New Brain Pathway Key to Movement Found in PD Patients, Study Reports

new brain pathway

Placing electrodes directly in the brains of people with Parkinson’s disease revealed a “hyperdirect” pathway between two regions of the brain responsible for movement and cognition, a study reported.

This pathway was shown to be important in being able to stop body movements once initiated. Modulating or controlling this pathway may be a therapeutic strategy for treating movement disorders such as Parkinson’s.

The study, “Prefrontal-Subthalamic Hyperdirect Pathway Modulates Movement Inhibition in Humans,” was published in the journal Neuron

Parkinson’s disease is characterized by a progressive loss of coordination and movement leading to involuntary tremors and other motor symptoms.

Stopping a body movement that has already been initiated is important for motor control, which is thought to be mediated by a pathway between two regions in the brain. The pathway connects the subthalamic nucleus (STN), which is involved in many complex motor and non-motor functions, and the inferior frontal gyrus (IFG), associated with cognition.

“This pathway is critical to controlling movement overall,” Witney Chen, a graduate student at the University of California, San Francisco (UCSF) and the study’s first author, said in a news story.

“We’re interested in understanding how the brain controls the ways we can stop movement because when this control isn’t functioning properly, it can result in movement disorders such as Parkinson’s,” Chen said.

“This is more than just being able to quickly stop your step into the street if you see oncoming traffic,” she added.

Evidence suggested that the STN-IFG pathway exists in animals. However, only indirect imaging studies have supported its importance in humans, and in the workings of Parkinson’s disease.

To explore this pathway, Chen and colleagues based at UCSF designed a study involving 21 Parkinson’s patients in which electrodes were placed directly in the brain in both the IFG and STN regions. The goal was to gather as much information as possible about this pathway in humans.

“It’s a wonderful opportunity to study the human brain as an intact system,” said Philip Starr, MD, PhD, co-director of the UCSF Surgical Movement Disorders Center and the study’s senior author.  “And fortunately, Parkinson’s patients are especially eager to volunteer. They’re often people who had normal lives for a long time, and now they have this disorder and they really want to contribute to understanding and treating it.”

“These experiments can really only be done well with invasive electrodes at both ends of the pathway,” Starr added.

The Parkinson’s patients enrolled in the study were already scheduled to have electrodes implanted in the STN region of the brain, a standard procedure for deep brain stimulation (DBS), often used on those with mid-stage disease. As there are no pain receptors in the brain, the participants are awake during surgery and can confirm the placement and function of the DBS implants with physicians. 

During the procedure, electrodes also were placed on the surface of the brain, about five centimeters (2 inches) from the DBS implants. Chen noted that these electrode could easily be removed after the experiments.

The team then recorded high-resolution electrical impulses focusing on location and time. They found the response to STN stimulation was detected very quickly (low latency) in the IFG region, which demonstrated a “hyperdirect” connection between these two parts of the brain. 

A second experiment was conducted to measure the ability to stop a body movement. Here, patients were shown either a right or left arrow on a screen as a “go” signal, to which they responded by pushing a respective right or left button in response. Randomly, they received a “stop” signal after the “go” signal and the time taken to stop movement was measured.

The results showed that the longer the IFG and STN signals were simultaneously activated — representing a higher synchronization between both regions — the faster the participants stopped their action, and that faster initiation of activity was found to be important for successful stopping. These findings, shown across all participants tested, demonstrated a direct synchronization between these two brain regions in movement control.

Although movement inhibition has been found to be impaired in people with Parkinson’s, the team did not find physiological factors or stopping behaviors to be associated with parkinsonian severity, as assessed by the Unified Parkinson’s Disease Rating Scale.

“Our study is the first to show that the hyperdirect circuit co-modulation is linked to stopping behaviors, which has broad implications for stimulation-based therapies to treat maladaptive movement inhibition,” the scientists concluded. 

“These findings may inform therapies to treat disorders featuring perturbed movement inhibition,” they added. 

The next step is to study the role of the IFG and STN pathway in more real-life settings using electrodes that can record brain activity over longer periods of time, the researchers said. 

“Using this technology, we can start to tease apart what this circuit is doing in real life when people are moving, talking, walking, playing music or sports or whatever they want to do,” Chen said. 

“We’re really pursuing these therapeutic aspects, because we think modulation in this circuit can translate to better clinical outcomes,” she concluded.

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Glassy Carbon Electrodes Safer Than Metal in MRIs, Study Suggests

glassy carbon electrodes

Implantable electrodes made of glassy carbon may be safer for use in MRI scans than traditional electrodes made of metal for people who undergo deep brain stimulation, a new study shows.

The study, “Glassy carbon microelectrodes minimize induced voltages, mechanical vibrations, and artifacts in magnetic resonance imaging,” was published in Microsystems & Nanoengineering.

In cases where Parkinson’s patients are not responding well to medication, deep brain stimulation (DBS) can be used to treat motor symptoms associated with this neurodegenerative disease. The treatment involves surgically implanting an electrode directly in the brain, then using that electrode to electrically stimulate specific brain regions.

Traditionally, electrodes used for DBS have been made of metal, most typically platinum. But metal electrodes pose a problem when a person needs to undergo an MRI scan. Such scans can be used to image the brain using powerful magnets, but those magnets can interact badly with metal electrodes.

