Study reveals inaccurate label claims on unregulated CBD products

Study reveals inaccurate label claims on unregulated CBD products

Recent studies have highlighted the therapeutic benefits of cannabidiol (CBD), which is a non-intoxicating component of Cannabis sativa. Previously, the association of Δ9-tetrahydrocannabinol (Δ9-THC) with CBD limited studies on its medicinal benefits.

The Agricultural Improvement Act of 2018 (2018 Farm Bill) legalized the use of products from the plant parts of Cannabis sativa, which is also known as hemp. This led to the rapid growth of the CBD industry.

Background

In June 2018, a purified oral solution of CBD known as Epidolex® received approval by the United States Food and Drug Administration (FDA) for the treatment of three forms of epilepsy.

However, except for Epidolex®, other CBD products remain unregulated in the U.S. In June 2019, the FDA held a general public hearing to hear concerns from scientists regarding CBD regulation.

Many research groups, along with the FDA, have identified numerous issues with label accuracy for several CBD products. This issue was not restricted to the U.S., as similar reports have also been published in the Netherlands, United Kingdom, and Italy.

A new Journal of Cannabis Research study aimed to determine the CBD content in various products and compare it to their label claims. The products assessed in this study were purchased from several stores in Central Kentucky, as well as online retailers, between April 2, 2021, and May 9, 2021.

About the study

The current study involved a total of 80 samples, 44 of which were purchased from online retailers that were U.S.-based. The remaining 36 samples were purchased from local retailers within Central Kentucky.

Taken together, the samples included in this study were produced by 51 different brands. Epidiolex® was also used as a positive control. All CBD products were tested immediately upon opening and before their expiration dates.

To determine label accuracy, a ±10% of the allowable variance was used. The products with CBD concentration exceeding 110% of the labeled value were considered under-labeled, while those with less than 90% of their labeled CBD content were considered over-labeled. Products with a CBD concentration that was between 90-110% of their labeled CBD content were considered to be accurately labeled.

Thereafter, all samples were prepared and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Study findings

Out of the 80 tested samples, 31% were under-labeled, 54% were labeled accurately, and 15% were over-labeled. Out of the 44 products that were purchased online, 25% were under-labeled, 61% were labeled accurately, and 14% were over-labeled. For the 36 products that were purchased locally, 39% were under-labeled, 17% were over-labeled, and 44% were labeled accurately.

The CBD concentrations ranged from 2.9 to 61.3 mg/mL for all unregulated samples, with labeled CBD concentrations ranging from 17-159%. The average amount of CBD for under-labeled products was 121% of the label claim, as compared to 61% in over-labeled products.

Conclusions

The current study provides evidence that CBD products from several countries around the world often had inconsistent CBD concentrations with their label claims. Such inaccurate labelings can pose safety risks to consumers who use CBD products for medical treatments.

Thus, clear regulations from both the federal and state agencies, as well as good manufacturing practices, are required to guarantee that the label claims of CBD products are accurate.

Limitations

The study has certain limitations. First, the study included only hemp-derived oil products. Second, only CBD concentrations were reported, while other cannabinoid concentrations were not reported. The current study also did not involve a formal sampling protocol.

 

Source: news-medical.net, Suchandrima Bhowmik

Epilepsy: How Ginger Boosts Effectiveness Of Medicine

Epilepsy: How Ginger Boosts Effectiveness Of Medicine

GINGER is used in Nigerian folk medicine to manage colds, pain, arthritis, vomiting and nausea. Beyond all these, ginger has promising benefits that may reduce cognitive deficits, brain cell loss, and seizure severity in individuals with epilepsy.

In a new study, researchers said that ginger may be used as supplements to antiepileptic drugs to potentiate their effectiveness with tolerable side effects. Ginger alone did not affect seizure severity but as a supplement with Sodium Valproate, an antiepileptic drug, it can significantly improve learning performance and protect against brain cell loss.

Epilepsy is a neurological disorder that affects people of all ages. According to World Health Organization, globally about 2.4 million people are diagnosed with epilepsy annually. This debilitating neurological disorder is often accompanied by cognitive deficits affecting attention, language, memory, and executive functions and adversely affects the quality of life of the patients and their families.

Although epilepsy is a treatable condition, over 75% of the patients from low-income populations around the world do not receive any treatment. Therefore, new antiepileptic medications with high efficacy and a more tolerable side-effect profile need to be developed and made available in low-income countries.

Recent preclinical studies showed that ginger extract might also be useful in the treatment of Alzheimer’s disease and cognitive impairment. The chemical constituents of ginger, specifically, [6]-gingerol, [8]-gingerol, and [6]-shogaol can penetrate the blood-brain barrier, suggesting that these substances might contribute to the effects of ginger extracts on the central nervous system.

The researchers had determined whether chronic administration of aqueous extract of ginger alone (GE) or in combination with SDV can ameliorate seizure severity, cognitive impairments, and brain cell loss in animal models with epilepsy.

These male mice were pretreated with ginger extract, Sodium Valproate (100 and 200 mg/kg), and a mixture of ginger extract and Sodium Valproate. Control animals received the same number of saline solution injections.

Afterwards, the mice underwent a learning performance test. Their brains were also excised and the hippocampi isolated from them for studies. It was in the journal, OBM Integrative and Complementary Medicine

Pretreatment with sodium valproate at 100 and 200 mg/kg significantly reduced the seizure severity score compared to what occurred in the control group that had a salt solution. Ginger extract alone did not affect kindled seizures.

However, the co-administration of ginger extract with sodium valproate did not significantly enhance the effect of sodium valproate in reducing the seizure severity score, suggesting that the treatment only caused a gradual increase in brain excitability.

The researchers said that although the combination of ginger extract and sodium valproate reduced the anticonvulsant activity of sodium valproate, it significantly counteracted learning deficits in epilepsy animal models.

However, they said that subsequent studies should consider the effect of ginger extract in combination with sodium valproate and other antiepileptic drugs in preventing epileptic attacks and anti-inflammatory actions.

Previous studies have identified local herbs and spices that could be used to effectively manage neurological disorders like convulsion, epilepsy and seizures. The local plants include Tetrapleura tetraptera, cowhage, cloves, turmeric, thyme, and Cannabis sativa.

Tetrapleura tetraptera is locally known as aridan among the Yoruba, osakirisa or oshosho among the Igbo, dawo among the Hausa, all in Nigeria. Commonly called Velvet bean or Cowhage, Mucuna pruriens is known as werepe in Yoruba and agbala or agbaloko in Ibo.

Turmeric is a spice that comes from the root of Curcuma longa, a member of the ginger family, Zingaberaceae. In Nigeria, it is called atale pupa in Yoruba; gangamau in Hausa; nwandumo in Ebonyi; ohu boboch in Enugu (Nkanu East);  and onjonigho in Cross River (Meo tribe).

Commonly called clove, Syzygium aromaticum belongs to the plant family Myrtaceae. The locals, especially in Lagos call it konofo.

Results of a study published in Phytotherapy Research concluded: “Tetrapleura tetraptera fruit aqueous extract (TTE) possesses analgesic and anticonvulsant properties. These findings lend pharmacological support to the suggested folkloric uses of the plant’s fruit in the management and/or control of painful, arthritic inflammatory conditions, as well as for the management and/or control of epilepsy and childhood convulsions in some tropical African countries.”

Also, extracts of cloves have been used to treat convulsion, seizures and sleeplessness in a study published in the Nigerian Journal of Pharmaceutical Sciences. According to the study, “The result of this study, therefore, suggests that the ethyl acetate fraction may not have contained the bioactive constituents that are useful in the treatment of epilepsy. However, the fraction may contain constituents that are beneficial in potentiating the effects of diazepam in inducing sleep suggesting sedative activity of the fraction.”

 

Source: tribuneonlineng.com, Sade Oguntola

CBD could treat seizures in both humans and dogs

CBD could treat seizures in both humans and dogs

A study found 90% of dogs who received CBD oil experienced a reduction in the frequency of seizures.

CBD, short for cannabidiol, is one of the hundreds of chemical compounds naturally found in marijuana. Unlike THC, however, CBD is non-psychoactive, meaning it doesn’t produce a high — which makes it much more appealing for medical purposes.

Research suggests CBD may help reduce pain and anxiety, as well as prevent some types of seizures, including Lennox-Gastaut, Dravet syndrome, or tuberous sclerosis complex. But it’s not only humans that can benefit from the anti-seizure properties of CBD; recent research is suggesting that cannabinoids may also be effective at reducing the frequency of seizures in dogs.

Canine idiopathic epilepsy, which occurs with no known cause, affects up to 6% of the pet dog population worldwide, making it the most common canine neurologic condition. This condition is much more common among purebred dogs versus mixed breed dogs and affects males more frequently than females.

Just like humans, seizures in dogs manifest themselves through stiffening and paddling movements, along with the loss of consciousness. In between the seizure episodes, the dog is perfectly normal from a neurological point of view.

Typically, drugs like phenobarbital and potassium bromide are used to treat epileptic dogs, with about 60-70% achieving good seizure control. However, many dogs still don’t respond well to treatment, risking euthanasia due to the poor quality of life for the dogs and their owners.

Researchers led by Dr. Stephanie McGrath at Colorado State University wanted to investigate alternatives to conventional treatments. Inspired by promising research on humans with epilepsy treated with CBD, the researchers embarked on a small trial with 16 pet dogs with epilepsy.

The dogs were assigned randomly to either the treatment or placebo group, with those in the former group receiving CBD oil for 12 weeks. All of the dogs were required to stay on the standard anticonvulsant drugs, including phenobarbital and potassium bromide, as denying them their treatment would have been unethical. The dog owners themselves did not know whether their dogs received CBD or a placebo.

According to the results, about 90% of dogs who received CBD experienced a reduction in the frequency of seizures, the researchers reported in the Journal of the American Veterinary Medical Association. The degree of seizure reduction was linked to the CBD concentration in the canines’ blood.

“We saw a correlation between how high the levels of CBD were in these dogs with how great the seizure reduction was,” McGrath said in a statement.

But despite the promising results, McGrath is cautious as the study’s sample size is so small. She is planning to conduct more research with a lot more dogs and hopes that CBD could be shown to be a good alternative to anticonvulsant drugs. In the meantime, when asked whether pet owners and veterinarians should give CBD to epileptic dogs, McGrath said:

“If you want to try it, it probably won’t hurt,” McGrath says. “But do we know it will help? We don’t.”

The market is already pretty rich with CBD products marketed for pets, including CBD oil for cats. However, pet owners should not medicate their epileptic dogs solely with CBD. Until further research proves its anti-convulsive effects, you should use the marijuana extract in conjunction with standard treatment. Hopefully, new research will come out more conclusive as some dogs desperately need treatment.

“I see a lot of epileptic patients,” McGrath. “It’s a very heart-wrenching disease. It’s very hard to watch dogs have seizures. It’s very hard to coach owners through the process. It’s very traumatic.”

