Parkinson's: With work, there is hope after the diagnosis

James Neal | Enid News & Eagle  Dec 30, 2018  

Ronald Taylor

ENID, Okla. — When Ronald Taylor, 83, first started having trouble moving, he thought maybe he’d had a stroke. It turned out, he was suffering symptoms related to Parkinson’s disease, starting a long road in rehabilitation that’s led him back to mobility and self-sufficiency.

According to the Parkinson’s Foundation, about 60,000 Americans are diagnosed with Parkinson’s each year, and by 2020 almost one million Americans will be living with the disease.

Parkinson’s disease is a slowly-progressing neurodegenerative disease that causes tremors, limb rigidity, balance, gait and speech problems.

Ronald, who’s lived with his wife of 63 years, Shirley, in Enid since the couple came here with the Air Force in 1978, said he didn’t think something like Parkinson’s was possible for him.

But, gradually worsening problems getting in and out of his chair and walking came to a head in September when Shirley traveled to Dallas to visit their daughter.

Somehow, Shirley knew something was wrong with Ronald in her absence.

“The Lord woke me up that Saturday morning and said, ‘You need to go back to Enid,’” Shirley said.

She came back to Enid at about 6 p.m. the following day and found Ronald was nearly immobile in his chair.

Ronald had suffered a stroke two years earlier, and Shirley said she feared the outcome this time was going to be worse.

“I thought we were going to be making funeral arrangements,” Shirley said. “It was horrible.”

Ronald was rushed to the emergency room, where a stroke was ruled out. But, no other immediate causes were found for his trouble moving and his speech, which had dropped to a soft whisper.

“They couldn’t figure out anything that was wrong with him,” Shirley said.

After a neurologist was called in to consult on the case, it was determined Ronald was suffering from Parkinson’s symptoms.

“It was a shock, at first,” Ronald said. “As far as I was concerned I didn’t have anything like that. It was just old age taking its toll.”

Dr. Joseph Knapik, staff neurologist and director of inpatient rehabilitation at St. Mary’s Regional Medical Center, said Parkinson’s disease is caused by a deficiency in the brain of L-DOPA.

L-DOPA is an amino acid that plays a crucial role in the neurotransmitters dopamine, norepinephrine and epinephrine.

When not enough L-DOPA is present, disruptions in neurotransmissions cause resting tremors, lack of movement in parts of the body, a shuffling gait, balance problems, falls, slowing thought processes and speech disorders — particularly whispering speech.

In general, what causes Park­inson’s to develop remains somewhat of a mystery, Knapik said.

“We don’t fully understand all the genetics of this,” he said. “In general this is a sporadic disease. It tends to be seen in the older age population, but there is no specific reason we see they get this.”

He said it’s been hypothesized the brain loses the ability to develop L-DOPA as it ages, but that hasn’t been proven, nor is it understood why it presents in some older people and not others.

Parkinson’s typically shows up in patients in their 60s to 80s, Knapik said.

He said there is no blood test or imaging to detect Parkinson’s, and there are no known risk factors or preventive measures.

“There’s not a test to detect Parkinson’s,” Knapik said, “so usually neurologists are the ones involved in this and in taking care of these patients.”

In its earliest stages, Knapik said treatment involves adjusting the patient mentally and physically to life with Parkinson’s.

“Early on in the course it’s about educating the patient,” Knapik said, “and getting them to know what this really is.”

As the disorder progresses, Knapik said medications may be used to stimulate or supplement L-DOPA production in the brain. And finally, as physical symptoms worsen, intensive physical therapy is used to retrain the brain and body for movement and speech.

Ronald started that physical therapy while under inpatient care at St. Mary’s, after his initial diagnosis in September.

When he started out, he had to move with a walker, needed assistance getting out of a chair and had lost much of the dexterity in his hands. When he spoke at what he thought was a normal tone, others could barely hear him. If he spoke loud enough for others to hear him, he said it felt like he was shouting.

The physical therapy team got to work with him right away, in long courses of speech and motor exercises over two weeks. Walking, turning, getting out of a chair, getting dressed — it all had to be retrained.

Shirley said she had no doubt from the beginning Ronald would pull through it — with some divine help.

“God is bigger than any mountain we encounter,” Shirley said. “I know where my help comes from, and it comes from the Lord.”

Ronald drew on his old military discipline, and dug into the physical therapy with determination.

“I enjoyed it, I really did,” Ronald said. “I tried to make the best of it.”

After two weeks of rehabilitation at the hospital, Ronald was released for four weeks of outpatient rehab at St. Mary’s Center for Rehabilitation, 2123 W. Willow.

