Posts tagged movement disorders
Articles and news from the latest research reports.
Forget Smart Watches, ‘Smart Skin’ May Be the Next Big Thing in Wearable Computers
Parkinson’s patients could one day ditch their pills for a stretchy skin patch with a mind of its own. Using specialized sensors, the patch would monitor the wearer’s vital signs, beam the information to a doctor, and administer medication as needed. While such devices still face substantial obstacles before wide-scale implementation, two teams of researchers have announced innovations combining standard electronics with flexible materials that may bring the futuristic concept closer to reality.
Conventional electronics, such as those found in computers and smartphones, are built on stiff slabs of silicon. While durable, the design makes for bulky and uncomfortable wearable devices. Flexible electronics instead print circuits onto limber strips of silicone or plastic. The bendable base layers make devices twist and stretch when attached to the skin, but they are limited by a lack of key components such as batteries and processors that currently do not exist in flexible form.
Researchers from Seoul National University led by bioengineer Dae-Hyeong Kim have now developed a patch that automatically delivers medication to Parkinson’s patients. Parkinson’s disease is a neurological disorder that causes movement impairments such as hand tremors that require regular medication to suppress. Typically, patients take pills every few hours, leading to a spike in medication levels followed by a gradual decline that causes the tremors to return. The team’s skin patch instead supplies a series of smaller measured doses as needed by using a tremor-detecting sensor. Because the device needs to track the tremors over time, they utilized a newly invented memory format called resistive random-access memory to create the first flexible data storage for wearable devices. The new format can be used in a thin, low-power form, making it ideal for inclusion in wearable electronics.
Neurotransmitters resarch can promote better drugs for brain disorders
Although drugs have been developed that inhibit the imbalance of neurotransmitters in the brain – a condition which causes many brain disorders and nervous system diseases – the exact understanding of the mechanism by which these drugs work has not yet been fully explained.
Now, researchers at the Hebrew University of Jerusalem, using baker’s yeast as a model, have deciphered the mode by which the inhibitors affect the neurological transmission process and have even been able to manipulate it.
Their work, reported in a recent article in the Journal of Biological Chemistry, raises hopes that these insights could eventually guide clinical scientists to develop new and more effective drugs for brain disorders associated with neurotransmitter imbalance.
All of the basic tasks of our existence are executed by the brain – whether it is breathing, heartbeat, memory building or physical movements – which depend on the highly regulated and efficient release of neurotransmitters – chemicals that act as messengers enabling extremely rapid connections between the neurons in the brain.
When even one part of the everyday “conversation” between neighboring neurons breaks down, the results can be devastating. Many brain disorders and nervous system diseases, including Huntington’s disease, various motor dysfunctions and even Parkinson’s disease, have been linked to problems with neurotransmitter transport.
The neurotransmitters are stored in the neuron in small, bubble-like compartments, called vesicles, containing transport proteins that are responsible for the storage of the neurotransmitters into the vesicles.
The storage of certain neurotransmitters is controlled by what is called the vesicular monoamine transporter (VMAT), which is known to transport a variety of vital neurotransmitters, such as adrenaline, dopamine and serotonin.
In addition, it can also transport the detrimental MPP+, a neurotoxin involved in models of Parkinson’s disease.
A number of studies demonstrated the significance of VMAT as a target for drug therapy in a variety of pathologic states, such as high blood pressure, hyperkinetic movement disorders and Tourette syndrome.
Many of the drugs that target VMAT act as inhibitors, including the classical VMAT2 inhibitor, tetrabenazine. Tetrabenazine has long been used for the treatment of motor dysfunctions associated with Huntington’s disease and other movement disorders. However, the mechanism by which the drug affects the storage of neurotransmitters was not fully understood.
The Hebrew University study set out, therefore, to achieve an understanding of the basic biochemical mechanism underlying the VMAT reaction, with a view towards better controlling it through new drug designs.
The research was conducted by in the laboratory of Prof. Shimon Schuldiner of the Hebrew University’s Department of Biological Chemistry; Dr.Yelena Ugolev, postdoctoral fellow in the laboratory; and research students Tali Segal, Dana Yaffe and Yael Gros.
To identify protein sequences responsible for tetrabenazine binding, the Hebrew University scientists harnessed the power of yeast genetics along with the method of directed evolution.
Expressing the human protein VMAT in baker’s yeast cells confers them with the ability to grow in the presence of toxic substrates, such as neurotoxin MPP+. Directed evolution mimics natural evolution in the laboratory and is a method used in protein engineering.
