While no one knows for sure, researchers have gotten one step closer to untangling the mystery. A team of NIH-funded researchers have found that turning off a stress-signaling system in a brain region known for motivation and emotion-related behaviors can reduce binge drinking. (Binge drinking here refers to 4 or more standard drinks for a woman or 5 or more standard drinks for a man, imbibed over 2 hours.)
The researchers took a closer look at the opioid-receptor system—a well-known culprit behind many addictions like narcotics—as a potential means for curbing binge drinking. The interesting part? They chose to home in on a non-pleasure–inducing type of opioid receptor: the kappa opioid receptor. So, instead of making you feel all warm and fuzzy, these receptors produce feelings of stress and discontent. When people finish drinking and start to feel symptoms of withdrawal (like nausea and headache), that’s the kappa opioid-receptor system kicking in.
Using a binge-drinking mouse model, in which mice drank freely for 4 hours every night—enough time for them to achieve binge-worthy blood alcohol levels—the researchers found that deactivating the kappa opioid receptors in the brains of mice decreased binge-like drinking. Instead of downing a whole six-pack, these mice stopped at just one. Smart choice if you ask us.
But, why would turning off these negative receptors reduce binge drinking? Seems counterintuitive, right? Although it’s not entirely clear why blocking these receptors works, it is clear that the kappa opioid-receptor system is an important player when it comes to withdrawal and binge drinking itself. Sounds good enough for now.
Sugar cravings: It’s not just your taste buds. Many of us have tried artificially sweetened “diet” food products—like soda or cookies—that leave us jonesing for the real thing. Why is it that we’re left so unsatisfied after we’ve had them? It seems that a specialized, backchannel neural circuit may be to blame. For the first time, researchers have found that in addition to the taste receptors that signal the brain when sugar hits the tongue, there are unique sensor molecules in the gut that respond specifically to sugar but not artificial sweeteners. When these sensor molecules are tripped, the brain receives specific sugar-related information directly from the gut. The gut-to-brain circuit’s response may explain why artificial sweeteners often don’t satisfy sugar cravings. Although it could just be that artificially sweetened brownies taste more like a punishment than a dessert.
But, back to the science: To reach this conclusion, neuroscientists tested whether mice would prefer sugar over the artificial sweetener acesulfame K. Mice were offered water with either artificial sweetener or sugar. Initially, they drank both. But within 2 days, the mice switched almost exclusively to sugar water. (Even mice with genetically deleted sweet receptors preferred sugar—a finding supported in other studies.) By visualizing brain activity when the mice drank sugar vs artificial sweetener, the researchers discovered the brain region that responds exclusively to sugar: the caudal nucleus of the solitary tract (cNST), located in the brain stem—and separate from where mice process taste. The path to the cNST starts in the lining of the intestine, where sensor molecules trigger a signal that travels to the brain, mediated by the vagus nerve. In short, our gut craves sugar independently from our taste buds.
Although this study was done in mice, the same sugar-sensing neural circuit likely exists in humans. These findings help explain how our brains drive sugar cravings. The neuroscientists hope that their research will shed light on new targets to help curb our need for sweet treats.
What’s the scientific term for the electric charge that propagates down the axon of a neuron onto other neurons when the cell depolarizes enough to reach its threshold?
If you guessed “action potential,” you’re right! (And if you guessed “spike” or “impulse,” you were on the right track; both terms are neuro lingo for action potential.) Basically, action potential is an explosion of electrical activity that occurs because of a depolarizing current. Action potentials occur at the axon hillock—the part of the neuron that connects the cell body to the axon. They propagate down the axon without losing strength through saltatory conduction, which is essentially the action potential jumping from one node of ranvier (a gap in the myelin sheath in the axon) to the next.
Ordinary blood test for Alzheimer disease. Ever wish there was an easy way to screen for Alzheimer disease (AD)? Well, consider your wish granted. Researchers have made a simple, cheap blood test for easier detection of the neuro disease. AD is currently diagnosed using a series of physical, memory, and imaging tests. But, this new blood measures P-tau181—a tau protein variant—in regular blood samples.
P-tau181 is usually measured through cerebrospinal fluid (CSF) since it’s found in much higher levels there than in blood samples. But, CSF tests are expensive and difficult to perform. This led researchers to establish tau pathology through ordinary blood tests. They were able to do so using Single Molecule Array (Simoa), an ultrasensitive method that can measure much lower levels of protein biomarkers than other analytical methods. Using Simoa, the researchers compared p-tau181 levels in blood samples against established CSF and PET biomarkers from 1,131 individuals with cognitive decline—including AD, mild cognitive impairment, frontotemporal dementia, and other neurodegenerative disorders—and age-matched controls.