Specifically, the electrodes can lead to large “white spots” on the MRI images themselves, which can limit the utility of the images. Plus, the magnetic fields generated in MRI can cause electrodes to vibrate, or they can generate electrical currents that make the electrode heat up. These circumstances run the risk of causing damage or irritation in the brain.

In the new study, researchers wondered if electrodes made of glassy carbon, instead of metal, would be resistant to these issues. Glassy carbon (GC) is basically a bunch of very thin layers of carbon pressed together.

The researchers previously had created GC-based electrodes designed for DBS, and in a previous study, they showed that these electrodes were more durable than traditional platinum ones.

“Inherently, the carbon thin-film material is homogenous—or one continuous material—so it has very few defective surfaces. Platinum has grains of metal which become the weak spots vulnerable to corrosion,” Sam Kassegne, PhD, a professor at San Diego State University (SDSU) and co-author of both studies, said in a press release.

The researchers tested their GC electrodes in an MRI; but, rather than using actual human brains, they implanted the electrodes in a substance sort of like Jell-O. The researchers demonstrated that, while the metal electrode created a bright white patch on the MRI images themselves, the CG was nearly invisible — suggesting that, in an actual brain, this type of electrode would interfere with imaging far less.

They measured the currents generated in these electrodes during an MRI scan, as well as how much they vibrated, and compared these measurements to similar measurements obtained using traditional metal probes.

They found that the current generated in the GC electrodes was about 10 times lower than that in the metal probes. Similarly, vibrations in the GC electrode were about 40 times weaker than those in the metal ones, Researchers noted, however, that “for both types of microelectrodes, the measurable forces were below the detection limit” — that is, the vibrations were very small for both, even if they were smaller for the GC electrode.

“Our lab testing shows that unlike the metal electrode, the glassy carbon electrode does not get magnetized by the MRI, so it won’t irritate the patient’s brain,” said Surabhi Nimbalkar, study co-author and doctoral candidate at SDSU.

Although the researchers noted that they did not directly assess heating of the electrodes, which may be an avenue for further study, they nonetheless concluded that “GC microelectrodes demonstrate superior behavior with respect to MR safety compared to [platinum]-based electrodes.”

“Since GC has recently been demonstrated to have a compelling advantage over other materials for neural stimulation (…), this MRI compatibility validated in this study offers an additional advantage for long-term in vivo use in clinical settings,” they wrote.

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Deep Brain Stimulation May Help Parkinson’s Patients Live Longer, Study Shows

Deep brain stimulation

Deep brain stimulation (DBS) may help extend the survival of patients with Parkinson’s disease, according to a new study by researchers at the Edward Hines, Jr. VA Hospital in Hines, Illinois.

“Overall, DBS surgery has been viewed quite positively by both patients and providers,” Dr. Frances Weaver, the study’s lead author, said in a press release.

“There is an immediate effect on patients who have DBS on their motor function — the dyskinesia [involuntary muscle movements] is either gone or greatly reduced. The patient can move around and do things they hadn’t been able to,” Weaver said.

The research, “Survival in patients with Parkinson’s disease after deep brain stimulation or medical management,” appeared in the journal Movement Disorders.

Deep brain stimulation is a treatment that uses a medical implant, similar to a pacemaker, that sends electrical impulses via electrodes to specific areas of the brain. The implant is placed under the collarbone or in the abdomen.

Previous studies showed that this treatment led to a significant long-term improvement in motor function. But whether it improves survival remained largely unknown.

To answer this question, researchers compared data from two groups of veterans with Parkinson’s disease — those who received DBS vs. those who did not. In total, researchers analyzed each group’s data, which was retrieved from the VA and Medicare from 2007 to 2013.

The results showed that those treated with DBS survived longer, on average, than those without the device – 6.3 years after the surgery versus 5.7 years, respectively.

The analysis compared patients who submitted to deep brain stimulation to matched controls (those who did not have the DBS surgery) for age and symptom severity. Researchers then measured patients’ survival from the date of surgery in both groups.

Besides the modest increase in survival, the quality of life also improved after deep brain stimulation, mainly because the Parkinson’s patients were better able to control their disease symptoms, like tremors and rigidity.

Other confounding factors could also contribute to the observed phenotype, researchers said. Patients who had DBS surgery are closely monitored and any additional conditions are likely identified and treated in a timely fashion, while the same conditions may remain unnoticed in patients without the surgery.

Researchers also noted that most of the patients in the study were men, so the findings are not immediately extended to female patients with Parkinson’s disease.

DBS is usually employed when other forms of therapy, primarily medication, stops working.

“The surgery may get patients back to where they were when the medication was effective. That is, DBS is typically as effective as the medication — if the medication was still working,” Weaver said.

Additional studies are needed to confirm if indeed deep brain stimulation extends Parkinson’s disease patients’ life expectancy. If so, another question that remains is how: Does it halt disease progression or does it have indirect effects, improving only Parkinson’s disease-related conditions or diseases?

More research will shed light on the mechanisms of deep brain stimulation and how it may modulate brain function.

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Source: Parkinson's News Today