 

Source: zmescience.com, Tibi Puiu

First look at a small protein’s structure could advance treatments for epilepsy and other disorders

First look at a small protein’s structure could advance treatments for epilepsy and other disorders

Findings by scientists at USC Dornsife using cryogenic electron microscopy could lead to answers for neurological disorders from anxiety to schizophrenia and Parkinson’s disease to autism spectrum disorder.

In brief:

  • Scientists at USC Dornsife have, for the first time, determined the structure of a key protein that transports a neurotransmitter responsible for reducing the activity of neurons in the brain, providing details at the atomic level.
  • The discovery, made using the relatively new and highly advanced technique of cryogenic electron microscopy (cryo-EM), could lead to new therapies for a range of neurological disorders, including epilepsy, anxiety, schizophrenia, Parkinson’s disease and autism spectrum disorder.
  • The protein is one of the smallest ever to have its structure determined using cryo-EM.

Scientists have, for the first time, revealed at the atomic level the structure of a protein that carries one of the body’s most important neurotransmitters into neurons.

In determining the structure of this transporter protein — one of the smallest proteins ever resolved — the researchers open new avenues to improve drugs for a wide range of debilitating conditions, including epilepsy, bipolar disorder, schizophrenia, Parkinson’s and Huntington’s diseases, anxiety and autism spectrum disorder.

The study was published June 8 in the journal Nature.

Neurons relay signals to one another by sending neurotransmitters across gaps between them, called synapses. The molecule GABA (short for gamma-amino butyric acid) is one of the most prevalent neurotransmitters in the brain.

When one neuron emits GABA, sending it out across a synapse toward a nearby neuron, GABA inhibits the activity of the receiving neuron.

But sometimes conditions can go awry, and not enough GABA reaches the receiving neuron, which may then become overactive, sending too many electrical impulses. This can cause a number of debilitating effects, including seizures.

Fortunately, certain drugs can help by blocking a protein called GAT-1 (short for GABA transporter 1). GAT-1 is responsible for recycling released GABA back into the emitting neuron.

Once such GAT-1 inhibitor, tiagabine (brand name Gabitril), reduces GABA recycling, leaving more GABA in the synapse to reduce the receiving neuron’s activity.

Although tiagabine can be effective, the exact way it interacts with GAT-1 to inhibit GABA recycling has been a mystery. And knowing how they interact could help researchers one day make more effective drugs.

To solve the mystery and see exactly how tiagabine binds to GAT-1, researchers at the USC Dornsife College of Letters, Arts and Sciences used highly advanced cryogenic electron microscopy, commonly known as cryo-EM. The technique involves freezing molecules at extremely low temperatures, near to where atoms and molecules stop moving altogether, and then imaging them with an electron microscope.

USC recently unveiled its new cryo-EM facility in the Core Center of Excellence in Nano Imaging at the USC Michelson Center for Convergent Bioscience.

Cornelius Gati, lead author on the study, and a team of USC Dornsife scientists observed GAT-1 in complex with tiagabine and used cryo-EM to visualize how the two interact.

“Previous understanding of the inhibitor (tiagabine) was purely based on biochemical studies, which do not provide any details at the atomic scale,” said Gati, assistant professor of biological sciences and chemistry at USC Dornsife. “We can now pinpoint specific parts of the drug that interact with the protein.”

Gati said this new insight suggests a previously unknown mechanism of inhibiting GAT-1 that involves a change in the protein’s overall shape when tiagabine binds to it.

The highly detailed information revealed by the study could help researchers improve drugs or develop new therapies for treating diseases related to GABA-controlled neurons.

“These findings have direct implications on pharmacology as a whole, not only with respect to treating epilepsy, but many other diseases,” Gati said, adding that the results point to further avenues of research.

“We have a feeling that this newly revealed mechanism is much more common than is currently thought, so we will investigate this first by using structurally similar inhibitors, and then expand our search to other molecules.”

Gati also noted that resolving the structure of the interacting molecules using cryo-EM proved extremely challenging — GAT-1 is one of the smallest proteins resolved with the technique, making it difficult to visualize even with such advanced technology.

Their success, he said, will motivate scientists at USC and other institutions to determine the structure of other challenging membrane proteins, leading to further understanding of drug-protein interaction and improved therapeutics.

 

Source: dornsife.usc.edu,  Darrin S. Joy

Epileptic mum accused of being drunk and targeted by thieves while having seizure in street

Epileptic mum accused of being drunk and targeted by thieves while having seizure in street

Rhiain Mort said she has received “nasty comments” and abuse from people

A mum who has neurological condition said she has been accused of “faking it” or being drunk.

Rhiain Mort, from Bootle, was diagnosed with epilepsy 13 years ago, when her son was four. Since then, it has affected her memory and her seizures meant she had to stop working. More than anything, it has affected her mental health.

The 37-year-old said she suffers “extreme anxiety” about being alone and has received “nasty comments” when she has had a seizure in public. Rhiain said: “I experience such extreme anxiety about being out alone and so vulnerable based on previous experiences.

“I have been subjected to nasty comments and abusive behaviours when I have had seizures in public, people have even accused me of faking it, or being drunk. Someone once even stole my purse when I was having a seizure on the floor.

“The epilepsy is just one thing. But everything that goes with it can feel like I’m suffocating under stress and anxiety and it can feel difficult to face each day. I feel incredibly isolated as I’ve found that people stop calling and inviting you out after that time you had a seizure and ruined everyone’s experience.

“Thankfully I have a very supportive partner and son. And a few very good friends who lift my spirits on darker days. I have not seen an epilepsy specialist face-to-face for four years. I wish people understood how lonely and terrifying it feels to live in a body that betrays you and makes you feel like a burden to others.”

The mum is now backing a nationwide campaign to call for the transformation of neurological services, as a new landmark survey has found nearly 67% people with a neurological condition are not having their mental wellbeing needs sufficiently met.

Rhiain has joined Neurological Alliance’s across the UK, which together represent more than 100 organisations including organisations such as the MS Society and Epilepsy Acton, to speak out about how the lack of mental health support can make a neurological condition significantly worse, and leave people feeling isolated and withdrawn from social relationships and work.

Results from the My Neuro Survey – which asked 8,500 people living with neurological conditions about their experiences accessing treatment, care and support – revealed the vast majority said their condition had made their mental wellbeing worse. Despite the best efforts of services and healthcare professionals across the country, over half said they hadn’t been asked about their mental wellbeing by a healthcare professional in the past three years, according to The Neurological Alliance.

Due to staff shortages, poor integration of physical and mental wellbeing and restrictive and inconsistent commissioning of services, thousands of people are facing a daily battle with the healthcare system, including long waits for care. The report also highlights concerning delays to treatment and care reported in the survey, with more than half of adults experiencing delays to a routine neurologist appointment.

As part of the #BackThe1in6 campaign, people across the UK are being urged to sign a petition to all UK Health Ministers, calling on them to work together through a Neuro Taskforce to set out their plans to improve treatment, care and support for people affected by neurological conditions. The Neuro Taskforce would bring together relevant departments, health and social care bodies, professional bodies, people affected by neurological conditions and the voluntary sector in all four UK nations.

Georgina Carr, Chief Executive at the Neurological Alliance, says: “Living with a neurological condition can be exhausting and scary, and can have an enormous impact on mental health. Yet our report reveals people, like Rhiain are being left to struggle on alone – either not knowing where to go to for support, or facing an uphill battle to access under-resourced healthcare professionals.

“For years, people with neurological conditions have felt ignored, with public policy and service improvement for neuroscience under-prioritised. The tide is starting to turn, but we now need all four Governments to work together to develop and resource clear plans to improve the lives of the one in six people in the UK who live with a neurological condition. They must urgently put together a Neuro Taskforce to make sure we have the right services in place for people with a neurological condition now and in the future.

“With NHS England and Improvement recently announcing Integrated Care Systems are ‘ready to take on much greater responsibility’ – which will include more specialised services that people with neurological conditions rely on – the experiences that underpin the report and our calls to action must be heard now. Everyone living with a neurological condition must have access to high quality, joined up neurological care, wherever they live.”

 

Source: liverpoolecho.co.uk, Olivia Williams

Teaching Teachers About Epilepsy: Intervention Also Benefits Students, Parents, Neurologists

Teaching Teachers About Epilepsy: Intervention Also Benefits Students, Parents, Neurologists

In Ontario, Canada, a group of psychologists and members of a community epilepsy support agency had long discussed the need for epilepsy education for schoolteacher’s.

“We’ve found that teachers don’t have knowledge of epilepsy, and many are afraid of having children with epilepsy in their classroom because they feel overwhelmed by the possibilities,” said Mary Lou Smith, professor and neuropsychologist at the University of Toronto. “This fear and lack of knowledge act as additional barriers to effective instruction and inclusion.”

A 2015 study by the US Centers for Disease Control and Prevention used survey data from more than 32,000 students with special health care needs. The study found that compared with students with other health care needs, students with epilepsy were twice as likely to miss at least 11 days of school during an academic year, and had greater needs for special education services and communication services.

Schools can be an important focus for screening of children for epilepsy, as well as educational efforts to address basic knowledge, stigma, and misconceptions associated with epilepsy. Schools also are an appropriate and necessary place to provide seizure first aid to affected students, teachers, and staff, as well as rescue medications when needed.

While 14 US states and at least one Australian state have “seizure-safe schools” laws that require some level of teacher training, most countries have no requirement that teachers learn about epilepsy or how to handle seizures in students.

Developing effective materials: Focus group

Through focus groups with teachers, the Ontario researchers developed a 10-minute video, as well as a video on rescue medication and downloadable booklets.

The researchers selected a 10-member group consisting of teachers, principals, other staff, and the parent of a student with epilepsy. This group participated in a two-hour codesign workshop meant to establish how to develop the training materials.

“We knew when we brought these people together, we were going to listen to what they said and create a resource that they would use, because it had components that mattered to them,” said Mary Secco, speaking in a “making of” video that explains how the workshop was run and how the materials were created.

The researchers had envisioned a 45- to 60-minute video as part of the training. “The teachers said no, we’re overwhelmed with work and educational requirements – there is no way we would watch something that long,” said Dr. Smith.

During the workshop, the researchers showed multiple videos and other materials to the group and asked for specific feedback about what was effective.

Drawing on the expertise of the neuropsychologists on the team, the materials also include information on how the brain works and how teachers can support students in the social, psychological, and cognitive consequences of epilepsy. That information was shared with the focus group at the end of the workshop.

Study: Video improves knowledge, reduces uncertainty

The 10-minute video was shown to a group of 90 teacher trainees at Western University in London, Ontario. Of these, 57 completed pre- and post-video questionnaires about their knowledge and understanding of epilepsy. The post-video questionnaire also asked respondents for feedback on the video.

The analysis of the results, published in 2021, found that teachers exhibited limited knowledge of epilepsy and seizures before the training, with only 60% scoring above 50% on the pre-training questionnaire. Before the training, 68% of participants believed that epilepsy had no cognitive consequences and 74% felt unprepared to handle a seizure in a student.

Scores increased significantly after the video was shown, with overall accuracy scores increasing from 59% to 75%. In the post-video survey, 75% of respondents said the video was adequate or excellent as an educational tool. And 79% of those who had said they felt unprepared to handle a seizure now felt prepared.