Results revealed very high P-tau181 levels in AD, even in early stages, but these raised levels were only found in patients who also had amyloid plaques. P-tau181 levels in the blood were also comparable with amyloid plaques detected using PET, and the new blood test was able to flag people with signs of early AD—something PET couldn’t do. Best of all? The test could distinguish AD from other similar brain diseases like frontotemporal dementia and Parkinson disease. The researchers are hopeful that their test will be a useful screening diagnostic in primary care.
MRI could prevent brain surgery. In the future, patients with brain cancer may not need to get biopsies for treatment planning, all thanks to AI (luckily, not the Terminator variety). New tech created by researchers at UT Southwestern can spot a specific mutation in a glioma tumor by analyzing 3D brain images. Unlike other methods that need to establish tumor boundaries before being able to pick up on mutations, the new diagnostic is an all-in-one, running on a single algorithm. Plus, it’s 97% accurate—surpassing other leading techniques (less than 90%). Sounds a little too good to be true…
So, how’d they do it? The researchers used an MRI-based deep-learning network to detect isocitrate dehydrogenase (IDH) gene mutations, which trigger brain tumor growth. (IDH mutation status can help guide clinicians on prognosis and treatment strategies.) They created two deep-learning networks that looked at brain MRI data from a publicly available databases of > 200 patients with brain cancer. One network used only T2-weighted images; the other used several MR imaging types. Since both networks were comparable in accuracy, the researchers determined that identification of IDH-mutated glioma could be done using only the T2-weighted images. They will be testing their model on larger datasets before deciding whether to incorporate it into clinical care. Their hope is to use AI to detect IDH-mutated gliomas in patients, and then use IDH inhibitors to block or reverse tumor growth without using surgery.
Sniff test for brain trauma. Could your ability to smell save your life? Catch a whiff of this: A new study shows that an easy, cheap “sniff test” could help doctors predict recovery and survival in patients with severe brain trauma and limited consciousness. Doctors need to distinguish patients who are minimally conscious from those who are in a vegetative state. Because it’s hard for doctors to diagnose a patient’s state of consciousness after severe brain trauma, inaccurate diagnoses are made roughly 40% of the time. So, an accurate diagnosis is important for optimal treatment strategies such as pain management, and also because it can underlie end-of-life decisions.
Researchers repeatedly exposed 43 patients with severe brain trauma and limited consciousness to different scents, monitoring sniff response each time. Jars of scents included shampoo, rotten fish, and no smell at all. Patients were exposed to each jar 10 times, in random order, for 5 seconds each time. Generally, when people smell something unpleasant, they automatically take shorter, shallower breaths—whether they’re conscious or unconscious—so the researchers used this as a marker for sniff response. All patients who reacted to the sniff test eventually regained consciousness, and more than 91% of these patients were still alive 3.5 years post-injury. Among those who did not respond, 63% died over follow-up. The researchers encourage immediate use of this new, simple diagnostic tool to identify potential recovery in unconscious patients with brain injury.
Are antibodies the answer for OCD? Ever find yourself constantly rearranging the objects on your desk until they’re “just right”? You might have OCD. Or you might just be very neat. Thankfully, if you do have compulsive tendencies, there’s a new, potentially safer treatment in the works.
In a new study, scientists found that patients with OCD have high levels of what they call Immuno-moodulin, or Imood for short (and no, it’s not an Apple product), a protein found in lymphocytes. On analyzing immune cells from 23 patients with OCD and 20 healthy volunteers, they found that Imood levels were about 6 times higher in patients with OCD. Imood is thought to affect genes in brain cells linked to mental disorders like OCD. Much like with humans, mice with high Imood levels demonstrate anxious behaviors, like digging and over-grooming. When the researchers treated anxious mice with an Imood-neutralizing antibody, the mice’s anxiety levels were reduced, and their behavior normalized in a matter of days. In light of their findings, the scientists have filed a patent application for the antibody and are working with a biopharma company to create a potential antibody treatment for human patients. If developed and approved, the use of antibodies for mental disorders like OCD could drastically reduce the number of side effects often seen with traditional chemical drugs.