Nikki Haws, physical therapist assistant at St. Mary’s Center for Rehabilitation, said she was eager to work with Ronald after recently being certified in Lee Silverman Voice Treatment (LSVT) BIG, a program designed to improve gait, balance and motor skills in Parkinson’s patients.

“The treatment improves walking, self-care and other tasks by helping people ‘recalibrate’ how they perceive their movements with what others actually see,” according to the LSVT website. “It also teaches them how and when to apply extra effort to produce bigger motions – more like the movements of everyone around them.”

Haws said repetitive exercises help Parkinson’s patients break out of the narrowing confines of their disease.

“Their world has gotten small,” Haws said. “They have small movements and reduced speed, but they feel like they’re doing what they did 20 years ago.”

Through repetition, Haws said the exercises improve the brain’s neuroplasticity — the brain’s ability to “rewire” itself — and help patients “get comfortable outside that small world.”

Over four weeks, Haws worked Ronald through exercises focused on getting dressed, tying his own shoes and being able to get up from a chair or bed, then walking, turning and progressive exercises to improve gait and balance.

Haws said the LSVT program covers the spectrum of Parkinson’s patients from those who are just starting to have tremors to those already confined to a wheelchair. But, the earlier a patient starts, she said, the better.

“Early intervention with Parkinson’s is the best,” Haws said. “Let’s not wait until they’re having falls to get them help.”

Once physical therapy starts, there is no end point. Haws said, to be successful, a Parkinson’s patient will have to make a routine of exercises, twice a day every day, for the rest of their life.

Ronald said he’s committed to continuing that process, which already has brought from a walker and needing help dressing back to self-sufficiency.

“I really feel much better,” Ronald said, “and I’m really appreciative of everyone who was involved in it.”

In addition to their ongoing physical therapy, support also is available for Parkinson’s patients through the Parkinson Foundation of Oklahoma, which offers about 30 support groups around the state, including one which meets monthly in Enid.

Bruce McIntyre, Parkinson Foundation of Oklahoma executive director, said it’s important for Parkinson’s patients and their families to stay connected, educated and social.

“It’s very common when people are diagnosed, both as patients and as caregivers, they tend to withdraw and isolate themselves,” McIntyre said. “But, the connection with other people is very crucial, and can take them from a downward spiral to an upward spiral.”

Support groups offer a social network of friends, and also keep Parkinson’s patients and caregivers up-to-date on therapy options.

“The people who continue to learn with the disease tend to do better,” McIntyre said. “Learning about new options helps alleviate unnecessary fears.”

Parkinson Foundation of Oklahoma hosts a support group at 2 p.m. the first Friday of each month at Enid Senior Center, 202 W. Walnut.

For anyone who is experiencing symptoms they suspect may be related to Parkinson’s, Dr. Knapik advised they start by seeing their primary care physician.

And, for those who are diagnosed with Parkinson’s, Knapik said there is life and hope after the diagnosis.

“This a disease of decades,” Knapik said. “There are people who have been in my clinic for upwards of 20 years with this disease and they’re still up and going well.

“These are treatable diseases,” Knapik concluded. “There is management for this, both medicines and therapy, and we can help these people.”

Ronald Taylor does exercise with Kikki Haw, physical therapist assistant

https://www.enidnews.com/news/lifestyles/parkinson-s-with-work-there-is-hope-after-the-diagnosis/article_7b785a3e-140a-54b6-9ee0-d929ca3c5c75.html

Wireless 'pacemaker for the brain' could offer new treatment for neurological disorders

December 31, 2018, University of California - Berkeley

In a proposed device, two of the new chips would be embedded in a chassis located outside the head. Each chip could monitor electrical activity from 64 electrodes located into the brain while simultaneously delivering electrical stimulation to prevent unwanted seizures or tremors. Credit: Rikky Muller, UC Berkeley

A new neurostimulator developed by engineers at the University of California, Berkeley, can listen to and stimulate electric current in the brain at the same time, potentially delivering fine-tuned treatments to patients with diseases like epilepsy and Parkinson's.

The device, named the WAND, works like a "pacemaker for the brain," monitoring the brain's electrical activity and delivering electrical stimulation if it detects something amiss.

These devices can be extremely effective at preventing debilitating tremors or seizures in patients with a variety of neurological conditions. But the electrical signatures that precede a seizure or tremor can be extremely subtle, and the frequency and strength of electrical stimulation required to prevent them is equally touchy. It can take years of small adjustments by doctors before the devices provide optimal treatment.

WAND, which stands for wireless artifact-free neuromodulation device, is both wireless and autonomous, meaning that once it learns to recognize the signs of tremor or seizure, it can adjust the stimulation parameters on its own to prevent the unwanted movements. And because it is closed-loop—meaning it can stimulate and record simultaneously—it can adjust these parameters in real-time.