Because most schools in Canada do not employ school nurses, Dr. Smith said the program also may reduce calls to emergency services. “We get many cases where teachers or principals will call 911 when a child has a seizure even though it’s not necessary,” she said. “It’s because they don’t have the knowledge—they don’t have someone to step up and say, ‘We can manage this here.’”

Helping students, helping families

Jennifer Garner was introduced to the online training materials while participating in a research study at Sick Kids Children’s Hospital in Toronto. “I was talking with them about how I struggle talking with the school about all of the consequences of my daughter’s epilepsy, not just the seizures,” she said. “And they shared the teacher toolkit with me.”

Garner’s daughter Julia was diagnosed with juvenile myoclonic epilepsy in late 2019, when she was in eighth grade.

More than 30 years before, Garner had received the same diagnosis at the same age. “In one sense, Julia is lucky because I understand what she is going through and I can explain things from my perspective,” she said.

Garner has shared the toolkit with Julia’s teachers. “They found it all so helpful, especially during COVID when learning was happening so differently,” she said.

“I knew her teachers were medically able to take care of Julia if something happened,” said Garner. “But there’s an emotional part to it, how to help when someone is coming out of a seizure. Your brain isn’t quite functioning; you know you’ve had a seizure, but you don’t fully understand what’s going on.”

The toolkit also covers learning, memory, and social challenges that can occur in children with epilepsy, which helped Garner and the teachers understand Julia’s challenges and how to help.

“I wish I had these materials years ago”

Garner also shared the materials with her sister, also a teacher. “She said it opened her eyes to the fact that things aren’t always what they seem,” she said. “It helped her look beyond the simplest explanation of what might be going on with a student.”

The toolkit helped Garner, as well, to understand her daughter’s academic challenges and behavior. “I wish I’d had these materials years ago,” she said, “both for her sake and for my own understanding of myself.”

Now that the materials are publicly available, Dr. Smith and colleagues hope to spread the word about the training. “Our hope would be that once teachers watch this video, they can revisit it later, particularly if they have a student with epilepsy in their classroom,” she said.

 

Source: newswise.com, International League Against Epilepsy

Changing Minds

Changing Minds

UC Davis researchers are bringing the benefits of drugs like LSD and cannabis to light. They may be the next big thing in pharmaceuticals for treating a range of problems like depression and anxiety.

For decades, possession and use of drugs like LSD and cannabis has come with a threat of prosecution and jail time. But in the past few years, researchers have started taking a closer look at these compounds, finding potential for new treatments for psychiatric and central nervous system problems such as seizures, depression, anxiety and post-traumatic stress disorder. UC Davis scientists are among the small group of licensed researchers pushing the field forward — including launching startup companies to help bring these new drugs to market. 

The need for new drugs

Mental health disorders are very common. About 1 in 5 Americans live with some form of mental illness, according to the National Institute of Mental Health. 

Drugs are available to help these patients, said Cameron Carter, distinguished professor in the UC Davis Department of Psychiatry and Behavioral Sciences, and Center for Neuroscience. “We have a repertoire of effective treatments that we didn’t have 30 or 40 years ago.”

At the same time, existing drugs have drawbacks, Carter said. They are slow-acting, taking days or weeks to show effect. Not all patients respond to current treatments, and they are based on a limited understanding of the root causes of mental illness.

UC Davis associate professor in chemistry David Olson became interested in psychedelic drugs for psychiatric treatment as a postdoctoral researcher at the Broad Institute in Cambridge, Massachusetts. 

At the time, a lot of research focused on ketamine, Olson said. Ketamine is used as an anesthetic and also abused as a recreational drug. But it also turns out to be a remarkably effective antidepressant. Ketamine acts within hours, and the effect of a single treatment can last for up to a week, Olson said. It works across a range of indications including depression, PTSD and substance abuse. 

In 2019, the U.S. Food and Drug Administration approved esketamine, a version of the drug delivered as a nasal spray, for treatment of severe, treatment-resistant depression. The treatment has to be given in a clinical setting, where the patient is monitored for several hours. 

A common feature of disorders such as depression, anxiety and PTSD is atrophy, or withering of neurons in the prefrontal cortex. Ketamine appears to act by reversing this atrophy and repairing neural connections in the brain.

Olson wondered if there might be other molecules with a similar effect and started to look at psychedelics such as LSD, MDMA and DMT (the active component in the herbal drug ayahuasca). 

Olson joined the UC Davis faculty in 2015, and in 2018, his group published papers showing that a wide variety of psychedelics could cause nerve cells to form new connections and that they could help rodents overcome “fear responses” — a model for anxiety and PTSD. 

Olson named this class of drugs “psychoplastogens” because they encourage neural plasticity, or the regrowth of structures that make connections between neurons. 

A healing-based approach

Recently published results show that MDMA and psilocybin, in combination with psychotherapy, are effective in treating PTSD and depression. Olson said that one or more of these drugs — still widely illegal — could soon be approved for clinical use. 

But major barriers to psychedelics in clinical use still exist. The possibility of hallucinogenic side effects, and the stigma of illegality, could put off both physicians and patients. More significantly, psychedelic therapy is usually accompanied by psychotherapy before and after drug treatment, and the patient needs to be monitored during their trip. That makes treatment expensive compared to a daily or weekly pill you can keep in the bathroom cabinet. 

“Scalability is a huge issue for psychedelics,” Olson said. “A big goal of mine is to produce medicines that are accessible to everyone.” 

Olson’s laboratory aims to separate the ability to repair damaged neural connections in the brain from the psychedelic properties of these drugs. The goal is a drug that is fast-acting with a lasting effect from a single dose and does not cause side effects such as hallucinations. 

To achieve this, they take the chemical structures of known psychedelic drugs and alter them to come up with new candidates that can be tested for their psychoplastogenic properties in cell cultures and animal models. 

Ibogaine, for example, is a psychedelic drug extracted from the iboga tree, Tabernanthe iboga. Ibogaine is reputed to be effective in treating addiction, but it also causes hallucinations and heart problems.

Olson’s laboratory synthesized a number of compounds similar in structure to ibogaine and came up with one they called tabernanthalog, or TBG. Similar to other psychoplastogens like ketamine, LSD and MDMA, tabernanthalog promoted growth of branches and spines in rat nerve cells, and showed positive effects in animal models of depression and addiction. It did not have negative effects on the heart like ibogaine, and it did not cause a “head twitch” response in mice, considered to be a marker for hallucinations in humans. The work was published in Nature in 2021.

In 2019, Olson founded a startup company, Delix Therapeutics Inc., to help develop these promising drug candidates and bring them to market. So far, Delix has raised about $100 million in funding and plans to bring two compounds into phase 1 clinical trials sometime this year.

“I’m so excited about this class of molecules,” Olson said. While currently approved drugs treat the symptoms of mental illness, Olson believes that psychoplastogens have the potential to restore the prefrontal cortex, a key region of the brain involved in motivation, cognition and decision-making in the human brain.

“It’s a paradigm shift to a healing-based approach,” he said.

Speeding drug development

One problem with developing new drugs based on psychedelics is how to screen out those that cause hallucinations before they get to human trials. The rodent head twitch test is considered to be a reliable predictor, but you can’t really ask a mouse if it’s hallucinating. This presents a bottleneck for developing new drugs.

“We don’t have good ways to screen neurological drugs at scale,” said Lin Tian, professor of biochemistry and molecular medicine in the UC Davis School of Medicine. Tests that could be carried out in cell culture would allow for more rapid screening.

Tian’s lab uses light-based technology to study the chemical messengers and receptors that carry signals in the brain. After Olson gave a departmental seminar on drugs affecting the serotonin 2A receptor, the two laboratories began collaborating.

Graduate students Jason Dong, Calvin Ly and Lee Dunlap came up with psychLight, a modified version of the serotonin 2A, or 5-HT2A, receptor with a fluorescent tag. When psychLight is engaged by a hallucinogenic drug it changes shape slightly, causing its fluorescence to increase. Non-hallucinogenic compounds binding to psychLight cause a different fluorescence profile.

PsychLight can be used to rapidly screen large numbers of candidate molecules for potential to cause hallucinations, in biochemical assays or in cell cultures. This approach can also be used to carry out basic research on brain signaling, which is fundamental for understanding the basis of psychiatric diseases, Tian said.

“I’m very excited about how both drug discovery and basic science can be pushed forward by this technology,” she said.

Tian and former graduate student Grace Mizuno have also founded a company, Seven Biosciences, which has an exclusive license from UC Davis on psychLight and related technology. Their goal is to speed up drug discovery by creating a platform that pharmaceutical companies can use to rapidly screen compounds for neurological effects.

Cannabis coming up green

While Olson is working on analogs of psychedelic drugs, fellow chemistry professor Mark Mascal is working on analogs of cannabidiol, or CBD, one of the active components in cannabis.

Cannabis, like the psychedelic drugs, is a Schedule 1 controlled substance under federal law, although its production, possession and use is legal under state law in California and a few other states. CBD derived from the closely related hemp plant is legal under federal law if certain conditions are met.

One formulation of CBD, sold as epidiolex, is approved by the FDA as a prescription treatment for severe seizures. CBD also has potential for treating metabolic syndrome, cognitive decline and in muscle recovery from injury, Mascal said.

Some people buy over-the-counter CBD from dispensaries to manage conditions such as anxiety. But the potency of retail CBD products isn’t high enough to have therapeutic effects, Mascal said. “It’s probably a placebo effect,” he added.

Legality is still an important aspect of developing CBD as a drug, including internationally, Mascal said. It is relatively simple to convert CBD to tetrahydrocannabinol, or THC, which gives cannabis its psychoactive properties. That raises concern that legalized CBD products could be diverted to produce recreational THC.

Instead, Mascal’s lab works with 8,9-dihydrocannabidiol or H2CBD, a synthetic analog of the drug, which cannot be converted to THC. They developed a method to synthesize H2CBD and showed that it could successfully treat seizures in rats. That work was published in 2019 in Scientific Reports.

Mascal has founded a startup company, Syncanica, to develop similar compounds that he calls pseudo-cannabinoids. These are not, he said, “synthetic cannabis” but entirely different compounds. Mascal hopes to win investigational new drug status for H2CBD from the FDA this year so that the drug can enter clinical trials.

A new center for research

In 2019, UC Davis established the Cannabis and Hemp Research Center as a special program under the Office of Research. Co-directors of the center are Carter and Li Tian, professor of plant sciences in the College of Agricultural and Environmental Sciences. The center facilitates collaborations and supports research related to cannabis and hemp. Research topics range from cultivation and production, the economics of the industry, to experimental research on cannabis derivatives and clinical trials.

Among other projects at the center:

  • Postdoctoral researcher Karen Wagner and Professor Bruce Hammock, from the Department of Entomology and Nematology, are investigating CBD’s potential as a pain medication.
  • Mascal and Michael Rogawski, distinguished professor of neurology, are working on Mascal’s H2CBD as a retreatment for various forms of epilepsy.
  • Professor Keith Baar, Department of Membrane Biology and Physiology, and researcher Henning Langer are leading a study of the effects of CBD and H2CBD in treating congenital muscular dystrophy.
  • Professor Melissa Bauman, Department of Psychiatry and Behavioral Sciences, is studying the effects of prenatal exposure to THC on brain development.