By using rounds of random mutations targeted to the gene encoding the protein of interest, the proteins can be tuned to acquire new properties or to adapt to new functions or environment.
The study led to identification of important flexible domains (or regions) in the structure of the VMAT, responsible for producing optional rearrangements in tetrabenazine binding, and also enabling regulation of the velocity of the neurotransmitter transporter.
Utilizing these new, controllable adaptations could serve as a guide for clinical scientists to develop more efficient drugs for brain disorders associated with neurotransmitter imbalance, say the Hebrew University researchers.
(Source: eurekalert.org)
Study Finds Factors That May Cause Fluctuations in Deep Brain Stimulation Levels Over Time
Deep brain stimulation therapy blocks or modulates electrical signals in the brain to improve symptoms in patients suffering from movement disorders such as Parkinson’s disease, essential tremor and dystonia, but a new study suggests that several factors may cause electrical current to vary over time.
Led by Michele Tagliati, MD, director of Cedars-Sinai Medical Center’s Movement Disorders Program, the study identified variables that affect impedance – resistance in circuits that affect intensity and wavelength of electrical current. Doctors who specialize in programming DBS devices fine-tune voltage, frequency and other parameters for each patient; deviations from these settings may have the potential to alter patient outcomes.
“Deep brain stimulation devices are currently designed to deliver constant, steady voltage, and we believe consistency and reliability are critical in providing therapeutic stimulation. But we found that we cannot take impedance stability for granted over the long term,” said Tagliati, the senior author of a journal article that reveals the study’s findings.
“Doctors with experience in DBS management can easily make adjustments to compensate for these fluctuations, and future devices may do so automatically,” he added. “Although our study was not designed to link changes in impedance and voltage with clinical outcomes, we believe it is important for patients to have regular, ongoing clinic visits to be sure they receive a steady level of stimulation to prevent the emergence of side effects or the re-emergence of symptoms.”
Findings of the study – one of the largest of its kind and possibly the first to follow patients for up to five years – were published online ahead of print in Brain Stimulation. Researchers collected 2,851 impedance measurements in 94 patients over a period of six months to five years, evaluating fluctuations in individual patients and in individual electrodes. They looked at a variety of factors, including how long a patient had undergone treatment, the position of the implanted electrode, the side of the brain where the electrode was implanted, and even placement and function of contact positions along electrodes.
Medications usually are the first line of treatment for movement disorders, but if drugs fail to provide adequate relief or side effects are excessive, neurologists and neurosurgeons may supplement them with deep brain stimulation. Electrical leads are implanted in the brain, and an electrical pulse generator is placed near the collarbone. The device is then programmed with a remote, hand-held controller.
(Source: newswise.com)
Study finds brain-imaging technique can help diagnose movement disorders
A new University of Florida study suggests a promising brain-imaging technique has the potential to improve diagnoses for the millions of people with movement disorders such as Parkinson’s disease.
Utilizing the diffusion tensor imaging technique, as it is known, could allow clinicians to assess people earlier, leading to improved treatment interventions and therapies for patients.
The three-year study looked at 72 patients, each with a clinically defined movement disorder diagnosis. Using a technique called diffusion tensor imaging, the researchers successfully separated the patients into disorder groups with a high degree of accuracy.
The study is being published in the journal Movement Disorders.
“The purpose of this study is to identify markers in the brain that differentiate movement disorders which have clinical symptoms that overlap, making [the disorders] difficult to distinguish,” said David Vaillancourt, associate professor in the department of applied physiology and kinesiology and the study’s principal investigator.
“No other imaging, cerebrospinal fluid or blood marker has been this successful at differentiating these disorders,” he said. “The results are very promising.”
Movement disorders such as Parkinson’s disease, essential tremor, multiple system atrophy and progressive supranuclear palsy exhibit similar symptoms in the early stages, which can make it challenging to assign a specific diagnosis. Often, the original diagnosis changes as the disease progresses, Vaillancourt said.
Diffusion tensor imaging, known as DTI, is a non-invasive method that examines the diffusion of water molecules within the brain and can identify key areas that have been affected as a result of damage to gray matter and white matter in the brain. Vaillancourt and his team measured areas of the basal ganglia and cerebellum in individuals, and used a statistical approach to predict group classification. By asking different questions within the data and comparing different groups to one another, they were able to show distinct separation among disorders.
“Our goal was to use these measures to accurately predict the original disease classification,” Vaillancourt said. “The idea being that if a new patient came in with an unknown diagnosis, you might be able to apply this algorithm to that individual.
