New Imaging Application for Parkinson’s
Larry H. Bernstein, Md, FCAP, Curator
LPBI
Brain imaging technology offers new approach for studying Parkinsonian syndromes
The BioOptics World take on this story:
A newly developed portable device that employs functional near-infrared (fNIR) spectroscopy (a light-based technique to monitor changes in blood oxygenation in the brain) can identify differences in brain activation patterns associated with postural stability in people with Parkinson’s disease and healthy adults. The development allows scientists to better understand the role of the brain’s prefrontal cortex during standing and walking.
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Parkinson’s disease is a neurological disorder that arises when brain cells that control movement die, leaving many patients in the late stages of the disease unable to take a few steps before falling. Parkinsonian syndromes, which are common in older adults, are conditions that do not rise to a Parkinson’s diagnosis but encompass many symptoms of the disease, like rigidity, tremor and difficulty walking.
Past attempts to compare brain activity and stability in people with Parkinsonian syndromes have been limited, because neuroimaging tools could only be used when a study participant was lying flat, rather than walking or standing. In these cases, the person undergoing the brain scan could only imagine that he or she was performing the tasks.
A portable system created by researchers in Drexel’s School of Biomedical Engineering and Health Systems overcomes this challenge. It has allowed scientists, for the first time, to better understand the role of the brain’s prefrontal cortex during standing and walking.
The device employs functional near-infrared, or fNIR, spectroscopy, which uses light to monitor changes in blood oxygenation in the brain as individuals perform tasks, take tests or receive stimulation. The prefrontal cortex is the area responsible for higher-level processing, such as memory, attention, problem solving and decision-making. When a person is learning a new skill, for instance, neural activity is greater in this region.
Unlike fMRI (functional magnetic resonance imaging), the fNIR system is fully portable: Participants wear a headband, allowing them to talk and move around while a computer collects data in real time.
“Postural instability is a major risk factor for older adults. If we can monitor the cognitive component of staying balanced, then this could eventually lead to better treatment options for people with Parkinsonian syndromes or even Parkinson’s disease,” said Meltem Izzetoglu, PhD, an assistant research professor of biomedical engineering at Drexel who co-authored the study.
Researchers at Albert Einstein College of Medicine used the fNIR technology to compare 126 healthy adults to 117 individuals with mild Parkinson’s symptoms and 26 with more severe symptoms. While wearing the fNIR headband, the participants were asked to stand and look straight ahead while counting for 10 seconds. They then walked on a mat that captured their gait speed, pace and stride length. The fNIR system recorded their brain oxygen levels during the entire testing period.
The researchers found that those with Parkinsonian symptoms demonstrated significantly higher prefrontal oxygenation levels to maintain stability when standing than participants with mild and no symptoms.
“In fact, brain activity in the frontal brain region was nearly twice as large,” said Jeannette R. Mahoney, PhD, assistant professor of neurology at Einstein and the study’s lead author.
“This initial study allowed us to measure brain activity in real-time, in a realistic setting. It shows that there are indeed differences in the prefrontal cortex of healthy and Parkinsonian syndrome patients, and those differences relate to their performance in maintaining stability while standing,” Izzetoglu said. “It opens up new fields of research.”
In an upcoming clinical trial, the researchers will use a computerized cognitive training program and the fNIR system to identify how cognitive training affects brain activation during walking.
The portable technology could aid in diagnosing Parkinsonian syndromes or developing interventions.
“Our goal is to be able to intervene with Parkinsonian symptoms and develop novel remediation in the not-so-distant future to improve elders’ quality of life,” Mahoney said.
Jeannette R. Mahoney, Roee Holtzer, Meltem Izzetoglu, Vance Zemon, Joe Verghese, Gilles Allali. The role of prefrontal cortex during postural control in Parkinsonian syndromes a functional near-infrared spectroscopy study. Brain Research, 2015; DOI:10.1016/j.brainres.2015.10.053
- August 25, 2011 Source: Northwestern Memorial Hospital
- Summary:
- Physicians now have an objective test to evaluate patients for Parkinsonian syndromes, such as Parkinson’s disease. DaTscan™ is the only FDA-approved imaging agent for assessment of movement disorders. Until now, there were no definitive tests to identify the disease, forcing physicians to rely on clinical examinations to make a diagnosis. This technology allows doctors to differentiate Parkinson’s from other movement disorders.