Tyler Lesh, a clinical psychologist in Carter’s lab, is conducting a study of the relationship between cannabis use and psychosis. The work is funded by the California Bureau of Cannabis Control.

Heavy cannabis use is known to be associated with increased risk of psychosis, Lesh said. The risk is highest in childhood and adolescence and is increased in people with a family history of psychosis. But the effects can be positive, including lower blood pressure, better metabolic profile and reduced abdominal girth.

“We’re trying to get a more nuanced picture of how cannabis use impacts people with psychosis,” Lesh said. The study, which began in December 2021, includes volunteers from the community with any degree of psychosis. Subjects get a thorough workup including metabolic profiles, body mass index, questions on activity levels, diet and symptoms, and brain scans.

Using psychedelics to understand the brain

Much of the current research on psychedelic drugs is empirical — taking existing drugs (LSD, MDMA, ibogaine) and testing them against conditions like depression, anxiety and PTSD in patients.

“There’s growing evidence that these drugs work well and work quickly in patients resistant to other treatments,” Carter said.

Yet we still have a very limited understanding of how the brain works and of the causes of these illnesses. Addressing this gap in basic knowledge is the goal of the proposed UC Davis Center for Psychedelics and Neurotherapeutics. To be led by Olson and John Gray, associate professor in the Department of Neurology, and Center for Neuroscience, the center would draw on UC Davis’ unique combination of programs and strengths, including the schools of Medicine and Veterinary Medicine, College of Letters and Science, College of Biological Sciences, California National Primate Research Center and Mouse Biology Program, Neuroscience Consortium, Center for Mind and Brain, Imaging Center and many others.

Modern neuroscience is highly collaborative, Olson said, but working with drugs classed as Schedule 1 by the Drug Enforcement Agency requires a special license. That makes collaboration between universities even harder if the other institution doesn’t have a Schedule 1 license. But the breadth of expertise and facilities available within UC Davis means collaboration within the campus is quite feasible.

“UC Davis is unique because we can do most everything in-house,” Olson said. The center would bring together researchers interested in neurotherapeutics, offering pilot grants for basic research.

The research at UC Davis has the potential to help many patients, Carter said.

“It’s opening a whole new range of approaches, which should offer hope to people with treatment-refractory mental health problems and their loved ones,” he said.

 

Source:magazine.ucdavis.edu, Andy Fell

No Link Between Antidepressants in Pregnancy, Epilepsy in Children

No Link Between Antidepressants in Pregnancy, Epilepsy in Children

There’s good news for women with a mental health condition: Taking antidepressants early in pregnancy doesn’t increase a baby’s risk of having epilepsy or seizures, researchers say.

“The findings of this study are very important,” said study co-author Ayesha Sujan of Indiana University Bloomington. “Pregnancy can be a trying time, and the addition of depression, anxiety and other mental health conditions can add to this burden. These findings may provide reassurance to women and their doctors considering the risks and benefits to medication.”

For the study, the researchers analyzed data on more than 1.7 million children born in Sweden over 17 years. The investigators identified more than 24,000 children whose mothers took antidepressants during the first trimester of pregnancy.

Antidepressants included medications prescribed to treat anxiety and depression, including selective serotonin reuptake inhibitors (SSRIs) like citalopram (Celexa) and escitalopram (Lexapro), as well as serotonin and norepinephrine reuptake inhibitors (SNRIs). The SNRIs include drugs such as desvenlafaxine (Pristiq) and duloxetine (Cymbalta).

Among more than 1.5 million children followed for one month after birth, 0.12% had neonatal seizures. Among more than 1.3 million children followed for two to 17 years, 0.40% were diagnosed with epilepsy.

Initially, the researchers found that rates of neonatal seizures were slightly higher among babies exposed to antidepressants in the womb: 1.7 per 1,000 infants whose mothers took antidepressants during the first trimester and 1.2 per 1,000 among infants whose mothers didn’t take antidepressants.

Rates of epilepsy diagnosis by age 5 were 5.4 per 1,000 among exposed children and 4.1 per 1,000 among unexposed children, according to the study. The results were published online May 11 in the journal Neurology.

But after adjusting for factors in mothers associated with the risk of seizures in newborns — such as age, epilepsy, income and tobacco use — the researchers found no association between antidepressant use by mothers during the first trimester and a child’s risk of seizures or epilepsy.

“While several studies have shown a possible link between antidepressant use by mothers during pregnancy and seizures in newborns and toddlers, our study suggested that antidepressant exposure in the first trimester of pregnancy does not increase the risk of seizures and epilepsy in children,” Sujan said in a journal news release.

“This could mean that the slightly elevated risk for such seizures documented in previous studies could be due to other factors such as other diseases or tobacco use during pregnancy,” Sujan explained.

 

Source: usnews.com, Neurology,  Robert Preidt

Genetic testing results in lower length of stay in the NICU for infants with epilepsy

Genetic testing results in lower length of stay in the NICU for infants with epilepsy

Genetic testing results in lower length of stay in the neonatal intensive care unit (NICU) for infants with epilepsy, according to a study published in the journal Pediatric Neurology.

The reduction in hospital stay time in babies with epilepsy who spent time in the NICU was not explained by changes in the severity of illness, birth weight or population changes in the NICU over time. These findings confirm the importance of early genetic testing for epilepsy, which allows more precise treatment and better seizure control during a critical time in brain development.

Genetic testing allows us to identify the exact gene that causes an infant’s epilepsy so that we can start the most effective treatment as early as possible. The decreased length of stay in the NICU for these infants is an indicator of improved outcomes with precision medicine.”

Andrea Pardo, MD, Study Senior Author and Medical Director of Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program, Ann & Robert H. Lurie Children’s Hospital of Chicago

Pardo is also an associate professor of Pediatrics at Northwestern University Feinberg School of Medicine

Approximately 15% of babies with seizures in the NICU have epilepsy, much of which is caused by single gene diseases. Most NICUs now use epilepsy gene panels, which test for nearly 190 genes known to cause epilepsy. The most common forms of neonatal epilepsy are called ion channelopathies, caused by abnormalities in SCN2A and KCNQ2 genes. Matching treatment to the causal gene is known as precision medicine.

In the study, Dr. Pardo and colleagues evaluated changes in genetic testing for neonatal onset epilepsy and associated short-term outcomes over an 8-year period among a cohort of NICU patients at Lurie Children’s before and after the introduction of sponsored genetic epilepsy testing in January 2018. They included 53 infants who received genetic testing, 20 of which were tested after 2018. As reference, 4,160 infants in the NICU without genetic testing were included.

Researchers found that in the genetic testing group, the length of stay decreased from 25 days pre-2018 to 19 days post-2018. Turnaround time to molecular diagnosis dropped from 51 days to 17 days after 2018. However, this was not the reason for the decreased length of stay for babies with epilepsy.

“Precision medicine resulted in improved seizure control, which is the main reason infants with epilepsy could go home sooner,” said Dr. Pardo. “Our results show higher value with genetic testing for infants and their families, as well as the healthcare system. However, our findings still need to be validated in large, multicenter studies.”

 

Source: news-medical.net, Emily Henderson, Ann & Robert H. Lurie

Sudden Unexpected Death in Epilepsy: 5 things to know according to CDC

Sudden Unexpected Death in Epilepsy: 5 things to know according to CDC

5 Things You Should Know about SUDEP

1. SUDEP is not well understood.

SUDEP stands for “Sudden Unexpected Death in Epilepsy”. It refers to deaths in people with epilepsy that are not from injury, drowning, or other known causes. Most, but not all, cases of SUDEP happen during or right after a seizure.

Researchers do not understand the exact cause of SUDEP, but these are possible reasons it happens:

  • Breathing changes: A seizure may cause a person to have pauses in breathing. If these pauses last too long, they can reduce the oxygen in the blood to a dangerous level. Also, if a person’s airway gets blocked during a seizure, that can lead to suffocation.
  • Heart rhythm changes: Rarely, a seizure may cause a dangerous heart rhythm or cardiac arrest.
  • Other causes and mixed causes: SUDEP may happen because of a combination of breathing trouble and abnormal heart rhythm.

People with epilepsy are at increased risk of SUDEP if they have:

  • Uncontrolled or frequent seizures.
  • Generalized convulsive (what used to be called tonic-clonic or grand mal) seizures.

Other things that may increase a person’s risk of SUDEP include:

  • Seizures that start at a young age.
  • Many years of living with epilepsy.
  • Missing doses of medicine.
  • Drinking alcohol.

2. SUDEP is rare, but traumatic for families.

If you have epilepsy, it’s important to take your seizure medicine as prescribed. The chance of SUDEP is higher in people who have frequent seizures.

Researchers estimate that, for every 1,000 people with epilepsy, at least 1 person may die from SUDEP each year. This means that each year in the United States, there are about 3,000 deaths due to SUDEP. But counting SUDEP cases is hard because SUDEP is not always included on death certificates.

SUDEP occurs more often in people 21 to 40 compared to other age groups. Because SUDEP can happen unexpectedly to people who are so young, it can be very shocking for families and loved ones.

3. Managing seizures may help.

Research has shown that controlling seizures may lower the chance of SUDEP. If you have epilepsy, the most important way to do this is to take your seizure medicine as prescribed.

Other steps that might help lower the chance of SUDEP:

  • Consider a seizure alert monitor if you often have seizures at night.
  • Avoid seizure triggers if you know what they are. Read more about triggers from the EpilepsyU.
  • Don’t drink too much alcohol.
  • Learn how to better control seizures and other symptoms with self-management programs.
  • Get enough sleep.
  • Make sure your family and friends know seizure first aid.

If you are taking medicine and still having seizures, talk to your doctor about changing your medicine or trying other things that might help. If seizures continue, consider seeing an epilepsy specialist.

4. Support is available.

Losing a loved one to SUDEP can be especially hard because it’s so unexpected. The Epilepsy Foundation’s SUDEP provides information and support to families who are grieving.

Parents of children with epilepsy can learn more about SUDEP in children, including tips on how to talk to your child’s doctor.

5. Research continues.

CDC supports research to help us understand SUDEP better. Together with the National Institutes of Health, CDC funds the Sudden Death in the Young Case Registry. The goals of this project are to count the number of cases and to understand the causes of death in infants, children, and young adults who die suddenly and unexpectedly—including from SUDEP. Researchers will use this information to recommend ways to prevent these types of death in the future.

 

Source: tdpelmedia.com, Ngozi Aima

Motorist suffers seizure, crashes into 9 vehicles at traffic lights

Motorist suffers seizure, crashes into 9 vehicles at traffic lights

MELAKA: Six people were injured in an accident involving 10 vehicles when one of the drivers, who is an epileptic, had a seizure at the traffic light intersection at Jalan Tun Abdul Razak, Lebuh Ayer Keroh, here yesterday.