He compared the process to a cholesterol test.
“If you have high cholesterol, it raises your chances of developing heart disease in the future,” he said. “There are tests like those that give a probability or likelihood scenario of a particular disease group. We’re going a step further and trying to utilize information to predict the classification of specific tremor and Parkinsonian diseases.”
(Source: news.ufl.edu)
Newly understood circuits add finesse to nerve signals
An unusual kind of circuit fine-tunes the brain’s control over movement and incoming sensory information, and without relying on conventional nerve pathways, according to a study published this week in the journal Neuron.
Researchers at the University of Alabama at Birmingham (UAB) discovered new details of a mechanism operating in the cerebellum, the brain region that processes nerve signals coming in from the spinal cord and cortex.
“Our results explain a second layer of nerve signal transmission that depends, not on whether a nerve cell is wired into a defined signaling pathway circuit, but instead on how close it is to the pathway,” said Jacques Wadiche, Ph.D., assistant professor in the Department of Neurobiology within the UAB School of Medicine, investigator in the Evelyn McKnight Brain Institute at UAB and senior study author. “It has become clear that this kind of nerve circuit is intimately linked with autism and certain movement disorders, and we hope the mechanisms detailed here contribute to the design of new treatments.”
Beyond nerve pathways
Nerve cells are known to occur in defined pathways that transmit messages in one direction. This pathway-specific view of nerve signaling has been reinforced by high-tech imaging studies yielding detailed connectivity maps. Along these lines, the Obama Administration will soon ask Congress for $100 million in research funding to further improve such maps.
Within nerve pathways, each nerve cell sends an electric pulse down an extension of itself called an axon until it reaches a synapse, a gap between itself and the next cell in line. When it reaches an axon’s end, the pulse triggers the release of chemicals called neurotransmitters that float across the gap, where they either cause the downstream nerve cell to “fire” and pass on the message, or stop the message. In this way, each synapse between nerve cells in a pathway “decides” whether or not a message continues on.
In recent years, studies have found that neurotransmitters also spill into tissue surrounding axons in a type signaling not restricted to synaptic connections. With the term itself implying a mess, “spillover” was thought to degrade the capacity of nerve cells to precisely pass on signals.
The current study adds to recent evidence arguing that spillover may instead enhance message transmission, with the results revolving around three nerve cell types in the cerebellum: climbing fibers, Purkinje cells and interneurons.
Climbing fibers, which carry information from the brainstem into the cerebellum, play key roles in motor timing and sensory processing. Within these fibers, nerve cells release the excitatory neurotransmitter glutamate into synapses that then strive to pass messages deeper into the cerebellum. Purkinje cells are paired with climbing fibers and intent on inhibiting their signals.
When excited by glutamate from climbing fibers at one end, Purkinje cells release another neurotransmitter called GABA at their downstream synapse to stop the message. An excitatory signal triggers an inhibitory one as a counter-balance, a form of feedback critical to the function of the central nervous system. Lack of inhibition, for instance, causes circuits to seize, seizures and the death of Purkinje cells, the latter of which has been linked by post mortem studies to a higher incidence of autism spectrum disorders.
Previously, researchers thought that incoming signals from climbing fibers caused a single, strong response in the cerebellum: the activation of Purkinje cells that released GABA. The current study argues that such signals also trigger the firing of interneurons, nearby inhibitory middlemen that connect sets of nerve cells.
Interneurons within, and outside of, the glutamate spill zone around climbing fibers may have different effects on the other interneurons and Purkinje cells they connect to, according to the current finding. The interactions either inhibit or excite many Purkinje cells surrounding an active climbing fiber and refine its messages in a feedback system more sophisticated than once thought.
Glutamate has its effect by fitting into AMPA and NMDA receptor proteins, like a key into a lock, on the surfaces of nerve cells it signals to. The consensus has been that glutamate receptors occur only within synapses. Finding them on nerve cells outside of synapse-defined pathways represents “a fundamental shift in understanding,” said Wadiche, and may result in longer-lasting inhibition within key signaling pathways.
“A 2007 study published in Nature Neuroscience found that many climbing fibers signal to interneurons in the outer layer of the cerebellum outside nerve pathways and exclusively through glutamate spillover,” said Luke Coddington, a graduate student in Wadiche’s lab and study author. “Our team built on that observation to show how spillover affects the function of interneurons, Purkinje cells, and ultimately, the entire cerebellum. Spillover-mediated signaling recruits local microcircuits to extend the reach and finesse of climbing fiber signaling.”