"The process of finding the right therapy for a patient is extremely costly and can take years. Significant reduction in both cost and duration can potentially lead to greatly improved outcomes and accessibility," said Rikky Muller assistant professor of electrical engineering and computer sciences at Berkeley. "We want to enable the device to figure out what is the best way to stimulate for a given patient to give the best outcomes. And you can only do that by listening and recording the neural signatures."

WAND can record electrical activity over 128 channels, or from 128 points in the brain, compared to eight channels in other closed-loop systems. To demonstrate the device, the team used WAND to recognize and delay specific arm movements in rhesus macaques. The device is described in a study that appeared today (Dec. 31) in Nature Biomedical Engineering.

WAND's custom integrated circuits. Credit: Rikky Muller, UC Berkeley

Ripples in a pond

Simultaneously stimulating and recording electrical signals in the brain is much like trying to see small ripples in a pond while also splashing your feet—the electrical signals from the brain are overwhelmed by the large pulses of electricity delivered by the stimulation.

Currently, deep brain stimulators either stop recording while delivering the electrical stimulation, or record at a different part of the brain from where the stimulation is applied—essentially measuring the small ripples at a different point in the pond from the splashing.

"In order to deliver closed-loop stimulation-based therapies, which is a big goal for people treating Parkinson's and epilepsy and a variety of neurological disorders, it is very important to both perform neural recordings and stimulation simultaneously, which currently no single commercial device does," said former UC Berkeley postdoctoral associate Samantha Santacruz, who is now an assistant professor at the University of Texas in Austin.

Researchers at Cortera Neurotechnologies, Inc., led by Rikky Muller, designed the WAND custom integrated circuits that can record the full signal from both the subtle brain waves and the strong electrical pulses. This chip design allows WAND to subtract the signal from the electrical pulses, resulting in a clean signal from the brain waves.

Existing devices are tuned to record signals only from the smaller brain waves and are overwhelmed by the large stimulation pulses, making this type of signal reconstruction impossible.

The WAND chip is designed with custom integrated circuits that can record the full signal from both subtle brain waves and strong electrical pulses delivered by the stimulator. Credit: Rikky Muller, UC Berkeley

"Because we can actually stimulate and record in the same brain region, we know exactly what is happening when we are providing a therapy," Muller said.

In collaboration with the lab of electrical engineering and computer science professor Jan Rabaey, the team built a platform device with wireless and closed-loop computational capabilities that can be programmed for use in a variety of research and clinical applications.

In experiments lead by Santacruz while a postdoc at UC Berkeley, and by and electrical engineering and computer science professor Jose Carmena, subjects were taught to use a joystick to move a cursor to a specific location. After a training period, the WAND device was capable of detecting the neural signatures that arose as the subjects prepared to perform the motion, and then deliver electrical stimulation that delayed the motion.

"While delaying reaction time is something that has been demonstrated before, this is, to our knowledge, the first time that it has been demonstrated in a closed-loop system based on a neurological recording only," Muller said.

"In the future we aim to incorporate learning into our closed-loop platform to build intelligent devices that can figure out how to best treat you, and remove the doctor from having to constantly intervene in this process," said Muller said.

More information: Andy Zhou et al, A wireless and artefact-free 128-channel neuromodulation device for closed-loop stimulation and recording in non-human primates, Nature Biomedical Engineering (2018).  DOI: 10.1038/s41551-018-0323-x 

Journal reference: Nature Biomedical Engineering 

Provided by: University of California - Berkeley 

https://medicalxpress.com/news/2018-12-wireless-pacemaker-brain-treatment-neurological.html

New optogenetic technique could help restore limb movement, treat muscle tremor

December 28, 2018 by Becky Ham, Massachusetts Institute of Technology

Shriya Srinivasan is a PhD student in medical engineering and medical physics at the MIT Media Lab and the Harvard-MIT Division of Health Sciences and Technology. Credit: James Day

For the first time, MIT researchers have shown that nerves made to express proteins that can be activated by light can produce limb movements that can be adjusted in real-time, using cues generated by the motion of the limb itself. The technique leads to movement that is smoother and less fatiguing than similar electrical systems that are sometimes used to stimulate nerves in spinal cord injury patients and others.

While this method was tested on animals, with further research and future trials in humans this optogenetic technique could be used someday to restore movement in patients with paralysis, or to treat unwanted movements such as muscle tremor in Parkinson's patients, said Shriya Srinivasan, a PhD student in medical engineering and medical physics at the MIT Media Lab and the Harvard-MIT Program in Health Sciences and Technology.