Melaka traffic enforcement investigation department head Amran@Mohamad Zaki Omar said the incident occurred at about 9.15pm when all the victims, involving drivers and passengers in the affected vehicles, were at the Taman Chiptaco traffic light intersection.

 

 

Source: freemalaysiatoday.com, Bernama

Shaken Baby Syndrome: The Very Serious Damage Of Violence On The Newborn Child

Shaken Baby Syndrome: The Very Serious Damage Of Violence On The Newborn Child

Shaken baby syndrome (also called by the acronym SBS, or abusive head trauma or shaken baby syndrome) is a very serious form of physical abuse, mainly – but not exclusively – intra-familial abuse of children generally under one year of age (infants and young children)

Causes of Shaken Baby Syndrome SBS

The causes of SBS are the rapid and violent shaking of the child, which generally occurs over a period of 10-20 seconds.

The baby is shaken violently by the caregiver, usually the father, mother, grandparent or guardian, as an exaggerated reaction to the baby’s inconsolable crying.

The peak incidence of SBS occurs between 2 weeks and 6 months of age, the period of maximum intensity of infant crying.

At that age a shaking movement is particularly dangerous, because

  • the baby does not have full control of its head;
  • the baby’s neck muscles are weak;
  • the baby’s head is heavy in relation to the body;
  • the baby’s brain is of a gelatinous consistency and moves strongly in the skull when the head is shaken;
  • the bone structure is still fragile.

Parents in the first months of a baby’s life, and particularly in the case of a first-born child, are subjected to great stress and sleepless nights that can lead to such exasperation that – at the umpteenth cry – they cause totally irrational reactions, such as shaking the baby violently.

A risk factor that can trigger violent and irrational behaviour towards a newborn child is post-partum depression.

Consequences for the baby of SBS

The consequences of shaking can unfortunately be particularly inauspicious, especially at the nerve level, and are similar (and often worse) to those that can occur in a rear-end car accident: subdural or subarachnoid intracranial haemorrhages, brain contusions and direct nerve fibre lesions are fairly typical events and can lead to brain death of the baby.

Shaking causes a mechanical damaging action related to the abrupt accelerations and decelerations to which the encephalon, cerebral vessels and more generally all tissues are subjected, which – in simple terms – literally slam against the skull back and forth.

The forces generated by the shaking can cause the brain’s white matter axons to stretch and sometimes completely rupture.

The shaking can easily lead to permanent neurological damage with even very severe motor and/or sensory deficits such as paralysis, slowed psycho-motor acquisition, cognitive-behavioural deficits, deafness, retinal haemorrhages, often resulting in central blindness, multiple fractures, mostly of the skull (if there is also impact on the surface), long bones and posterior portion of the ribs.

This can lead to coma or death of the child in one out of four cases.

Shaken baby syndrome: “So much damage from one shake?”

Certainly yes: even a fairly weak and short-lasting shake, which is harmless in an adult, can have disastrous effects on the baby, and it is not by chance that one of the most important precautions in the first months of life is precisely to prevent the baby’s head from being supported.

Some peculiar anatomical features of newborns and infants favour the occurrence of the biomechanical damage already described: fundamental is the considerable volume and weight of the head in relation to the rest of the body mass, the hypotonia of the cervical paraspinal musculature (which causes the typical ‘dangling’ of the head in the first months of life), the high water content of the immature central nervous system, the incomplete myelination of the nerve fibres and the high volume of the subarachnoid spaces compared to the still modest brain volume.

Diagnosis of SBS

Tracing certain lesions to the syndrome may not be entirely easy: they can often be confused with lesions caused by trauma during play.

A thorough investigation by the paediatrician, forensic scientist and law enforcement is always necessary.

Retinal haemorrhages can also potentially be diagnosed with MRI.

Variants of Shaken Baby Syndrome

The Anglo-Saxon term ‘Shaken impact syndrome’ denotes a variant of ‘shaken baby syndrome’, in which the child is not simply shaken furiously, but is thrown violently against a fixed surface, not necessarily hard and rigid, such as a bed.

 

Source: emergency-live.com,

Bridging the gap between adolescent and adult care

Bridging the gap between adolescent and adult care

University of Cincinnati clinics aid patients with disabilities, epilepsy

Medical researchers estimate that about 4.5 million Americans with chronic health conditions are currently moving from adolescence into adulthood.

The process of becoming an adult can be stressful enough, but this population has the added challenge of no longer being able to get care from the pediatric health care team they are familiar with and having to find new adult health care providers.

Researchers at the University of Cincinnati have studied best practices to make the transition from pediatric to adult care a more streamlined process and have launched two transition clinics to help patients in this process. Jensine’ J. Clark, MD, leads the Physical Medicine & Rehabilitation (PM&R) Transition Clinic at the UC Gardner Neuroscience Institute (UCGNI) for patients with childhood-onset disabilities, while Emily Nurre, MD, leads the Epilepsy Transition Clinic.

PM&R Transition Clinic

Pediatric-onset disability is a broad term used to describe any disability that happens to a child and affects their development, Clark said, including spinal cord injuries, spina bifida, cerebral palsy or any condition that causes developmental delay.

“Previously, children with pediatric-onset disability didn’t live into adulthood, and so our general understanding of the processes and what adults with childhood-onset disabilities look like is relatively new in terms of the field of medicine,” said Clark, assistant professor in the Department of Neurology and Rehabilitation Medicine in UC’s College of Medicine and a UC Health physician. “Unfortunately, we did not have enough robust systems to care for them once they became adults, and that care continuum was not always smooth.”

Many patients can feel anxiety in having to begin a relationship with new doctors, therapists and others after engaging with the same care team for years, Clark said. The clinic has three main objectives as patients make the transition to adult care.

First, the team works to develop a transition action plan and an individualized treatment plan for each patient, which includes identifying what providers the patient is currently seeing and who they need to continue to see in adult settings.

“As the rehab doctor, we are serving as the quarterback of all the different other specialties,” Clark said. “For example, patients were seeing a pulmonologist, but they may not need to continue that into adulthood. So the first thing is to identify what type of providers they need to transition.”

The PM&R Transition Clinic helps facilitate services including primary care, neurology, neurosurgery, musculoskeletal interventions, orthopedics and OB/GYN. The clinic also offers a unique gait lab that can observe how patients walk and help them walk more easily.

It makes you feel very safe, and the professionals just work very well together. They bring out the best in each other. You can just see that it’s an organized, cohesive team that’s there to support each other as well as the patient and anyone that comes along with the patient.

 Geri McCarthy, mother of PM&R Transition Clinic patient MacKenzie McCarthy

In addition to coordinating and providing care, the second objective of the clinic is to focus on the social aspects that come with transitioning to adult care.

“It’s helping to navigate if there are insurance changes, the school to either work or community integration changes and making sure they have those peer support groups,” Clark said.

Finally, Clark said the clinic helps encourage parents to take a more passive role in their children’s care and empower the patients themselves to manage their own health care.

“For the child’s whole life, the parent has been No. 1 in the room. You address the parent, you talk to the parent, but now we’re transitioning those skills from the parent to the child,” she said.

“It affects everybody differently, because the parents feel like they’re getting kicked out, and so there’s that feeling of separation.”

Clark completed a PM&R residency at UC and returned after a fellowship specifically to build the PM&R Transition Clinic as a partnership between Cincinnati Children’s Hospital Medical Center (CCHMC) and UC/UC Health. Her previous experience has been helpful in building trust and relationships between the entities, she said.

“Having trained here, and working with people on both the pediatric and adult side, people are familiar with me as a person,” Clark said. “So that gives credence when they’re counseling their families and saying, ‘I know Dr. Clark personally and I know that she’s going to help take great care of you.’ That lends a lot of confidence to the patients and families.”

Epilepsy Transition Clinic

Nurre said patients with epilepsy have many of the same struggles when learning how to take responsibility for their own care, which can include sticking with their medication regimen, knowing safety practices to help prevent seizures and filling their own prescriptions.

“Epilepsy patients in general have a high rate of comorbidities like depression and anxiety, among other things, and so that’s also a challenge for this patient population especially in these years,” said Nurre, assistant professor of neurology and rehabilitation medicine at the UC College of Medicine and a UC Health neurologist. “A lot of what I do is making multidisciplinary, community, and provider partnerships to bring people together to help this population, because it takes a village.”

Nurre and her UC colleagues collaborate with CCHMC and Epilepsy Alliance of Ohio staff to hold the transition clinic once a month in West Chester, Clifton or Florence locations.

Through research including discussion with transition health care providers and patient focus groups, the team determined patients should be introduced to the need to transition to adult care around age 13 and no later than age 16. Patients meet with Epilepsy Alliance social workers at their final pediatric visit and their first visit on the adult side.

“We found that patients really wanted a warm handoff, somebody that they knew and trusted through the process of transitioning,” Nurre said. “We are grateful that the Epilepsy Alliance social workers provide an additional trusted source of information and assistance during transfer from pediatric to adult care.”

As patients begin to see adult providers, Nurre said the transition continues with education initiatives and ongoing work to set the patients up for success.

“There’s often a high rate of no-shows, medication and care gaps, and lack of skills to navigate the adult health care system. It’s a time where it’s easy for patients to get lost in the gap between pediatric and adult care,” she said. “We are working to create a more streamlined, standardized process for the patients that makes it easier for them to transfer and decrease chances of missed medications, seizures, emergency department visits and gaps in medical care.”

Clara’s story

Clara Hartman transitioned her epilepsy care from CCHMC to UC Health when she was 21. She said the transition team helped make it a positive experience.

“They know where you’re coming from, so it’s not like they expect you to be a fully fledged adult. They know you’re coming from Children’s, and it’s really important to have somebody who understands that,” she said. “If they didn’t have such a good transition in place, I may not have kept up with my epilepsy care like I should have. I know myself, and I probably wouldn’t have followed through with setting up my own appointments and it would have been horrible.”

Hartman said even as she has taken a more active role in her care, she is still grateful for reminders and encouragement from her mom along the way.

“She’s always super supportive in making sure I make the appointments that I need to make and make the calls I need to make,” Hartman said. “It turned more into my mom asking me about it so that I can tell her rather than her just telling me about it. So she’s still active and involved in a what are you doing kind of way.”

While Hartman has transitioned to adult care, CCHMC is continuing to have an impact on her life. Her positive experience with the psychologist she saw as a patient inspired her to pursue a career in clinical psychology, and she currently works at CCHMC as a clinical research Long term, Hartman hopes to earn her PhD in clinical psychology and return to Children’s working in integrated behavioral health.

MacKenzie’s story

MacKenzie McCarthy became a PM&R Transition Clinic patient several months ago. MacKenzie has cerebral palsy and quadriplegia and had been treated by a team at CCHMC her whole life.

MacKenzie’s mother Geri said they were both a bit apprehensive to transition to a new care team, but they were encouraged by Clark’s approach to beginning the process when they first spoke together.

“They kind of gave us the clue that she was interviewing MacKenzie as much as MacKenzie was interviewing her, that Dr. Clark didn’t want to take on people where it wasn’t going to be a good fit,” Geri said. “The gist was they wanted it to be a positive experience for both parties.”

