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Saturday, May 17, 2014

An active role played by the motor cortex in learning movement patterns - Medical News Today

Wednesday 7 May 2014 - 1am PST
Wed 7 May 2014 - 1am PST



 Tennis Player


 

Piano Player

Skilled motor movements of the sort tennis players employ while serving a tennis ball or pianists use in playing a concerto, require precise interactions between the motor cortex and the rest of the brain. Neuroscientists had long assumed that the motor cortex functioned something like a piano keyboard.

"Every time you wanted to hear a specific note, there was a specific key to press," says Andrew Peters, a neurobiologist at UC San Diego's Center for Neural Circuits and Behavior. "In other words, every specific movement of a muscle required the activation of specific cells in the motor cortex because the main job of the motor cortex was thought to be to listen to the rest of the cortex and press the keys it's directed to press."

But in a study published in the advance online publication of the journal Nature, Peters, the first author of the paper, and his colleagues found that the motor cortex itself plays an active role in learning new motor movements. In a series of experiments using mice, the researchers showed in detail how those movements are learned over time.

Mouse Motor Cortex
Cells in the motor cortex of mice display regions in which the neurons are active (in green) and regions in which neuron firing is inhibited (in red).
Credit: UC San Diego
"Our finding that the relationship between body movements and the activity of the part of the cortex closest to the muscles is profoundly plastic and shaped by learning provides a better picture of this process," says Takaki Komiyama, an assistant professor of biology at UC San Diego who headed the research team. "That's important, because elucidating brain plasticity during learning could lead to new avenues for treating learning and movement disorders, including Parkinson's disease."

With Simon Chen, another UC San Diego neurobiologist, the researchers monitored the activity of neurons in the motor cortex over a period of two weeks while mice learned to press a lever in a specific way with their front limbs to receive a reward.

"What we saw was that during learning, different patterns of activity - which cells are active, when they're active - were evident in the motor cortex," says Peters. "This ends up translating to different patterns of activity even for similar movements. Once the animal has learned the movement, similar movements are then accompanied by consistent activity. This consistent activity moreover is totally new to the animal: it wasn't used early in learning even with movements that were similar to the later movement."

"Early on," Peters says, "the animals will occasionally make movements that look like the expert movements they make after learning. The patterns of brain activity that accompany those similar early and late movements are actually completely different though. Over the course of learning, the animal generates a whole new set of activity in the motor cortex to make that movement. In the piano keyboard analogy, that's like using one key to make a note early on, but a different key to make the same note later."
An active role played by the motor cortex in learning movement patterns - Medical News Today


Friday, May 16, 2014

Electrical stimulation of dopamine neurons alters human learning, offers potential for rehabilitation after injury or addictive behaviors - Medical News Today






Stimulation of a certain population of neurons within the brain can alter the learning process, according to a team of neuroscientists and neurosurgeons at the University of Pennsylvania. A report in the Journal of Neuroscience describes for the first time that human learning can be modified by stimulation of dopamine-containing neurons in a deep brain structure known as the substantia nigra. Researchers suggest that the stimulation may have altered learning by biasing individuals to repeat physical actions that resulted in reward.

"Stimulating the substantia nigra as participants received a reward led them to repeat the action that preceded the reward, suggesting that this brain region plays an important role in modulating action-based associative learning," said co-senior author Michael Kahana, PhD, professor of Psychology in Penn's School of Arts and Sciences.

Eleven study participants were all undergoing deep brain stimulation (DBS) treatment for Parkinson's disease. During an awake portion of the procedure, participants played a computer game where they chose between pairs of objects that carried different reward rates (like choosing between rigged slot machines in a casino). The objects were displayed on a computer screen and participants made selections by pressing buttons on hand-held controllers. When they got a reward, they were shown a green screen and heard a sound of a cash register (as they might in a casino). Participants were not told which objects were more likely to yield reward, but that their task was to figure out which ones were "good" options based on trial and error.

When stimulation was provided in the substantia nigra following reward, participants tended to repeat the button press that resulted in a reward. This was the case even when the rewarded object was no longer associated with that button press, resulting in poorer performance on the game when stimulation was given (48 percent accuracy), compared to when stimulation was not given (67 percent).

"While we've suspected, based on previous studies in animal models, that these dopaminergic neurons in the substainia nigra - play an important role in reward learning, this is the first study to demonstrate in humans that electrical stimulation near these neurons can modify the learning process," said the study's co-senior author Gordon Baltuch, MD, PhD, professor of Neurosurgery in the Perelman School of Medicine at the University of Pennsylvania. "This result also has possible clinical implications through modulating pathological reward-based learning, for conditions such as substance abuse or problem gambling, or enhancing the rehabilitation process in patients with neurological deficits."