The first applications of the technology might be to restore motion to paralyzed limbs or to power prosthetics, but an optogenetic system has the potential to restore limb sensation, turn off unwanted pain signals or treat spastic or rigid muscle movements in neurological diseases such as amyotrophic lateral sclerosis or ALS, Srinivasan and her colleagues suggest.

The MIT team is one of very few research groups using optogenetics to control nerves outside the brain, Srinivasan said. "Most people are using optogenetics as sort of a tool to learn about neural circuits, but very few are looking at it as a clinically translatable therapeutic tool as we are."

"Artificial electrical stimulation of muscle often results in fatigue and poor controllability. In this study, we showed a mitigation of these common problems with optogenetic muscle control," said Hugh Herr, who led the research team and heads the Media Lab's Biomechatronics group. "This has great promise for the development of solutions for patients suffering from debilitating conditions like muscle paralysis."

The paper was published in the Dec. 13 issue of Nature Communications. The team included MIT researchers Benjamin E. Maimon, Maurizio Diaz, and Hyungeun Song.

Light versus electricity

Electrical stimulation of nerves is used clinically to treat breathing, bowel, bladder, and sexual dysfunction in spinal cord injury patients, as well as to improve muscle conditioning in people with muscular degenerative diseases. Electrical stimulation can also control paralyzed limbs and prosthetics. In all cases, electrical pulses delivered to nerve fibers called axons trigger movement in muscles activated by the fibers.

This type of electrical stimulation quickly fatigues muscles, can be painful, and is hard to target precisely, however, leading scientists like Srinivasan and Maimon to look for alternative methods of nerve stimulation.

Optogenetic stimulation relies on nerves that have been genetically engineered to express light-sensitive algae proteins called opsins. These proteins control electrical signals such as nerve impulses—essentially, turning them on and off—when they are exposed to certain wavelengths of light.

Using mice and rats engineered to express these opsins in two key nerves of the leg, the researchers were able to control the up and down movement of the rodents' ankle joint by switching on an LED that was either attached over the skin or implanted within the leg.

This is the first time that a "closed-loop" optogenetic system has been used to power a limb, the researchers said. Closed-loop systems change their stimulation in response to signals from the nerves they are activating, as opposed to "open-loop" systems that don't respond to feedback from the body.

In the case of the rodents, different cues including the angle of the ankle joint and changes in the length of the muscle fibers were the feedback used to control the ankle's motion. It's a system, said Srinivasan, "that in real time observes and minimizes the error between what we want to happen and what's really happening."

Stroll versus sprint

Optogenetic stimulation also led to less fatigue during cyclic motion than electrical stimulation, in a way that surprised the research team. In electrical systems, large-diameter axons are activated first, along with their large and oxygen-hungry muscles, before moving on to smaller axons and muscles. Optogenetic stimulation works in the opposite way, stimulating smaller axons before moving on to bigger fibers.

"When you're walking slowly, you're only activating those small fibers, but when you run a sprint, you're activating the big fibers," explained Srinivasan. "Electrical stimulation activates the big fibers first, so it's like you're walking but you're using all the energy it requires to do a sprint. It's quickly fatiguing because you're using way more horsepower than you need."

The scientists also noticed another curious pattern in the light stimulated system that was unlike electrical systems. "When we kept doing these experiments, especially for extended periods of time, we saw this really interesting behavior," Srinivasan said. "We're used to seeing systems perform really well, and then fatigue over time. But here we saw it perform really well, and then it fatigued, but if we kept going for longer the system recovered and started performing well again."

This unexpected rebound is related to how opsin activity cycles in the nerves, in a way that allows the full system to regenerate, the scientists concluded.

With less fatigue involved, the optogenetic system might be a good future fit for long-term motor operations such as robotic exoskeletons that allow some people with paralysis to walk, or as long-term rehabilitation tools for people with degenerative muscle diseases, Srinivasan suggested.

For the method to make the leap into humans, researchers need to experiment with the best ways to deliver light to nerves deep within the body, as well as find ways to express opsins in human nerves safely and efficiently.

"There are already some 300 trials using gene therapy, and a few trials that use opsins today, so it's likely in the foreseeable future," said Srinivasan. 

More information: Shriya S. Srinivasan et al. Closed-loop functional optogenetic stimulation, Nature Communications (2018). DOI: 10.1038/s41467-018-07721-w 

Journal reference: Nature Communications 

Provided by: Massachusetts Institute of Technology 

https://medicalxpress.com/news/2018-12-optogenetic-technique-limb-movement-muscle.html

How Exercise Reduces Belly Fat in Humans

NEUROSCIENCE NEWS   DECEMBER 27, 2018
Source: Cell Press.