MacKenzie, an avid Cincinnati sports fan, recalled she was decked out in Bengals gear at her first appointment in Clark’s office and felt immediately welcomed when the office staff broke out into a Bengals cheer.

“It makes you feel very safe, and the professionals just work very well together,” Geri said. “They complement each other. They bring out the best in each other. You can just see that it’s an organized, cohesive team that’s there to support each other as well as the patient and anyone that comes along with the patient.”

In addition to rehab with Clark, the PM&R Clinic is coordinating dental, primary care, physical therapy and neurosurgery services for MacKenzie. MacKenzie has learned to become an advocate for herself over the years, and Geri said she was grateful to see Clark and her colleagues respectfully talk with MacKenzie without talking down to her.

“I’m just her sidekick it seems, and I’m fine with that because I don’t want to be that helicopter parent,” Geri said. “MacKenzie knows her body and they know that. It’s been real responsible, respectful exchanges, which is wonderful. They appreciate what she brings to the party.”

The McCarthys said it is particularly appreciated that the adult care team and facilities are welcoming and safe, from the heated garage with adequate spacing for their custom-made lift van and prominent directory signs at UCGNI to large rehab rooms that are wheelchair accessible.

“It ended up being an answer to a prayer, and all the people that we’ve met so far have been fantastic,” Geri said. “When you have a person that is disabled and can easily get sick, and you go to a facility that’s clean and spacious and you feel like they’re taking all precautions to ensure the patient and family’s safety, it means the world to us.”

For more information about the PM&R Transition Clinic, call 513-418-2225. For more information on the Epilepsy Transition Clinic, email emily.nurre@uc.edu.

 

Source: uc.edu, Tim Tedeschi

Trees Forever plants ‘beautiful legacy’ to raise epilepsy awareness in honor of late Joe Drahos

Trees Forever plants ‘beautiful legacy’ to raise epilepsy awareness in honor of late Joe Drahos

30 trees are planted along Cedar Rapids’ Grande Avenue SE

CEDAR RAPIDS — When Pat Drahos’ late son, Joe, was about 10 years old, he had endless adventures with his best friends playing along the Grande Avenue SE boulevard.

She remembered him posing for photos when the boulevard was put there in the 1990s. In the winter, Joe and his neighbor friends B.J. and Carl would mound piles of hard snow into a fort — “which really isn’t safe when you consider that’s where the cars would slide into,” Drahos said with a smile.

But B.J. assured her at the time that they were sensible builders: “We had to cut a window out of it so we could stick our head out and see if a car was coming.”

Joe died last August at age 33 of Sudden Unexpected Death in Epilepsy (SUDEP). He had his first grand mal seizure at 22, and was diagnosed with epilepsy six months later after a second seizure.

His epilepsy worsened with time, disrupting his ability to work as a petroleum engineer and go about his usual activities. Joe loved football, was a skillful piano player and was devoted to his family.

After the 2020 derecho, Joe returned from California and was stunned to see the fallen trees — toppled by the storm’s hurricane-force wind gusts — lining his childhood play place.

“When he passed, it just seemed only fitting I thought we would get maybe one or two trees,” Drahos said.

But with the help of Marion-based nonprofit Trees Forever, there will be over 30 trees planted along Grande Avenue SE, from the Drahos’ house on the 1900 block toward Third Avenue SE, in Joe’s honor and to raise epilepsy awareness.

The Drahos family approached Trees Forever and had secured over $6,500 in funding from the community and some donors around the country to support the tree planting and maintenance.

As Trees Forever’s community project, the organization will provide two years of care for the new trees. The nonprofit purchased the trees at-cost, about $250 to $300 per tree.

About 20 Trees Forever staff and some volunteers helped plant the trees Wednesday afternoon. Honey locust, Kentucky coffee and tulip trees, said to be Joe’s favorites, were planted in front of the Drahos’ house and will provide a gold flower canopy in the fall. Swamp white oak, American sycamore and London plane trees also were part of the planting.

Kiley Miller, Trees Forever president and chief executive officer, said this project was planned before the organization’s ReLeaf partnership with the city of Cedar Rapids to help replenish the tree canopy lost in the derecho.

“This family and the people on this street will remember Joe every day when they see these trees grow, and that is a beautiful legacy,” Miller said.

The Drahos family planted four trees last fall — two outside their house — and lined them with purple battery-operated string lights, a nod to the color for epilepsy awareness.

“People look at them now and think of Joe,” Drahos said.

She hopes the trees help raise awareness of epilepsy and educate people that those with epilepsy are not unemployable and need accommodations.

According to the U.S. Centers for Disease Control and Prevention, there are about 3.4 million people with epilepsy nationwide — 3 million adults and 470,000 children. There are 31,400 in Iowa.

Epilepsy can be caused by different conditions that affect a person’s brain. The cause is often unknown, but some causes include stroke, brain tumor, central nervous system infection and traumatic brain injury or head injury.

Around two-thirds of people with epilepsy can control their seizures with medication, but the rest do not gain seizure control.

“I want (people) to know that this is not uncommon, and that there is no cure, that we need a lot more research,” Drahos said.

 

Source: thegazette.com, Marissa Payne

New Mobile App Giving People With Epilepsy Advanced Warning Of A Seizure

New Mobile App Giving People With Epilepsy Advanced Warning Of A Seizure

A new mobile app feature – made here in Australia – is bringing new hope to epilepsy sufferers worldwide.

The innovative technology, which has been 10 years in the making, is designed to help better diagnose and forecast epileptic seizures in real time.

The free app known as Seer Epilepsy Management, developed by Melbourne-based med tech Seer Medical as a non-invasive management tool, will now include the soon-to-be released forecasting tool.

It also has a bunch of other tools for sufferers including medication reminders, and the ability to log seizure events and previous medical history.

Patients can record their symptoms as well as previous episodes on the app, which then collates patterns and possible triggers and predicts seizures up to a month in advance.

The app will collate patterns to help predict seizures. Credit: Seer Medical

The technology is set to be a game-changer for the thousands of sufferers who experience unpredictable seizures.

The Epilepsy Foundation of Australia said for the 250,000 people across the country currently living with epilepsy, the “worst part” of having seizures is that they happen with little or no warning.

“The uncertainty of seizures puts people in danger – even ‘small’ seizures can result in serious injuries or death if they happen while driving, in the shower, cooking or pouring a kettle, climbing stairs or other everyday activities,” it said.

“Unfortunately, this means people with epilepsy sometimes have to give up their driver licence, modify or quit certain hobbies, and they or their family may experience anxiety in their day-to-day lives.”

The Foundation added that two-thirds of people who suffer from the debilitating condition can eliminate their seizures by taking medications.

But this leaves about 24 million people, worldwide, living with unpredictable seizures.

“If people had some warning of when their seizures were more likely, it could reduce their stress and improve safety,” the Foundation said.

Hamish Macmillan, who suffers from epilepsy, told he experiences on average 10 seizures each year and has to be extremely careful when undertaking various tasks.

“That’s anything from taking a shower by yourself, to crossing the road, anything that might be slightly or mildly dangerous I have to think twice about,” he said.

“I’ve learnt to manage it, and it has gotten better, but the worst part is still just that unpredictability element of it.”

The app can also be linked to a smartwatch that can track body movements and vital signs.

 

Source: vervetimes.com,

Japan Considers Very Limited Medical Cannabis Reform

Japan Considers Very Limited Medical Cannabis Reform

Japan’s Health Ministry is considering reforming the nation’s cannabis laws to provide for the legal use of medical cannabis.

A panel comprised of Japan Health Ministry experts met last week to continue discussions regarding revisions to Japan’s 1948 Cannabis Control Law.

It’s the latest step in what will likely be a very lengthy process to explore legalizing medical cannabis in Japan.

What is being proposed in Japan, if enacted, would only legalize medical cannabis in very limited forms and situations.

Only cannabidiol (CBD) would be legalized, whereas tetrahydrocannabinol (THC) would remain prohibited. Even the limited CBD reforms that are being proposed in Japan are being met with some skepticism among health experts in the country for whatever reason.

June 2021 Report

The discussions currently underway in Japan are the result of a report that was released nearly a year ago in June 2021.

The report, which was compiled by Japan’s Health Ministry, recommended that CBD be allowed to treat refractory epilepsy.

CBD has been found to effectively treat refractory epilepsy, and it is commonly prescribed to help treat the condition in a growing list of countries.

Japan’s current cannabis laws are largely built on the concept of banning parts of the cannabis plant, versus focusing on cannabinoids and limits of cannabinoid content.

Banning parts of the cannabis plant seems to be a common concept in the region when it comes to cannabis policy whereas in Western countries hemp, which is what CBD is largely sourced from, has a THC percentage limit for both harvests and finished products.

Unfortunately, the ministry panel is also recommending that a new law be created that would harshly punish people for simply using cannabis for non-medical purposes, which is a particularly harsh policy.

It’s unclear how such a cannabis policy would be enforced, however, it’s a safe assumption that people suspected of having cannabis in their system would likely be automatically tested, which would be a massive invasion of privacy and is a policy that is ripe for selective enforcement .

Why Is Japan So Scared Of Cannabis?

People all over the planet, including in Japan, have used the cannabis plant for medical and / or recreational purposes for centuries. By historical standards, the cannabis plant was only banned recently, and even then, the enactment of prohibition was based on harmful political ideology and not on sound science.

Cannabis prohibition is one of the most harmful public policies on earth, and that is particularly true in Japan where cannabis prohibition is being used to ruin many lives.

Over the course of the last 8 years, the number of people being arrested for cannabis in Japan has increased, even though cannabis arrests have decreased in many other countries during the same time period.

The rise in cannabis arrests culminated in a record being set in 2021, with a reported 5,482 people being arrested for cannabis offenses in Japan during the last full calendar year.

Roughly 70 percent of the arrests involved suspects that were teenagers or in their 20s.

The rise in arrests is an indication of heightened cannabis prohibition enforcement by Japan in recent years, although Japan’s government is portraying the rise of arrests as being the result of increased consumption rates.

In reality, Japan has one of the lowest cannabis consumption rates on the planet. Consider the fact that only 1.8% of people in Japan report having consumed cannabis during their entire life.

Japan doesn’t have a cannabis use problem. It has a cannabis prohibition problem, and that problem will only get worse if Japan enacts a new anti-cannabis consumption law.

 

Source: thehealthguild.com

Kids with additional needs lose ‘lifeline’ summer school

Kids with additional needs lose ‘lifeline’ summer school

Angry families have slammed cuts to a “lifeline” summer service at a school for kids with additional needs.

They hit out after East Renfrewshire Council cancelled two weeks of holiday activities at Isobel Mair School, in Newton Mearns, for more than 100 primary and secondary pupils.

The cost-cutting move means the sessions will now only be provided for 37 children, over fewer days.

Barrhead woman Selina Yau, 30, who is a carer for her 16-year-old brother, claims families have been left in the lurch and will have to take extra time off work.