Electrical stimulation of dopamine neurons alters human learning, offers potential for rehabilitation after injury or addictive behaviors - Medical News Today

Wednesday, May 14, 2014

International Stem Cell Corporation Announces Positive Parkinson's Disease Data

Tuesday April 29, 2014

Wall Street Journal Online - International Stem Cell Corporation (OTCQB: ISCO) (www.internationalstemcell.com), a California-based biotechnology company developing novel stem cell-based therapies and biomedical products announced today that some behavioral improvements have been observed after six months in the pre-clinical non-human primate (NHP) study of Parkinson's disease (PD). The detailed behavioral data will be presented at the 66th American Academy of Neurology Annual Meeting in Philadelphia.
"It is encouraging to see these behavioral scores trending in the right direction as it means that the implanted cells may be having a positive impact on the disease symptoms," said Professor D. Eugene Redmond Jr. MD, of Yale University Medical School and the study's supervisor. "The rating scores are equivalent to components of the UPDRS which is widely used in research to evaluate Parkinson's patients. The Parkison's score is known to correlate very highly with brain dopamine concentrations."
The study consists of 18 primates, all exposed to the neurotoxin, MPTP, divided into three cohorts, a sham treated group and two treatment groups receiving different doses of human neural stem cells (hPNSC) derived from ISCO's proprietary parthenogenetic stem cell line. All of the groups had matching levels of parkinsonism and functional disability prior to the cell injections. The 6 months data showed that the healthy behavior scores of the treatment group increased 170% while that of the placebo group increased by 58%. In addition, one of the treatment groups demonstrated a significant improvement in the main Parkinson's rating score of 63% (p < 0.05) while there was no significant improvement in the control group. The changes in these scores are particularly noteworthy as it signifies a greater reduction in the severity of the symptoms in the treatment group compared with the control group. A more detailed update will be presented once the histopathology and biodistribution analysis of the tissue has been completed.
Dr. Ruslan Semechkin ISCO's Chief Scientific Officer commented: "The results of this interim analysis are very promising. This study provides information about how our human neural stem cells, derived from our parthenogenetic stem cells, behave in a diseased brain and how the diseased tissue responds and is a critical part of our planned IND submission."
About International Stem Cell Corporation
International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells (hpSCs) and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs) hence avoiding ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenetic, homozygous stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals of differing genders, ages and racial background with minimal immune rejection after transplantation. hpSCs offer the potential to create the first true stem cell bank, UniStemCell(TM). ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology (www.lifelinecelltech.com), and stem cell-based skin care products through its subsidiary Lifeline Skin Care (www.lifelineskincare.com). More information is available at www.internationalstemcell.com.
According to the Parkinson's Disease Foundation, an estimated seven to 10 million people worldwide live with PD, with as many as one million of those in the United States alone, more than the combined total of people diagnosed with multiple sclerosis, muscular distrophy, and Lou Gehrig's disease. The total direct and indirect cost of Parkinson's disease is estimated to be nearly $25 billion per year in the United States alone.
ISCO's Parkinson's disease program uses human parthenogenetic neural stem cells (hPNSC), a novel therapeutic cellular product derived from the company's proprietary histocompatible human pluripotent stem cells. hPNSC are self-renewing multipotent cells that are precursors for the major cells of the central nervous system. The ability of hPNSC to (i) differentiate into dopaminergic (DA) neurons and (ii) express neurotrophic factors such as glial derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) to protect the nigrostriatal system, offers a new opportunity for the treatment of Parkinson's disease, especially in cases where current small molecule approaches fail to adequately control the symptoms.
(29 April 2014). Wall Street Journal Online. International Stem Cell Corporation Announces Positive Parkinson's Disease Datahttp://online.wsj.com/article/PR-CO-20140429-909787.html