According to researchers, interleukin 6 plays a critical role in how exercise helps to reduce body fat.

This graphical abstract shows that in abdominally obese people, exercise-mediated loss of visceral adipose tissue mass requires IL-6 receptor signaling. NeuroscienceNews.com image is credited to Wedell-Neergaard, Lehrskov, and Christensen, et al. / Cell Metabolism.

Some of you may have made a New Year’s resolution to hit the gym to tackle that annoying belly fat. But have you ever wondered how physical activity produces this desired effect? A signaling molecule called interleukin-6 plays a critical role in this process, researchers report December 27 in the journal Cell Metabolism.

As expected, a 12-week intervention consisting of bicycle exercise decreased visceral abdominal fat in obese adults. But remarkably, this effect was abolished in participants who were also treated with tocilizumab, a drug that blocks interleukin-6 signaling and is currently approved for the treatment of rheumatoid arthritis. Moreover, tocilizumab treatment increased cholesterol levels regardless of physical activity.

“The take home for the general audience is ‘do exercise,'” says first author Anne-Sophie Wedell-Neergaard of the University of Copenhagen. “We all know that exercise promotes better health, and now we also know that regular exercise training reduces abdominal fat mass and thereby potentially also the risk of developing cardio-metabolic diseases.”

Abdominal fat is associated with an increased risk of not only cardio-metabolic disease, but also cancer, dementia, and all-cause mortality. Physical activity reduces visceral fat tissue, which surrounds internal organs in the abdominal cavity, but the underlying mechanisms have not been clear. Some researchers have proposed that a “fight-or-flight” hormone called epinephrine mediates this effect. But Wedell-Neergaard and co-senior study author Helga Ellingsgaard of the University of Copenhagen suspected that interleukin-6 could also play an important role because it regulates energy metabolism, stimulates the breakdown of fats in healthy people, and is released from skeletal muscle during exercise.

To test this idea, the researchers carried out a 12-week, single-center trial in which they randomly assigned abdominally obese adults to four groups. A total of 53 participants received intravenous infusions of either tocilizumab or saline as a placebo every four weeks, combined with no exercise or a bicycle routine consisting of several 45-minute sessions each week. The researchers used magnetic resonance imaging to assess visceral fat tissue mass at the beginning and end of the study.

In the placebo groups, exercise reduced visceral fat tissue mass by an average of 225 grams, or 8 percent, compared with no exercise. But tocilizumab treatment eliminated this effect. In the exercise groups, tocilizumab also increased visceral fat tissue mass by approximately 278 grams compared with placebo. In addition, tocilizumab increased total cholesterol and “bad” low-density-lipoprotein (LDL) cholesterol compared with placebo, in both the exercise and no-exercise groups. “To our knowledge, this is the first study to show that interleukin-6 has a physiological role in regulating visceral fat mass in humans,” Wedell-Neergaard says.

The authors note that the study was exploratory and not intended to evaluate a given treatment in a clinical setting. To complicate matters, interleukin-6 can have seemingly opposite effects on inflammation, depending on the context. For example, chronic low-grade elevations of interleukin-6 are seen in patients with severe obesity, type 2 diabetes, and cardiovascular disease. “The signaling pathways in immune cells versus muscle cells differ substantially, resulting in pro-inflammatory and anti-inflammatory actions, so interleukin-6 may act differently in healthy and diseased people,” Wedell-Neergaard explains.

In future studies, the researchers will test the possibility that interleukin-6 affects whether fats or carbohydrates are used to generate energy under various conditions. They will also investigate whether more interleukin-6, potentially given as an injection, reduces visceral fat mass on its own. “We need a more in-depth understanding of this role of interleukin-6 in order to discuss its implications,” Wedell-Neergaard says.

In the meantime, the authors have some practical holiday exercise tips. “It is important to stress that when you start exercising, you may increase body weight due to increased muscle mass,” Wedell-Neergaard says. “So, in addition to measuring your overall body weight, it would be useful, and maybe more important, to measure waist circumference to keep track of the loss of visceral fat mass and to stay motivated.”

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: This study was funded by TrygFonden.

Source: Carly Britton – Cell Press

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is credited to Wedell-Neergaard, Lehrskov, and Christensen, et al. / Cell Metabolism.

Original Research: Abstract for “Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial” by Wedell-Neergaard, Lehrskov, and Christensen, et al. in Cell Metabolism. Published December 27 2018.

doi:10.1016/j.cmet.2018.12.007

Abstract

Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial

Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.

https://neurosciencenews.com/exercise-belly-fat-10391/

How lights could restore limb movement

December 27, 2018 By Danielle Kirsh

Researchers at Massachusetts Institute of Technology have used an optogenetic technique to create limb movement and treat muscle tremor in people who have had spinal cord injuries or neurological diseases.

