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Tag: National Institute of Neurological Disorders and Stroke (NINDS)

  • Flexible Nanoelectrodes Stimulate Brain with Precision

    Flexible Nanoelectrodes Stimulate Brain with Precision

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    Newswise — Traditional implantable medical devices intended for brain stimulation frequently possess a rigidity and bulkiness that is incongruous with one of the human body’s most supple and fragile tissues.

    In response to this issue, engineers at Rice University have created nanoelectrodes that are minimally invasive and exceptionally flexible. These nanoelectrodes have the potential to function as an implanted platform, enabling long-term, high-resolution stimulation therapy.

    As reported in Cell Reports, a study revealed that these minute implantable devices established stable and enduring tissue-electrode interfaces in rodents with minimal scarring or deterioration. The devices were capable of delivering electrical pulses that closely resembled neuronal signaling patterns and amplitudes, surpassing the capabilities of traditional intracortical electrodes.

    Due to their exceptional biocompatibility and precise spatiotemporal stimulus control, these devices have the potential to facilitate the advancement of novel brain stimulation therapies. These therapies, such as neuronal prostheses, could greatly benefit individuals with impaired sensory or motor functions.

    Lan Luan, a corresponding author on the study and an assistant professor of electrical and computer engineering, explained that the research paper utilizes imaging, behavioral, and histological methods to demonstrate the enhanced effectiveness of stimulation achieved by these tissue-integrated electrodes. The electrodes have the capability to administer precise and minute electrical pulses, thereby facilitating controlled neural activity excitation.

    The team of researchers successfully achieved a significant reduction in the required current for neuronal activation, surpassing an order of magnitude. This means that the electrical pulses delivered by the electrodes can be as subtle as a duration of a couple hundred microseconds and an amplitude of one or two microamps. Such precise and low-intensity stimulation holds great potential for advancing the field of brain stimulation therapies.

    The recently developed electrode design by the researchers at the Rice Neuroengineering Initiative marks a substantial advancement compared to traditional implantable electrodes utilized for treating conditions like Parkinson’s disease, epilepsy, and obsessive-compulsive disorder. Conventional electrodes often lead to adverse tissue reactions and unintended alterations in neural activity. The new electrode design aims to address these challenges and offers a promising solution for enhancing the effectiveness and safety of treatments for such neurological conditions.

    Chong Xie, a corresponding author of the study and an associate professor of electrical and computer engineering, stated that traditional electrodes are highly invasive in nature. These electrodes typically activate thousands or even millions of neurons simultaneously.

    “When all these neurons are stimulated simultaneously, their individual functions and coordination, which are supposed to follow specific patterns, get disrupted,” explained Chong Xie. “While this simultaneous stimulation may have the desired therapeutic effect in certain cases, it lacks the necessary precision and control, especially when it comes to encoding sensory information. To achieve more precise and effective outcomes, greater control over the stimuli is essential.”

    Xie drew a comparison between the stimulation provided by traditional electrodes and the disruptive impact of “blowing an airhorn in everyone’s ear or having a loudspeaker blaring” in a room filled with people. This analogy emphasizes the lack of specificity and precision in conventional electrode stimulation, which can lead to a generalized and disruptive effect on neural activity.

    “We used to have this very big loudspeaker, and now everyone has an earpiece,” he said.

    Xie drew a comparison between the stimulation provided by traditional electrodes and the disruptive impact of “blowing an airhorn in everyone’s ear or having a loudspeaker blaring” in a room filled with people. This analogy emphasizes the lack of specificity and precision in conventional electrode stimulation, which can lead to a generalized and disruptive effect on neural activity.

    The capacity to modify the frequency, duration, and intensity of the signals holds the potential for the advancement of innovative sensory prosthetic devices.

    Luan stated, “When a larger current is employed, neuron activation becomes more widespread and diffuse. However, we successfully reduced the current and demonstrated a significantly more focused activation. This achievement can pave the way for the development of higher-resolution stimulation devices.”

    Both Luan and Xie are integral members of the Rice Neuroengineering Initiative, and their respective laboratories are engaged in a collaborative effort to develop an implantable visual prosthetic device aimed at assisting visually impaired patients.

    Luan envisions a future where electrode arrays can be implanted to restore impaired sensory function. He highlights that the precision and specificity of neuron activation play a crucial role in generating accurate and precise sensations. Luan emphasizes that the more focused and deliberate the activation of neurons, the higher the level of precision in the generated sensation.