Until now, there were no definitive tests to identify the disease, forcing physicians to rely on clinical examinations to make a diagnosis. This technology allows doctors to differentiate Parkinson’s from other movement disorders.
“The scan by itself does not make the diagnosis of Parkinson’s but it allows us to identify patients who have loss of dopamine, the major chemical responsible for the symptoms, from those who have no dopamine deficiency,” said Tanya Simuni, MD, a neurologist at Northwestern Memorial and director of Northwestern’s Parkinson’s Disease and Movement Disorders Center. “This is a very important step in being able to accurately identify and treat movement disorders and hopefully allow us to better understand these diseases over time.”
Parkinson’s disease is a neurodegenerative disorder that afflicts nearly 1.5 million Americans, with an additional 50,000 to 60,000 new cases identified each year. People with Parkinson’s lack dopamine in the brain, which leads to tremor, slowness of movement, muscle stiffness and balance problems. Clinical examinations, particularly early in the disease when symptoms are slight, can be inconclusive or lead to misdiagnosis of another movement disorder, such as essential tremor, which share similar symptoms to Parkinson’s, but require different treatment.
Developed by GE Healthcare, DaTscan is a substance used to detect the presence of dopamine transporters (DaT) in the brain. A patient is injected with the contrast agent and then undergoes a single-photon emission computed tomography (SPECT) scan. The test captures detailed pictures of the brain’s dopamine system and can provide visual evidence of the presence of dopamine transporters. Scans of patients with Parkinson’s disease or another parkinsonian syndrome will show very low dopamine levels. A SPECT scan examines brain function, rather than structure, and can show change in the brain’s chemistry.
“In Parkinson’s patients the brain’s anatomy remains largely normal, unlike other conditions such as stroke, where damage to the brain is visible,” explained Simuni, who is also an associate professor of neurology at Northwestern University Feinberg School of Medicine. “DaTscan attaches to dopamine neurons which illuminate on the SPECT scan; the more light areas that exist, the more healthy dopamine brain cells remain. If the areas of the brain that should show dopamine remain dark, it may indicate the patient has some type of parkinsonian syndrome.”
An accurate clinical diagnosis for patients with neurodegenerative movement disorders, such as Parkinson’s, can take up to six years. While symptoms often mimic Parkinson’s, other movement disorders, such as essential tremor, occur in different areas of the brain and do not involve the dopamine system.
“Even though they may appear similar, other movement disorders require different management. DaTscan allows us to confirm our diagnosis earlier and start the correct course of treatment sooner,” said Simuni. “We are hopeful that this will lead to improved quality of life for these patients with better long term outcomes, as well as protection from unnecessary treatments initiated because of misdiagnosis.”
While Simuni does not believe it is necessary for every patient to confirm their Parkinson’s diagnosis with DaTscan, she does see it as a valuable tool for patients with uncertain syndromes, or those who have not responded to treatment. She also sees it as a means for improving Parkinson’s research by ensuring those enrolled in studies actually have the disease. DaTscan is already being used by the Michael J. Fox Foundation for its landmark biomarkers study, the Parkinson’s Progression Markers Initiative (PPMI), to validate that the subjects have Parkinson’s disease. Northwestern is one of the 14 U.S. medical centers enrolling for the PPMI, which is among the first clinical trials using DaTscan in this way.
“Currently, we are not able to say with certainty that those enrolled in Parkinson’s studies have the disease,” said Simuni. “With the addition of DaTscan, we can be much more confident in the status of research subjects in both the control and experimental groups. By having a better understanding of these populations, we should be able to have clearer outcomes and hopefully that will translate sooner into treatments and eventually a cure.”
Researchers are also hopeful that DaTscan will prove to be useful in following the progression of Parkinson’s throughout a patient’s lifetime. “The disease is clinically measured at certain points of time to help physicians understand its development,” said Simuni. “A lot of questions about how Parkinson’s disease progresses can be answered if DaTscan is able to show us changes in the brain’s chemistry over time.”
- November 1, 2011 National Institute for Physiological Sciences
- Summary: Scientists have shown that the ‘oscillatory’ nature of electrical signals in subcortical nuclei, the basal ganglia, causes severe motor deficits in Parkinson’s disease, by disturbing the information flow of motor commands.