The social worker said the annual two-week programme gave stressed-out parents and carers a much-needed break over the summer.

She launched a petition on May 20 calling on council chiefs to reverse their decision and, within days, it had attracted thousands of signatures.

Selina, whose brother has autism and epilepsy, said: “This will significantly impact on the mental health and wellbeing of the pupils.

“This time is also invaluable to parents and carers who are able to get a small break during the long summer holiday.

“Many viewed the two weeks as a lifeline, as they are also able to use this time to focus on their other children.”

Although the move will save cash-strapped council chiefs tens of thousands of pounds, Selina believes it could prove costly in the long term, as many parents and carers will have to seek support from the local authority if they are unable to get time off work to look after their children.

She added: “We are appalled that the council made this decision at such short notice, without consulting the children or us.

“There are not many out there who are qualified to look after young people with complex needs.

“The decision has effectively extended the school holidays from five to seven weeks, leaving most parents unable to find or afford alternatives.”

Chloe Muir’s eight-year-old son Callum has Down’s Syndrome and autism and has attended Isobel Mair School since he was four.

The 50-year-old police officer and her husband were stunned when they found out there would be no place for Callum this summer.

Chloe told the Barrhead News: “My reaction was one of shock and disbelief.

“We can’t ask people to babysit, like other parents, because of Callum’s special needs.

“The two weeks every summer gives my husband and I much-needed respite.

“We do not have a social life, we do not go out together, except with the children.

“For us, these two weeks are critical.”

Chloe, who lives in Busby, says Callum needs round-the-clock care, has to be fed through a tube and requires oxygen at night.

“I can’t understand why the council think this money-saving idea is a step in the right direction,” she added. “There ‘s been no thought put into it at all.

“I do not think they realise what the knock-on effect will be. It’s a huge setback for the children and their care.

“You’re talking about the most vulnerable people in society being badly let down.”

Barrhead dad Paul Dickson’s 10-year-old twins Eva and Luke, who are both severely autistic, are among the 37 pupils who have been offered summer school places – but the number of days has been reduced from 10 to six.

Paul, 46, said: “There has been no negotiation or consultation. They are taking support away from some of our most vulnerable kids.

The long-term damage this will cause far outweighs any savings which are being made.

“We don’t blame the school – the decision has come from the council. It doesn’t seem very smart or very fair.”

Members of Isobel Mair School Parent Council were due to meet with officials last night to discuss the cutbacks.

A spokesperson said: “The Parent Council are distressed and hugely concerned about the impact of the cuts to the extended school year on pupils and their families.

“We’ve never had such an overwhelming response, with many deeply worried about what they will do and the impact on their mental health.

“Families have been informed of these cuts with only six weeks notice and no suitable alternative available.

“Emails to the Director of Education, voicing our concerns, as yet remain unanswered.”

Michael McEwan, of the East Renfrewshire Disability Action campaign group, also slammed the summer school cutbacks.

He said: “ There was no consultation carried out. This has had a devastating effect on parents.”

A spokesperson for East Renfrewshire Council said: “We understand that the proposed change to the structure of holiday provision at Isobel Mair will be difficult for those impacted.

“Unfortunately, like all councils, we continue to face extremely challenging financial pressures and, when the budget for 2022/23 was set in March, a range of tough savings had to be made

The additional holiday provision previously available for all in Isobel Mair has been redesigned to support children with the most complex needs, as we try to mitigate the impact of the saving as much as possible.

“We continue to work closely with a range of partners to identify suitable alternative support measures for families.”

 

Source: barrheadnews.com,  Norman Silvester

New treatment option available for Dravet syndrome

New treatment option available for Dravet syndrome

Global biopharma company UCB says the UK’s National Institute for Healthcare Excellence (NICE) has issued a positive Final Appraisal Determination (FAD) for its FINTEPLA (fenfluramine) oral solution.

FINTEPLA is used for the treatment of seizures associated with Dravet syndrome as an add-on therapy to other anti-epileptic medicines for patients two years of age and older.

Dravet syndrome is a rare, lifelong epilepsy that begins in infancy.

It has an estimated incidence rate of one in 15,700 people. Common issues associated with Dravet syndrome include: prolonged and frequent seizures, behavioral and developmental delays, movement and balance problems, orthopedic conditions, delayed language and speech issues, growth and nutrition issues, sleeping difficulties, chronic infections, and sensory integration disorders.

Patients with Dravet syndrome face a 15-20% mortality rate due to SUDEP (sudden unexpected death in epilepsy), prolonged seizures, and seizure-related accidents such as drowning, and infections.

“Given that Dravet syndrome is particularly challenging to treat, we are acutely aware of the ongoing unmet medical need for people living with this condition. This news underscores the wider recognition of addressing this unmet need and echoes UCB’s ongoing commitment to the epilepsy community,” said Claire Brading, managing director, UK & Ireland, UCB. “We are delighted to have received this positive NICE decision and look forward to making this treatment option more widely available as an add-on therapy for Dravet syndrome patients in the UK.”

Galia Wilson, chair and trustee of Dravet Syndrome UK, whose son has the condition, said: “Dravet syndrome is a catastrophic condition which has a devastating impact on every aspect of life. Individuals with the condition and their families are in urgent need of improved treatments and care.”

Wilson said as Dravet syndrome can be unpredictable, like many of the current treatments, fenfluramine may not work for all. However, she added, from clinical and real-life experience, it can be transformative.

New treatment option

Professor Helen Cross, The Prince of Wales’s Chair of Childhood Epilepsy & Head of UCL-ICH Neurosciences Unit, said one of the many complexities of Dravet syndrome is that seizures are usually treatment-resistant.

“Children with Dravet syndrome suffer from frequent and prolonged epileptic seizures, affecting quality of life for both them and their caregivers,” Cross said. “Fenfluramine has demonstrated an impressive reduction in seizures in clinical studies, so this positive decision from NICE means an effective new treatment option and hope for an improvement in quality of life for families concerned.”

Other companies such as Austrian biotech a:head bio AG are also working on combating neurological disorders including Dravet syndrome. Last year, the company secured more funding to recreate human brain disorders in a lab setting.

In late 2022, a:head is planning a series A financing round to prepare for its next growth phase.

 

Source: labiotech.eu, JIM CORNALL

Adults in 50s and Seizure Outcomes Following Resective Epilepsy Surgery

Adults in 50s and Seizure Outcomes Following Resective Epilepsy Surgery

Age 50 years and older should not be considered an exclusion criterion for resective epilepsy surgery (RES) in patients with drug-resistant temporal lobe epilepsy (TLE), according to a retrospective analysis published in the journal Neurochirurgie.

Surgery is an effective treatment for patients with drug-resistant TLE. However, it’s not commonly done in older patients because of a perceived higher probability of perioperative complications, cognitive decline, and worse seizure outcomes. The objective of the current study was to screen all individuals who underwent this surgery at Centre Hospitalier Régional Universitaire de Nancy (CHRUN) in Nancy, France, from January 2007 to March 2019.

The primary study endpoint was freedom from disabling seizures (Engel I) at 2 years postoperatively. Secondary endpoints included occurrence of surgical complications and neuropsychological outcome within 1 year postoperatively. The results were compared with those from a younger patient population who underwent surgery during the same time period.

Among a total of 19 participants aged 50 years and older, the mean age at the time of surgery was 54.94± 5.06 years (range, 50 to 69 years), compared with 34.12±8.36 years (range, 18 to 49 years) among the younger patient population. Further, the male-to-female ratio was significantly higher in the group of patients aged 50 years and older than in those younger than 50 years of age (0.93 vs 0.36, respectively).  The mean duration of epilepsy at the time of surgery was 20.43 years among younger patients compared with 36.6 years among older patients, with the difference between both groups being statistically significant.

At 2 years postoperatively, the rates of Engel I seizure outcome did not differ significantly between individuals younger than 50 years of age and those 50 years of age or older (73.9% vs 94.4, respectively). Postsurgical complications were experienced by 11.9% of younger participants and 47.7% of older participants.

An early neurologic deficit (ie, within 1 week postsurgically) was reported in 7.4% of the younger participants vs 42.1% of the older participants. Within a period of 6 weeks, the neurologic deficit was resolved without sequelae among 6% of those in the younger patient group vs 36.8% of those in the older patient group. Oculomotor deficits — the most common form of neurologic deficit — were reported in 3% of younger individuals and 26.3% of older individuals.

Study limitations included its small sample size of patients aged 50 years and older, along with its single-center, retrospective design. Further, the possibility cannot be excluded that selection bias existed, with only those individuals with the highest likelihood of attaining good postsurgical results being chosen.

The researchers concluded “Patients aged ≥50 years had an excellent seizure outcome at 2 years postoperatively,” with nearly 95% of these individuals achieving freedom from disabling seizures at 2 years postoperatively.

 

Source: neurologyadvisor.com, Sheila Jacobs

Groove rhythm stimulates prefrontal cortex function in groove enjoyers

Groove rhythm stimulates prefrontal cortex function in groove enjoyers

Abstract

Hearing a groove rhythm (GR), which creates the sensation of wanting to move to the music, can also create feelings of pleasure and arousal in people, and it may enhance cognitive performance, as does exercise, by stimulating the prefrontal cortex. Here, we examined the hypothesis that GR enhances executive function (EF) by acting on the left dorsolateral prefrontal cortex (l-DLPFC) while also considering individual differences in psychological responses. Fifty-one participants underwent two conditions: 3 min of listening to GR or a white-noise metronome. Before and after listening, participants performed the Stroop task and were monitored for l-DLPFC activity with functional near-infrared spectroscopy. Our results show that GR enhanced EF and l-DLPFC activity in participants who felt a greater groove sensation and a more feeling clear-headed after listening to GR. Further, these psychological responses predict the impact of GR on l-DLPFC activity and EF, suggesting that GR enhances EF via l-DLPFC activity when the psychological response to GR is enhanced.

Introduction

A growing amount of evidence shows that physical exercise has beneficial effects on cognitive functions, especially on human executive function (EF) mainly in the prefrontal cortex (PFC). Our recent study using acute exercise with music showed that the key factor of exercise’s effect on prefrontal executive function is a positive affective response expressed the two-dimensional axis of pleasure and arousal.

Another potential stimulus which can improve EF through a positive affective response is groove rhythm (GR). GR is a musical rhythm that induces the sensation of “Wanting to move to the music” (groove sensation) accompanied by positive affective responses while listening to music. GR can be defined by the subjective score of “Wanting to move to the music” and “Good nori”. The groove sensation can be modulated by syncopation. Syncopation is a method of shifting rhythmic emphasis by manipulating the complexity of a rhythm. Rhythm with low to medium syncopation induces a higher groove sensation than does rhythm with high syncopation as evidenced by averages of mass groups in previous studies. Low-frequency components, such as the bass drum, induce entrainment of body movement and musical beat. In several previous studies, drum breaks consisting of hi-hat, snare-drum, and bass-drum sounds were used because they made it easy to control rhythmic factors, syncopation, bass sound, and tempo.