The technique works by activating nerves that express proteins using light. It can be adjusted in real-time using motion cues from the limb. The researchers suggest that the technique could produce smoother limb movement than other electrical systems that are typically used to stimulate nerves in spinal cord injury patients.

This optogenetic technique has so far only been tested in animals, but the researchers suggest that it could be used to restore movement in patients with paralysis in the future. It could also treat unwanted movements that happen with Parkinson’s disease.

“Most people are using optogenetics as sort of a tool to learn about neural circuits, but very few are looking at it as a clinically translatable therapeutic tool as we are,” said Shriya Srinivasan, a researcher on the project, in a press release.

Applications for the technology include restoring motion in paralyzed limbs and powering prosthetics. Optogenetic systems can also restore limb sensation, turn off unwanted pain signals or treat spastic or rigid muscle movements from neurological diseases, according to the researchers.

“Artificial electrical stimulation of muscle often results in fatigue and poor controllability. In this study, we showed a mitigation of these common problems with optogenetic muscle control,” Hugh Herr, lead researchers, said. “This has great promise for the development of solutions for patients suffering from debilitating conditions like muscle paralysis.”

Electrical stimulation of nerves has been clinically used to treat treating, bowel, bladder and sexual dysfunction in spinal cord injury patients. It has also improved muscle conditioning in people who have muscular degenerative diseases and can control paralyzed limbs and prosthetics.

In typical electrical stimulation, electrical pulses are sent to nerve fibers called the axons where muscle movement is triggered by the fibers. This electrical stimulation can quickly fatigue muscles and can be painful, according to the researchers. It can also be hard to target precisely.

Optogenetic stimulation uses nerves that have been genetically engineered to express light-sensitive algae proteins known as opsin. The proteins are what controls electrical signals like nerve impulses. Exposing them to certain wavelengths of light can turn them on and off.

The researchers have engineered mice and rats to express opsins in the leg to control the up and down movement of the ankle joints when switching on an LED light attached over the skin or implanted in the leg.

The closed-loop system is able to change its stimulation in response to signals from the nerves they are activating. In the rodents, the different cues included the ankle joint angle and changes in the length of muscle fibers. The researchers say that the system observes and reduces error in real-time.

Tests of technique also showed that optogenetic stimulation could lead to less fatigue during cyclic motion when compared to electrical stimulation. Electrical systems have large-diameter axons that are activated first with large, oxygen-hungry muscles before smaller axons and muscles. Optogenetics works by stimulating smaller axons before moving on to the bigger fibers.

“When you’re walking slowly, you’re only activating those small fibers, but when you run a sprint, you’re activating the big fibers,” Srinivasan said. “Electrical stimulation activates the big fibers first, so it’s like you’re walking but you’re using all the energy it requires to do a sprint. It’s quickly fatiguing because you’re using way more horsepower than you need.”

The light stimulated system also had a different pattern than electrical systems.

“When we kept doing these experiments, especially for extended periods of time, we saw this really interesting behavior,” Srinivasan said. “We’re used to seeing systems perform really well, and then fatigue over time. But here we saw it perform really well, and then it fatigued, but if we kept going for longer, the system recovered and started performing well again.”

Opsin activity cycles in the nerves resulted in the unexpected rebound, allowing the system to regenerate, according to the researchers.

The researchers plan to test the system further to find the best ways to deliver light to nerves deep in the body while also finding ways to express opsin in human nerves safely and efficiently.

“There are already some 300 trials using gene therapy, and a few trials that use opsin today, so it’s likely in the foreseeable future,” Srinivasan said.

The study was published in the journal Nature Communications and was funded by the MIT Media Lab Consortium.

https://www.medicaldesignandoutsourcing.com/how-limb-movement-could-be-restored-using-light/

HomeFeatured: Your Brain Rewards You Twice Per Meal Neuroscience News

NEUROSCIENCE NEWS   DECEMBER 27, 20

Source: Cell Press.

Summary: Upon eating, dopamine is released in the brain at two different times, during ingestion and when the food reaches our stomach, researchers report.

Suppression of gut-induced release could potentially cause overeating of highly desired food items. NeuroscienceNews.com image is in the public domain.

We know a good meal can stimulate the release of the feel-good hormone dopamine, and now a study in humans from the Max Planck Institute for Metabolism Research in Germany suggests that dopamine release in the brain occurs at two different times: at the time the food is first ingested and another once the food reaches the stomach. The work appears December 27 in the journal Cell Metabolism.