Less invasive treatment for neuropsych disorders. When stress hormones are out-of-whack, mental health disorders like depression and PTSD can go from bad to worse. But how exactly do these hormones affect neuropsych disorders? It’s still unclear, but researchers have recently created a new way to remotely control the release of stress hormones from the adrenal gland—all by using magnetic nanoparticles. Their new method could help shed more light on the stress hormone-mental health link. It may also offer new ways to treat hormone-linked disorders and chronic pain. Still not impressed? Well, the study is gaining interest, given the potential to treat disorders with minimally invasive organ manipulation vs more risky approaches that can damage organ tissue like device implants.
To control stress hormone release, researchers created specialized magnetic nanoparticles that could be injected into the adrenal gland. The particles heat up when exposed to a weak magnetic field, which triggers heat-responsive channels to activate the hormone’s release. For hormone release stimulation, they targeted ion channels that control calcium flow into adrenal cells. When calcium passes through these open ion channels into adrenal cells, the cells begin releasing hormones. The heat-sensitive channel that they targeted, TRPV1, is found in many sensory neurons throughout the body.
The researchers injected these particles directly into the adrenal glands of rats. When the rats were exposed to a weak magnetic field (about 100 times weaker than those used for MRI), the particles heated up (by roughly 6 °C), which allowed the calcium ion channels to open without damaging any surrounding tissue. The stimulation doubled cortisol production and boosted noradrenaline by about 25%.
Along with treating stress disorders, the researchers speculate that their strategy could lead to treatment for pain, since TRPVI channels are often found in pain receptors. They also plan to see whether TRPVI exists in other peripheral organs like the pancreas, where remote hormone release could benefit a huge patient population.
New and improved schizophrenia drug. Schizophrenia treatment got you down? A new, experimental drug—dubbed SEP-363856—could provide symptom relief for people with schizophrenia but without the bothersome side effects of current drugs. The study results come as a breath of fresh air to the millions of people who rely on problematic, decades-old, one-size-fits-all schizophrenia drugs to manage their symptoms.
Existing first-generation medications can cause motor impairments like tremors and coordination problems, while second-generation drugs can cause weight gain and high blood sugar and cholesterol levels—making adherence difficult with either option. A big plus to SEP-363856 is that the drug appears to be effective without producing common, harsh side effects. And, here’s where it gets really good: unlike current antipsychotics on the market—which only tackle a single area of schizophrenic symptoms (hallucinations, delusions, confused thoughts, etc)—SEP-363856 addresses multiple symptom groups at once, including “negative” symptoms. (“Negative” refers to what’s lost in a patient, like symptoms of flattened emotions and social withdrawal.) Current standard schizophrenia meds don’t help ease “negative” symptoms. If that doesn’t scream “game changer,” we don’t know what would.
Researchers carried out a randomized trial that looked at the safety and efficacy of SEP-363856 in adults with acute exacerbation of schizophrenia. All were early on in disease course. Patients were randomized to receive either once-daily oral SEP-363856 (50 mg or 75 mg; n = 120) or placebo (n = 125) for 4 weeks. In just over a month, the drug helped manage several different schizophrenia symptoms, including delusions, hallucinations, flattened emotions, and social withdrawal. Among those who took the study drug, 65% responded by week four vs 44% who took placebo. And efficacy was maintained over a 6-month extension study. The researchers are hopeful that their findings will lead to a new, better treatment option for schizophrenia. They plan to undertake a larger trial of the drug for safety and efficacy as well as to see whether it can help people who’ve failed to respond to standard antipsychotics. We’ll be right here, cheering them on.
New in Patient Management
Spinal cord trauma and mental health disorders. When you’re sick, you’re often prescribed a large dose of…yup, bed rest. But, it turns out that bed rest can sometimes do more harm than good, especially when it comes to spinal cord injury (SCI). In fact, a new study shows that adults with SCI are at a higher risk of developing mental health disorders—like depression and anxiety—and secondary chronic diseases, compared with adults without the condition. The likely culprit? Bed rest.
Researchers looked at insurance claims data for a diagnosis of a mental health disorder in adults with and without traumatic SCI who were enrolled in a health insurance plan for ≥ 3 consecutive years. Overall, the incidences of anxiety disorders, depressive disorders, psychological multimorbidity, or having more than two mental health conditions were higher among those with SCI. Even after matching for demographics and chronic diseases, there was still much higher incidences of most psychological disorders and psychological multimorbidity among adults with SCIs. The researchers emphasized that doctors caring for adults with spinal cord injury need to be aware of the risk of mental health disorders in this population, especially in light of the social-distancing measures currently in place, as these patients are already socially isolated.