The research group headed by Professor Atsushi Nambu (The National Institute for Physiological Sciences) and Professor Masahiko Takada (Primate Research Institute,Kyoto University) has shown that the ‘oscillatory’ nature of electrical signals in subcortical nuclei, the basal ganglia, causes severe motor deficits in Parkinson’s disease, by disturbing the information flow of motor commands. The group also found that chemical inactivation of the subthalamic nucleus (a structure of the basal ganglia) in parkinsonian monkeys improved the motor impairments by reducing the ‘oscillations.’
The results of this study were reported in European Journal of Neuroscience,November 2011 issue.
A member of the research group, Assistant Professor Yoshihisa Tachibana, succeeded to record electrical signals in monkey basal ganglia neurons under unanesthetized conditions. The group found that neurons in the parkinsonian basal ganglia showed abnormal ‘oscillatory’ activity, which was rarely seen in normal subjects. The abnormal rhythm was completely eliminated by systemic administration of a dopamine precursor (L-DOPA), which is clinically used for human parkinsonian patients. The group considered that loss of dopamine induced the ‘oscillations’ in the basal ganglia and that the following disturbances in information flow of motor commands impaired motor performances.
Abnormal neuronal oscillations were already reported in parkinsonian patients and animal models, but this report has provided the direct evidence that ‘oscillations’ are associated with motor abnormalities. Moreover, it was also shown that the injection of a chemical inhibitor, muscimol, into the subthalamic nucleus silenced the oscillatory signals, and eventually reversed parkinsonian motor signs.
Professor Nambu claims, “By investigating the ‘oscillatory’ nature of electrical signals in the basal ganglia, we can advance our understanding of the pathophysiology of Parkinson’s disease. We improved motor deficits by means of infusion of the chemical inhibitor (muscimol) into the subthalamic nucleus to silence the ‘oscillatory’ signals in the brain structure. This may provide us important clues to developing new treatments for Parkinson’s disease.”
This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Japan Intractable Diseases Research Foundation and Hori Information Science Promotion Foundation to Y. Tachibana and A. Nambu, and NIH grants (NS-47085 and NS-57236) to H. Kita.
Yoshihisa Tachibana, Hirokazu Iwamuro, Hitoshi Kita, Masahiko Takada, Atsushi Nambu. Subthalamo-pallidal interactions underlying parkinsonian neuronal oscillations in the primate basal ganglia.European Journal of Neuroscience, 2011; 34 (9): 1470 DOI:10.1111/j.1460-9568.2011.07865.x
- Summary:
- It is possible to tell who a person is thinking about by analyzing images of his or her brain. Our mental models of people produce unique patterns of brain activation, which can be detected using advanced imaging techniques according to a new study.
“When we looked at our data, we were shocked that we could successfully decode who our participants were thinking about based on their brain activity,” said Spreng, assistant professor of human development in Cornell’s College of Human Ecology.
Understanding and predicting the behavior of others is a key to successfully navigating the social world, yet little is known about how the brain actually models the enduring personality traits that may drive others’ behavior, the authors say. Such ability allows us to anticipate how someone will act in a situation that may not have happened before.
To learn more, the researchers asked 19 young adults to learn about the personalities of four people who differed on key personality traits. Participants were given different scenarios (i.e. sitting on a bus when an elderly person gets on and there are no seats) and asked to imagine how a specified person would respond. During the task, their brains were scanned using functional magnetic resonance imaging (fMRI), which measures brain activity by detecting changes in blood flow.
They found that different patterns of brain activity in the medial prefrontal cortex (mPFC) were associated with each of the four different personalities. In other words, which person was being imagined could be accurately identified based solely on the brain activation pattern.
The results suggest that the brain codes the personality traits of others in distinct brain regions and this information is integrated in the medial prefrontal cortex (mPFC) to produce an overall personality model used to plan social interactions, the authors say.
The study, “Imagine All the People: How the Brain Creates and Uses Personality Models to Predict Behavior,” published online March 5 in the journal Cerebral Cortex and was coauthored by Demis Hassabis, University College London, Andrie Rusu, Vrije Univesiteit, Clifford Robbins, Harvard University, Raymond Mar, York University, and Daniel L. Schacter, Harvard University
Demis Hassabis, R. Nathan Spreng, Andrei A. Rusu, Clifford A. Robbins, Raymond A. Mar, and Daniel L. Schacter. Imagine All the People: How the Brain Creates and Uses Personality Models to Predict Behavior.Cerebral Cortex, 2013; DOI: 10.1093/cercor/bht042
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