“With the help of a new positron emission tomography (PET) technique we developed, we were not only able to find the two peaks of dopamine release, but we could also identify the specific brain regions that were associated with these releases,” says senior author Marc Tittgemeyer (@tittgemeyer), head of the Institute’s Translational Neurocircuitry Group.

 “While the first release occurred in brain regions associated with reward and sensory perception, the post-ingestive release involved additional regions related to higher cognitive functions.”

In the study, 12 healthy volunteers received either a palatable milkshake or a tasteless solution while PET data were recorded. Interestingly, the subjects’ craving or desire for the milkshake was proportionally linked to the amount of dopamine released in particular brain areas at the first tasting. But the higher the craving, the less delayed post-ingestive dopamine was released.

“On one hand, dopamine release mirrors our subjective desire to consume a food item. On the other hand, our desire seems to suppress gut-induced dopamine release,” says Heiko Backes, group leader for Multimodal Imaging of Brain Metabolism at the Institute, who is co-first author on the study with Sharmili Edwin Thanarajah.

Suppression of gut-induced release could potentially cause overeating of highly desired food items. “We continue to eat until sufficient dopamine was released,” Backes says but adds that this hypothesis remains to be tested in further studies.

Earlier experiments have demonstrated gut-induced dopamine release in mice, but this is the first time it has been shown in humans.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: This research was funded the German Research Foundation in the Transregional Collaborative Research Center and the German Centre for Diabetes Research.

Source: Carly Britton – Cell Press

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Abstract for “Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans” by Sharmili Edwin Thanarajah, Heiko Backes, Alexandra G. DiFeliceantonio, Kerstin Albus, Anna Lena Cremer, Ruth Hanssen, Rachel N. Lippert, Oliver A. Cornely, Dana M. Small, Jens C. Brüning, and Marc Tittgemeyer in Cell Metabolism. Published December 27 2018.

doi:10.1016/j.cmet.2018.12.006

Abstract

Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans

Pleasant taste and nutritional value guide food selection behavior. Here, orosensory features of food may be secondary to its nutritional value in underlying reinforcement, but it is unclear how the brain encodes the reward value of food. Orosensory and peripheral physiological signals may act together on dopaminergic circuits to drive food intake. We combined fMRI and a novel [11C]raclopride PET method to assess systems-level activation and dopamine release in response to palatable food intake in humans. We identified immediate orosensory and delayed post-ingestive dopamine release. Both responses recruit segregated brain regions: specialized integrative pathways and higher cognitive centers. Furthermore, we identified brain areas where dopamine release reflected the subjective desire to eat. Immediate dopamine release in these wanting-related regions was inversely correlated with, and presumably inhibited, post-ingestive release in the dorsal striatum. Our results highlight the role of brain and periphery in interacting to reinforce food intake in humans.

https://neurosciencenews.com/meal-brain-reward-10390/

Treatment of Parkinson's disease: Separating hope from hype

26-Dec-2018

The article by Dr. Alireza Mohammadi et al. is published in Current Gene Therapy, Volume 18, Issue 4, 2018

Bentham Science Publishers

Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor deficits majorly caused by the loss of dopaminergic cells in the Substantia Nigra pars compacta (SNc) as well as the destruction of nigrostriatal pathway. Despite the numerous advances in cutting-edge approaches for the treatment or prevention of PD, there still exists some obstacles that have incapacitated the definitive treatment of this disease. 

New therapeutic strategies have emerged over recent years to treat PD, including gene- and stem cell- based therapies, targeted delivery of neurotrophic factors, and brain stimulation techniques such as Transcranial Magnetic Stimulation (TMS), transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS). 

The review covers various gene therapy strategies including Adeno-Associated Virus-Glutamic Acid Decarboxylase (AAV-GAD), AAV-Aromatic L-Amino Acid Decarboxylase (AAV-AADC), Lenti-AADC/Tyrosine Hydroxylase/Guanosine Triphosphate- Cyclohydrolase I (Lenti-AADC/TH/GTP-CH1), AAV-Neurturin (AAV-NRTN), α-Synuclein silencing, and PRKN gene delivery. The review also covers the advantages and disadvantages of these treatments along with the results of relevant trials. With many advances in treatments for PD, there still exist some hurdles that have resulted in treatment failure; the reasons for failure of treatment were described, with hope separated from hype.