Adding insult to injury, people with SCI are often on bed rest for a long time, so they’re also at higher risk for chronic diseases like heart disease, diabetes, and liver disease, among others.
Alzheimer disease, drugs, and the gut. When it comes to your patients with Alzheimer disease (AD), do you ever prescribe drugs for other health conditions—like diabetes or high blood pressure—at the same dose as for patients without dementia? If so, you may need to make a few adjustments. A new study shows that AD could affect the way drugs are absorbed from the gut.
Where many scientists have focused on AD drug uptake across the blood-brain barrier, few have paid attention to other biological barriers like the intestine’s lining, which oral drugs need to pass through to get to the bloodstream. What little research there is indicates that AD could disrupt the absorption process. So, researchers investigated this disruption process with common AD drugs absorbed into the bloodstream through three different mechanisms. Using a mouse model of familial AD, the researchers measured plasma levels of caffeine and diazepam, digoxin, and valsartan. They found that blood plasma levels of diazepam were similar in mice with and without AD, but mice with AD had less valsartan and digoxin in their plasma than control mice.
Based on their previous investigations, the researchers suggested that transporters that help these drugs pass through intestinal cells may be disrupted by AD. These findings still need to be tested in humans, but if they’re true, then physicians will need to revisit their dosing regimens for certain drugs in this patient population.
Exercise’s effect on stroke damage. We all know that exercise can do a world of good for your health. But, when it comes to stroke survivors, you might want to be careful how much exercise—and at what intensity—you advise for recovery. Obviously, you aren’t going to recommend they shoot for Mr. Olympia, so what’s the right Rx? Apparently, the key to a speedy recovery is lots of light, daily physical activity.
Using accelerometers, researchers measured daily activity among 30 stroke survivors (mean age: 61.77 years) for a week. Stroke survivors completed the Short Physical Performance Battery (which measures balance, walking speed, and lower-limb endurance) and the Late-Life Function and Disability Instrument (which asks survivors to report on how difficult it is to do daily tasks). Using these tests, researchers assessed how much each survivor moved and how well they performed routine physical tasks. After controlling for age and time since stroke, they found that survivors who did a lot of light exercise—like taking leisurely walks, housekeeping, or light gardening—reported fewer physical limitations than less active survivors. On average, stroke survivors only did about 7 minutes of moderate-to-vigorous activity daily, compared with an average of over 3 hours of light exercise each day. Although the amount of moderate-to-vigorous exercise better predicted survivors’ performance on objective measures of physical function, their self-reported ability to carry out daily tasks was greatly associated with amount of time they spent in light physical activity. The bottom line is that, along with moderate-to-vigorous exercise, lighter tasks throughout the day can also go a long way in speeding up recovery in stroke survivors.
Concussions and brain deficits. Ever run a yellow light when it might’ve been safer to stop? (Don’t worry, we’re not judging.) Turns out, if you played a contact sport in your youth, the two may very well be connected. A new study links concussions to loss of inhibition.
Neuroscientists looked at the results of 12 cognitive tests from an online survey of about 20,000 people in the general population. Participants were asked about their concussion history, if they’d ever been knocked out, and, if so, the number of times. Those with a history of concussion did well on 11 of 12 cognitive tests, but showed a strong deficit when it came to the test of inhibitory control. The researchers then used those results to accurately predict the cognitive performance of 74 university football players. They did not request concussion history from the players before they completed the same cognitive tests. Football players did well on 11 of 12 cognitive tasks, but all players showed impairments in inhibitory control. Still, there is some good news. Despite poor performance on inhibition testing, people with a history of concussion had normal results when it came to memory and deductive reasoning, meaning that this type of injury doesn’t seem to have a huge impact on long-term cognition.
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Upcoming Medical Meetings
Please note that, in the interests of containing the current COVID-19 pandemic, the following meetings have been cancelled. Please contact these organizations for details and specifics on refunds and rescheduling:
15th Annual Brain Injury Rehabilitation Conference, to be held in San Diego, CA, May 8–9, 2020.
6th Annual Neuro and Intensive Care: Review, Workshops and Controversies 2020, to be held in Orlando, FL, May 7–9, 2020.
The following meetings have been rescheduled:
14th Annual Child Psychiatry in Primary Care Conference, to be held in Burlington, VT, May 8, 2020. Please check website for up-to-the-minute information.
Pediatric Epilepsy: New and Novel Approaches to Care, to be held in Southfield, MI, May 15–16, 2020, has been rescheduled for October 2–3, 2020, in Troy, MI.