Exenatide has Potential as a Disease Modifying Agent in Parkinson's Disease

Tuesday May 06, 2014

Medical Xpress - A follow-up study of patients with Parkinson's disease (PD) who participated in an earlier "proof of concept" clinical trial using exenatide showed that improvements persisted twelve months after discontinuing exenatide therapy. These data provide strong encouragement for the further study of this drug in patients with PD, report researchers in the Journal of Parkinson's Disease.
Several recent discoveries have highlighted common cellular pathways that potentially relate neurodegenerative processes with abnormal mitochondrial function and abnormal glucose metabolism.
Exenatide, a glucagon-like peptide-1 agonist (GLP-1 agonist) medication marketed as Byetta® and Bydureon® and used in the treatment of insulin resistance in patients with Type 2 diabetes, has been proposed as a disease modifying drug in PD. Earlier studies had shown that  is neuroprotective and promotes functionally beneficial neuroplasticity in animal models of neurodegeneration. Furthermore, exenatide has a favorable safety profile, with only relatively mild gastrointestinal side effects (including nausea and weight loss) as frequent adverse events.
In an earlier "proof of concept" randomized controlled trial published in May 2013, participants were randomized to either self-administer exenatide in addition to their regular PD medications or to act as controls, i.e., receive their conventional PD treatment only. All of the participants had moderate severity PD. In total, 44 patients (20 in the exenatide group and 24 controls) completed the trial. After 12 months the results showed significant and clinically meaningful differences in both motor and cognitive symptoms between those patients receiving exenatide and the controls. At 14 months, when the patients had discontinued exenatide for two months, the exenatide-treated and control groups still differed from each other. The authors concluded that the study supported potential disease-modifying benefits of exenatide in PD, while acknowledging the lack of a placebo arm.
All of the participants took part in a repeat assessment 12 months after the trial ended. The motor and cognitive advantages persisted in the exenatide group. Compared with the control group, those in the exenatide group had an advantage of 5.6 when using the blinded MDS-UPDRS motor subscale and 5.3 points on the Mattis Dementia Rating scale.
"We found that patients on exenatide appeared essentially unchanged throughout and beyond the trial period, while the control group had the expected rate of gradual decline in movement and cognitive ability," comments senior investigator Thomas Foltynie, MRCP, PhD, of the Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK.
The investigators did not find evidence in their data to suggest that glucose tolerance is different in PD patients who received exenatide for 12 months.
"Aside from the changes in MDS-UPDRS scores, there was also persistent divergence in cognitive performance between the groups, with significant differences which were sustained along the trial period, far beyond the 12-month period of drug exposure," says Foltynie. "These data provide continued support for formal double blind trials of GLP-1 agonists as disease modifying drugs in PD."
"The present study could represent a milestone if future controlled trials provide evidence supporting a disease-modifying effect of exenatide and could lead to a revolution in PD therapy," comment Tanya Simuni, MD, of Northwestern University Feinberg School of Medicine, Chicago, and Patrik Brundin, MD, PhD, of the Van Andel Research Institute, Grand Rapids, MI. Writing in the same issue, they warn however that: "Notwithstanding the promising nature of the results, it has to be emphasized that placebo effects can be highly significant and long-standing in PD. Therefore one should not jump to premature conclusions, While placebo effects ought to have diminished 12 months after drug withdrawal so that the exenatide-treated and control groups no longer differed, a lingering placebo effect cannot be excluded."
Tom Isaacs, Co-founder and President of The Cure Parkinson's Trust which funded the follow-up study, says: "Although we have to remain cautious on the estimation of these results, we are encouraged by the findings. This is the first time that I have come across a program that has the potential to make an enduring change for Parkinson's  and we are excited by the potential of this scientific research."
(6 May 2014). Medical Express. Exenatide has potential as a disease modifying agent in Parkinson's disease. http://medicalxpress.com/news/2014-05-exenatide-potential-disease-agent-parkinson.html

Sleep in Parkinson's Disease With and Without Deep Brain Stimulation

Tuesday May 06, 2014

PR Newswire - 
New findings from The Parkinson Alliance (PA) survey entitled "Sleep in Parkinson's Disease With and Without Deep Brain Stimulation," show that sleep disturbance is highly prevalent in Parkinson's disease (PD), and deep brain stimulation therapy (DBS) may benefit sleep quality and duration. Given that sleep disturbance is a significant problem for people with PD--with health, social and psychological implications, PA conducted a survey related to sleep; 1,247 individuals with Parkinson's participated, including 353 participants who underwent DBS and 894 individuals without DBS.
The majority of participants in this study reported significant sleep disturbance. After controlling for age and disease duration, individuals who have DBS reported less night-time sleep disturbance specifically related to motor symptoms and other PD symptoms. Additionally, the individuals who had DBS reported longer duration of consecutive hours of night-time sleep as compared to the individuals who did not have DBS.
"This research conducted by The Parkinson Alliance highlights the prevalence of sleep disturbance across age and disease duration for individuals with PD. This study has a large number of participants, giving a glimpse into the pervasive nature of sleep disturbance for individuals with PD, further reinforcing the importance of assessing non-motor symptoms in this population. Importantly, this report gives an understanding about contributing factors to sleep disturbance and thorough and practical recommendations that may help improve sleep in individuals with PD," said Jeffrey Wertheimer, Ph.D., clinical neuropsychologist and Chief Research Consultant for The Parkinson Alliance. Wertheimer adds, "Sleep disturbance is often under-assessed and undertreated. Once individuals with PD and their treatment providers have a better understanding about the contributing factors to poor sleep, intervention can be initiated. Moreover, following a proper assessment of sleep disturbance, numerous techniques can be initiated, including implementation of good sleep hygiene, behavioral intervention (modifying behavior to assist with improving sleep), medications to facilitate sleep, and/or specialized sleep devices, such as CPAP (continuous positive airway pressure) or BiPAP (bilevel positive airway pressure) machines."
Baroni, Nastassia (30 April 2014). NewsFeeds. Sleep in Parkinson's Disease With and Without Deep Brain Stimulation. http://www.digitaljournal.com/pr/1898699

Sunday, May 11, 2014

Parkinson Power Overcome the Overwhelming


Parkinson Power has uploaded Parkinson Power Overcome the Overwhelming
Parkinson Power Overcome the Overwhelming
Parkinson Power

Jean Hubble, MD talking about APOKYN for the treatment of Parkinson's

Parkinson Power has uploaded Jean Hubble, MD talking about APOKYN for the treatment of Parkinson's
Jean Hubble, MD talking about APOKYN for the treatment of Parkinson's
Parkinson Power