    Luan, who will be assuming the position of associate professor starting from July 1, expressed the significance of their electrode’s ultraflexible design in achieving enhanced tissue integration. They have published a series of research papers demonstrating the electrode’s capability to facilitate improved recording of brain activity over extended periods, yielding superior signal-to-noise ratios.

    The study has been led by Roy Lycke, a postdoctoral associate in electrical and computer engineering, and Robin Kim, a graduate student. Both Lycke and Kim have played crucial roles as lead authors in conducting the research.

    The National Institute of Neurological Disorders and Stroke (R01NS109361, U01 NS115588) and Rice internal funds supported the research.

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    Rice University

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  • Review strengthens evidence that repetitive head impacts can cause CTE

    Review strengthens evidence that repetitive head impacts can cause CTE

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    Newswise — (Boston)—During the past 17 years, there has been a remarkable increase in scientific research concerning chronic traumatic encephalopathy (CTE) with researchers at the BU CTE Center at the forefront. While some sports organizations like the National Hockey League and World Rugby still claim their sports do not cause CTE, a new review of the evidence by the world’s leading CTE expert strengthens the case that repetitive head impact (RHI) exposure is the chief risk factor for the condition.

    CTE became national news in the United States in 2007, but it wasn’t until 2016 that the National Institute of Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering (NINDS-NIBIB) criteria for the neuropathological diagnosis of CTE were published, and they were refined in 2021. Rare, isolated case studies reporting aberrant findings or using non-accepted diagnostic criteria have been disproportionately emphasized to cast doubt on the connection between RHI and CTE.

    In a review article in the journal Acta Neuropathologica, Ann McKee, MD, chief of neuropathology at VA Boston Healthcare System and director of the BU CTE Center, stresses that now over 600 CTE cases have been published in the literature from multiple international research groups. And of those over 600 cases, 97 percent have confirmed exposure to RHI, primarily through contact and collision sports. CTE has been diagnosed in amateur and professional athletes, including athletes from American, Canadian, and Australian football, rugby union, rugby league, soccer, ice hockey, bull-riding, wrestling, mixed-martial arts, and boxing.

    What’s more, 82 percent (14 of the 17) of the purported CTE cases that occurred in the absence of RHI, where up-to-date criteria were used, the study authors disclosed that families were never asked what sports the decedent played. 

    According to the researchers, despite global efforts to find CTE in the absence of contact sport participation or RHI exposure, it appears to be extraordinarily rare, if it exists at all. “In studies of community brain banks, CTE has been seen in 0 to 3 percent of cases, and where the information is available, positive cases were exposed to brain injuries or RHI. In contrast, CTE is the most common neurodegenerative disease diagnosis in contact and collision sport athletes in brain banks around the world. A strong dose response relationship is perhaps the strongest evidence that RHI is causing CTE in athletes,” she added.

    “The review presents the timeline for the development of neuropathological criteria for the diagnosis of CTE which was begun nearly 100 years ago by pathologist Harrison Martland who introduced the term “punch-drunk” to describe a neurological condition in prizefighters,” explained McKee, corresponding author of the study. The review chronologically describes the multiple studies conducted by independent, international groups investigating different populations that found CTE pathology in individuals with a history of RHI from various sources.”

    CTE is characterized by a distinctive molecular structural configuration of p-tau fibrils that is unlike the changes observed with aging, Alzheimer’s disease, or any other diseases caused by tau protein.

    Funding for this research was provided by the National Institute of Neurological Disorders and Stroke (U54NS115266; R01NS119651; U01 NS 086659), National Institute on Aging (P30AG13846; U19AG06875; R01AG062348; RF1AG057902; K01AG070326), Department of Veterans Affairs (101BX002466, 101BX004613, BX004349), the Nick and Lynn Buoniconti Foundation, Andlinger Foundation, National Football League (NFL) and World Wrestling Entertainment (WWE) through unrestricted gifts, the Mac Parkman Foundation, and the National Operating Committee on Safety for Sports Equipment (NOCSEA).

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    Boston University School of Medicine

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  • Spinal Cord Injury: Can Brain and Nerve Stimulation Restore Movement?

    Spinal Cord Injury: Can Brain and Nerve Stimulation Restore Movement?

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    Newswise — NEW YORK, NY–A nerve stimulation therapy developed at Columbia University Vagelos College of Physicians and Surgeons is showing promise in animal studies and may eventually allow people with spinal cord injuries to regain function of their arms.