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Researchers at the Medical School explore novel ways to target Parkinson’s disease

By Nisha Dabhi | 12/27/2018

Team of researchers and clinicians examine the effects of using focused ultrasound technology as an alternative treatment for Parkinson’s disease

Team of researchers and clinicians examine the effects of using focused ultrasound technology as an alternative treatment for Parkinson’s disease

Researchers at the Medical School have found that using focused ultrasound technology — a non-invasive type of brain surgery — can reduce tremor symptoms in some Parkinson’s disease patients while also improving quality of life. 

Parkinson’s disease is a progressive neurological disorder that affects movement by impacting the dopamine-producing neurons in a part of the brain known as the substantia nigra. Dopamine is a neurotransmitter — a chemical substance transmitted from one neuron to another — that is known to be involved in movement.

The specific symptoms of this disorder vary from patient to patient. While some experience behavioral symptoms such as tremors, slowed movement, muscle rigidity and impaired balance, others also see changes in mood and cognition, especially in later stages of the disease when other brain pathways may be affected. 

Due to the heterogeneity of the disease, there is no single treatment, and its causes remain unknown. The fact that Parkinson’s disease affects the brain poses another challenge for researchers and clinicians regarding treatment. 

“Unlike things like kidney disease and liver disease, we can’t really take the brain out and put a new one back in,” said Binit Shah, a neurologist at the University Medical Center. “So, I think the amount that we can improve and learn is exponential.”

However, a number of treatments do exist and have been effective for a subset of Parkinson’s disease patients’ symptoms. According to Shah, one of the most conservative treatments — and one of the most important — is physical exercise and activity. 

With patients who have tremor symptoms related to the loss of dopamine-releasing neurons, the medication Levodopa  is used as a treatment, as it can be converted to dopamine and help with movement control. Although the medication can continue to remain effective for later stages of the disease, the disease progression may also develop other symptoms that the medication does not target.

“It may take more medication to get the same effect because the cells that make dopamine may not be functioning well or are degenerating, but also other features of PD can develop like problems with balance, swallowing, cognition, where the problem is not the lack of dopamine but is due to PD spreading to other parts of the brain,” Shah said. 

In cases where medication is not effective, deep brain stimulation, or DBS, has been used. DBS is an invasive procedure in which electrodes are implanted within certain areas of the brain and produce electrical impulses to disrupt irregular signaling. However, not all Parkinson’s patients are candidates for DBS, and some of those who are choose to opt out due to its invasiveness. 

Currently, a team of researchers and clinicians led by University neurosurgeon Jeff Elias — and including Shah and clinical neuropsychologist Scott Sperling — have pioneered the use of a new technology known as focused ultrasound to reduce tremor symptoms in Parkinson’s patients. 

In focused ultrasound, beams of ultrasound waves concentrate on a target with extreme precision and accuracy. This technology has been used to target tumors as well as open up the blood brain barrier — which prevents many treatments from entering the brain — so that medications can effectively enter and target areas in the brain. 

In the study, Parkinson’s disease patients were divided into two groups — one group received the focused ultrasound treatment, while the other did not receive this treatment. The focused ultrasound technology targeted the ventralis intermedius nucleus of the thalamus. 

“The thalamus is segmented into different areas, and one of those areas is a coordination [center] where a lot of motor fibers intercept and there are tremor fibers that can go through,” Shah said. 

While Elias administered the treatment, Shah did motor assessments in collaboration with other institutions without knowledge of the treatment the patient had received. The research found that there was significant reduction in tremor symptoms for the Parkinson’s disease patients who received focused ultrasound treatment. There was not a significant reduction in other symptoms, such as depression. 

At the same time, the researchers found that this focused ultrasound technology is safe and improves the quality of life for Parkinson’s patients. Sperling measured the quality of life of these patients who underwent the procedure over the span of a year. 

“What you do see is that individuals who had treatment had significant improvements in their quality of life, and if you track all the folks over the next years, you continue to see significant improvements in overall quality of life and in areas such as emotional wellbeing,” Sperling said. 

Now, the researchers and clinicians are looking into using focused ultrasound technology in other areas of the brain such as the subthalamic nucleus of the thalamus and the globus pallidus — both areas that research has shown to be potential targets for Parkinson’s disease. They hope to see if there are significant reductions in other motor symptoms as well as improvements in quality of life. 

Nevertheless, the complexity of the disease may continue to require that research produce new treatments for Parkinson’s disease. 

“These surgeries are new and not for everyone. It's important to note that with Parkinson’s disease there are a lot of effective treatments from [a] medication standpoint and DBS, which remains the primary neurosurgical treatment,” Sperling said. “But this is something that is new and could be [an option] for certain individuals but are not standard practice for everyone with Parkinson’s disease.”

http://www.cavalierdaily.com/article/2018/12/researchers-at-the-medical-school-explore-novel-ways-to-target-parkinsons-disease