Moving the body to music is a universal phenomenon (e.g., clapping, nodding, swaying) and one of the main powers of music. Music with groove-inducing characteristics increasing in recent music popularity charts may be indicative of this. That groove music improves gait performance in Parkinson’s disease (PD) by reducing the cognitive demands of synchronizing to the beat and promoting vigorous movement shows that groove music affects the interaction between body movement and brain function. More interestingly, listening to groove music induces entrainment of body movement and musical rhythm together with positive affective responses and activates neural networks associated with motor and reward systems. Since the dopaminergic reward system projects not only to emotion-related brain areas but also to cognition-related areas such as the PFC, GR could increase prefrontal cortex (PFC) activity and lead to improved EF. However, no research has explored the effect of groove music on executive function (EF) and prefrontal activity to date. The reason for this could be that the effect of GR on EF may have large individual differences because both groove sensation and concurrent positive affective responses to groove music would have many individual differences and both responses are associated with reward system activity. Therefore, we should examine the single effects of GR on EF and its relationship with PFC activity. To examine this, consideration of the psychological responses to listening to groove rhythm (GR) as influential factors that explain individual differences and creation of an experimental model which can evaluate the effect of GR on EF and how it is related to PFC activity are necessary.

To that end, in the current study we introduce the combination of an acute experimental model that was used for the detection of exercise’s effect on cognition and prefrontal activity and a grouping analysis to explore the psychological response to GR. In our previous research, we used functional near-infrared spectroscopy (fNIRS) with the color-word-matching Stroop task (CWST), which evaluates inhibitory EF, in order to clarify the effects of an acute bout (10 min) of exercise. fNIRS is a non-invasive neuroimaging method which can monitor hemodynamic response to neural activation (neurovascular coupling) by using near-infrared light passing through tissue. Since fNIRS allows for the least restrictive measuring environment among neuroimaging modalities, it can measure regional cortical activation boosted by listening to music while minimizing possible negative environmental influences on psychological response and cognition. The CWST has been adopted in numerous neuroimaging studies including fNIRS studies, and the brain regions related with the task are well known. The DLPFC is a key region for inhibitory control of EF and responsible for CWST performance. In addition, the left hemisphere plays a key role in the processing of verbal information. Therefore, we focused on the left dorsolateral prefrontal cortex (l-DLPFC) as the region of interest (ROI). A previous study indicated that l-DLPFC activity correlated with a positive affective response and that EF changed with a single bout of exercise with music. Therefore, in the current study, the color-word-matching Stroop task (CWST) was performed before and after listening to GR while monitoring l-DLPFC activity using fNIRS. In addition to this acute model, cluster analysis using the subjective senses of both groove sensation and psychological state when listening to GR was introduced, and we tried to reveal the individual differences in the effect of listening to groove rhythm (GR) on EF and task-related l-DLPFC activity.

GR elicits groove sensation and concurrent positive affective response, but it is not known whether it enhances inhibitory executive function (EF) with dorsolateral prefrontal cortex (l-DLPFC) activity as a result. The purpose of this study is to determine whether GR enhances EF and l-DLPFC activity, focusing on individual differences in psychological responses to GR. Our working hypothesis is that GR presented as drum breaks with low to medium syncopation enhances CWST performance with task-related l-DLPFC activation. Furthermore, the effects can be remarkable in participants who experience a higher groove sensation and positive psychological state. This study will allow us to look ahead to new aspects of the effect of GR, for example a potential cumulative effect with exercise.

Results

Physical load and psychological measures

Physical load and psychological measures for each experimental condition for all participants are shown. Paired t tests were conducted over condition (WM, GR). We confirmed that there were no differences in HR between conditions. GR elicited significantly higher scores compared to WM in these items: “Good nori”, “Wanting to move to the music”, “Feeling like my body is resonating with the rhythm”, “Having fun”, “Excited”, and “Feeling clear-headed”. WM elicited significantly higher scores compared to GR in these items: “Struggling to synchronize with the beat”, “Bored”, “Wanting to stop listening”, and “Feeling discomfort”.

Discussion

The purpose of this study was to determine whether GR enhances EF and DLPFC activity, focusing on individual differences in psychological responses to GR. To achieve this purpose, the current study tested the hypothesis that GR presented as drum breaks with low to medium syncopation enhances CWST performance with task-related l-DLPFC activation, and that the effects can be remarkable in participants who show higher groove sensation and positive psychological state. To our knowledge, this study presents the first experimental evidence for the enhancing effects of GR on EF and l-DLPFC activity in only participants for whom listening to GR largely augments both groove sensation and feeling clear-headed. In addition, these psychological responses to listening to GR were shown to predict EF and l-DLPFC activity.

First, as a precondition of the experiment, we confirmed that drum breaks with a low to medium degree of syncopation (GR) induced groove sensation (e.g., “Wanting to move to the music”, “Good nori”) and positive affective response (e.g., “Having fun”, “Excited”) compared with the WM by comparing average values. This agreed with previous studies showing that drum breaks with a low to medium degree of syncopation induce higher groove sensation. To make the rhythm more interesting to listeners and to thus induce groove sensation and the related positive affective responses, a balance between expectation and violation of the rhythm is thought to be important. This is supported by the hypothesis that prediction error (deviation from predicted rhythm) is a requisite for music to activate the reward system in the brain. Since the validity of our experimental design was confirmed, we proceeded to the detection of the effect of GR on cognitive function.

Regarding EF and l-DLPFC activity, we confirmed that there was Stroop interference in both Stroop task performance and l-DLPFC activity. However, there were no significant differences between experimental conditions. One possible reason for this is extensive individual differences in psychological response to groove rhythm (GR). Thus, we conducted a sub-group analysis to consider the influences of individual differences in psychological response. Using the k-means clustering method in which “Good nori” and “Feeling clear-headed” were the variables, participants were divided into three clusters. The results show that only in participants who felt a high groove sensation and a high feeling clear-headed (“Groove-familiar” cluster), listening to GR significantly enhanced executive function (EF) and l-DLPFC activity compared to the WM condition. Conversely, GR significantly decreased EF in the participants who felt a relatively low groove sensation and a low feeling clear-headed (“Groove-unfamiliar” cluster). Furthermore, using path analysis, we detected a potential causal relationship between groove sensation, psychological state, dorsolateral prefrontal cortex (l-DLPFC) activity, and EF. The model described that groove sensation influenced both psychological state and l-DLPFC activity and that psychological state influenced EF and l-DLPFC activity. When interpreting neural activity, it should be considered together with task performance. With regard to improved task performance, neural activity may decrease, remain unchanged, or increase. A decrease or no change in neural activity despite an improvement in task performance can be interpreted as an increase in neural efficiency. Gender, task difficulty, and training are known to be influential factors of neural efficiency. On the other hand, if neural activity increases with improved task performance, it can be interpreted as an increase in neural activity to achieve higher task performance. In the present study, increased l-DLPFC neural activity was positively correlated with better color-word-matching Stroop task (CWST) performance, suggesting that the l-DLPFC neural activity led to higher EF. This interpretation has also been validated by other previous studies including our own. These results suggest that groove sensation and psychological state are important predictors, and these factors influence the effect of GR not only positively but also negatively.

The participants who were grouped in the “Groove-familiar” cluster experienced positive effects of GR on EF and l-DLPFC activity. Successful entrainment and body movement to a musical beat (rhythmic entrainment, sensorimotor synchronization) could be among the important factors for promoting the positive effects of GR. Generally, music induces positive affective responses and concurrently increases dopamine release and brain activation related to the reward system including the basal ganglia (BG), midbrain, and orbitofrontal cortex, whereas rhythmic entrainment reinforces both groove sensation and positive affective responses and recruits brain regions related to both the motor and reward systems through BG activity, which plays a key role in the connection of rhythmic entrainment and positive affective responses. That groove music recruits not only the reward system, but also the motor system indicates that the body and musical entrainment are the bases of inducing a positive affective response. In addition to recruiting the dopaminergic reward system, high-groove music also induces physiological arousal related to the noradrenergic system, which is part of the catecholamine system, inducing brain activation. A positive affective response involving the catecholamine system can trigger the enhancement of executive function (EF) and related DLPFC activity. Considering that both groove sensation and positive affective responses were together correlated with BG activity in a previous study and that the current data shows that both groove sensation and feeling clear-headed are influential factors in the effect on dorsolateral prefrontal cortex (l-DLPFC) activity and EF, we could postulate a relationship between rhythmic entrainment, psychological responses, the catecholamine system, and prefrontal function. Thus, “Groove-familiar” participants may have achieved successfully entrainment to GR, enhanced groove sensation and positive psychological states, and these psychological response may have triggered the release of neurotransmitters resulting in l-DLPFC activation and EF enhancement.

Conversely, the participants grouped in the “Low feeling clear-headed” and “Groove-unfamiliar” clusters experienced no or negative effects of GR on EF and l-DLPFC activity. One potential inhibiting factor is low beat-processing ability in those individuals. It is possible that participants who have a low beat-processing ability were forced to pay extra attention to the beat while listening to the GR. This may have resulted not only in inducing failure to become entrained, but also in reduced mental resources, which limited attention, motivation, and cognitive performance. In the current experiment, the average scores for the beat-processing ability test among participants in both the “Low feeling clear-headed” and “Groove-unfamiliar” clusters were relatively low compared to the participants in the “Groove-familiar” cluster, but not significantly so. Since the beat alignment test used in the current study was a simple battery test to evaluate beat processing ability, further studies using battery tests with a higher sensitivity are needed to detect the influence of inhibiting factors.

This study has several limitations. First, widespread individual differences in psychological responses to the rhythm were demonstrated in the current results. Various potential factors such as musical training experience, music reward sensitivity, beat processing ability, familiarity with groove music/dance, body morphology and cultural background could influence psychological responses to the rhythm. Though more than 50 students participated in the current experiment, the sample size was insufficient for conducting sub-analyses to seek the effects of these potential influential factors. Future studies should plan to compare the effects between participants grouped by these potential influential factors. Second, in the auditory stimulus, we used rhythm with a low to medium degree of syncopation as the GR stimulus and a white-noise metronome as the control stimulus. We could control tempo, but could not control the type and number of sounds. Further studies are needed to try to detect the influence of other acoustic specifications by using different patterns for the groove rhythm (GR) and control stimuli. Third, in the measurement of the brain’s neural activation, the current study focused on only cortical, specifically the l-DLPFC, activity. We should use fMRI and PET to examine brain activity in broader and deeper regions that are involved with motor, reward, and cognitive systems, their networks, and released neurotransmitters.

In conclusion, listening to a rhythm with low to medium syncopation enhanced executive function (EF) and dorsolateral prefrontal cortex (l-DLPFC) activity in only groove-familiar participants, which supports our hypothesis. These results suggest that individual differences in psychological responses to GR are one of the key factors in predicting the effects of listening to GR on prefrontal EF. This study raises the potential that GR can enhance human cognitive performance like exercise.

 

Source: nature.com, Takemune Fukuie, Kazuya Suwabe, Satoshi Kawase, Takeshi Shimizu, Genta Ochi, Ryuta Kuwamizu, Yosuke Sakairi & Hideaki Soya

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