    “The stimulation technique targets the nervous system connections spared by injury,” says Jason Carmel, MD, PhD, a neurologist at Columbia University and NewYork-Presbyterian who is leading the research, “enabling them to take over some of the lost function.”

    The findings were published in December in the journal Brain.

    A personal quest to develop treatments for people with paralysis

    In 1999, when Carmel was a second-year medical student at Columbia, his identical twin brother suffered a spinal cord injury, paralyzing him from the chest down and limiting the use of his hands.

    Carmel’s life changed that day, too. His brother’s injury ultimately led Carmel to become a neurologist and a neuroscientist, with the goal of developing new treatments to restore movement in people living with paralysis.

    In recent years, some high-profile studies of spinal cord electrical stimulation have allowed a few people with incomplete paralysis to begin to stand and take steps again.

    Carmel’s approach is different because it targets the arm and hand and because it pairs brain and spinal cord stimulation, with electrical stimulation of the brain followed by stimulation of the spinal cord. “When the two signals converge at the level of the spinal cord, within about 10 milliseconds of each other, we get the strongest effect,” he says, “and the combination appears to enable the remaining connections in the spinal cord to take control.”

    In his latest study, Carmel tested his technique—called spinal cord associative plasticity (SCAP)—on rats with moderate spinal cord injuries. Ten days after injury, the rats were randomized to receive 30 minutes of SCAP for 10 days or sham stimulation. At the end of the study period, rats that received SCAP targeted to their arms were significantly better at handling food, compared to those in the control group, and had near-normal reflexes.

    “The improvements in both function and physiology persisted for as long as they were measured, up to 50 days,” Carmel says.

    The findings suggest that SCAP causes the synapses (connections between neurons) or the neurons themselves to undergo lasting change. “The paired signals essentially mimic the normal sensory-motor integration that needs to come together to perform skilled movement,” says Carmel. 

    From mice to people

    If the same technique works in people with spinal cord injuries, patients could regain something else they lost in the injury: independence. Many spinal cord stimulation studies focus on walking, but “if you ask people with cervical spinal cord injury, which is the majority, what movement they want to get back, they say hand and arm function,” Carmel says. “Hand and arm function allows people to be more independent, like moving from a bed to a wheelchair or dressing and feeding themselves.”

    Carmel is now testing SCAP on spinal cord injury patients at Columbia, Weill Cornell, and the VA Bronx Healthcare System in a clinical trial sponsored by the National Institute of Neurological Disorders and Stroke. The stimulation will be done either during a clinically indicated surgery or noninvasively, using magnetic stimulation of brain and stimulation of the skin on the front and back of the neck. Both techniques are routinely performed in clinical settings and are known to be safe.

    In the trial, the researchers hope to learn more about how SCAP works and how the timing and strength of the signals affect motor responses in the fingers and hands. This would lay the groundwork for future trials to test the technique’s ability to meaningfully improve hand and arm function.

    Looking farther ahead, the researchers think that the approach could be used to improve movement and sensation in patients with lower-body paralysis.

    In the meantime, Jason Carmel’s twin is working, married, and raising twins of his own. “He has a full life, but I’m hoping we can get more function back for him and other people with similar injuries,” says Carmel.

     

    More information

    The study is titled “Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury.”

    Other contributors: Ajay Pal, HongGeun Park, Aditya Ramamurthy, Ahmet S. Asan, Thelma Bethea, and Meenu Johnkutty (all at Columbia).

    The study was funded by the National Institute of Neurological Disorders and Stroke (R01NS115470) and the Travis Roy Foundation.

    Jason Carmel is a co-inventor of a patent for the use of softening spinal electrodes. He also has equity in Backstop Neural, which seeks to commercialize the devices for humans. The authors declare no other competing financial interests.

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    Columbia University Irving Medical Center

    Columbia University Irving Medical Center (CUIMC) is a clinical, research, and educational campus located in New York City, and is one of the oldest academic medical centers in the United States. CUIMC is home to four professional colleges and schools (Vagelos College of Physicians and Surgeons, Mailman School of Public Health, College of Dental Medicine, and School of Nursing) that are global leaders in their fields. CUIMC is committed to providing inclusive and equitable health and medical education, scientific research, and patient care, and working together with our local upper Manhattan community—one of New York City’s most diverse neighborhoods. For more information, please visit cuimc.columbia.edu.  

     

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    Columbia University Irving Medical Center

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