A recent study published in eNeuro suggests that a non-invasive brain wave test – an EEG – could help diagnose or measure Parkinson’s disease. Nicole Swann, PhD, and colleagues at the University of Oregon analyzed the EEGs of 15 people with Parkinson’s and 16 people without it. They found that the brain waves of people with Parkinson’s had different angles and sharpness, and that their brain waves differed when they were on and off medication.
To understand these results, we spoke with Lenora Higginbotham, MD, Senior Associate in the Department of Neurology at Emory in Atlanta, Georgia, Edmond J. Safra Fellowship Class of 2018, who also studies EEG in Parkinson’s.
The Michael J. Fox Foundation (MJFF): What do the results of this study mean?
Lenora Higginbotham (LH): In people with Parkinson’s, there is abnormal brain cell activity. The electrical activity, which cells use to talk to each other, is too coordinated. We call this synchrony. We can study synchrony with EEG, and there are different ways to measure it – the sharpness and steepness of brain waves, as well as “phase amplitude coupling” (how coordinated the brain waves are). It is unclear what is the best or most reliable way to measure synchrony.
Looking at the brain waves of a group of patients, as Dr. Swann and her colleagues did, can be potentially helpful because we don’t have a biomarker (an objective measure) to distinguish Parkinson’s disease from other disorders or to see whether therapy is actually working. We have to rely on our examination and a patient’s report of symptoms and medication benefit (or lack thereof). These types of EEG measurements could be directly applied to deep brain stimulation (DBS) adjustments as well. DBS programming is complex. Doctors manually adjust settings based on a patient’s symptoms and examination, but if EEG measures could be incorporated into these systems (if implanted electrodes could record and recognize brain wave activity), these systems could program themselves. This is known as “adaptive” or “smart” DBS, which currently is being tested in clinical trials.
MJFF: What is an EEG?
LH: EEG stands for electroencephalogram. It is a non-invasive technique in which electrodes are placed with a paste or cap onto the scalp to measure brain waves. EEG is normally used to detect seizures or to see if people are prone to seizures. By looking at brain waves, we also can tell if a person is awake or asleep, if they’re moving and if the eyes are blinking. When studying Parkinson’s, we use standard EEGs, but we perform a more detailed data analysis to look for more subtle abnormalities.
MJFF: Tell us about your research with EEG and Parkinson’s.
LH: I’ve been working with my mentor, Dr. Svjetlana Miocinovic, to look at EEG measures of synchrony to see if we can apply these as biomarkers in Parkinson’s – as diagnostic markers, to monitor treatment or for adaptive DBS. What I was doing during my Edmond J. Safra Fellowship in Movement Disorders and what I continue to do now is look at EEGs in Parkinson’s through two different angles. One is comparing EEGs in people with atypical parkinsonism (conditions that look like Parkinson’s) to those in people with Parkinson’s disease to see if EEG could be a diagnostic tool. Even when people see a specialist like me, these diseases can be hard to distinguish, and I want to see if EEG can help with diagnosis. I’m also looking at EEG brain waves during sleep in people with Parkinson’s because this has rarely been done. If we want to put these measurements in adaptive DBS, we should know what brain waves look like when people are awake and asleep. Both studies are still in progress and we are analyzing the data. In the sleep study, we found that synchrony seems to go up during sleep, which is interesting. You would think this abnormal activity would go down, because movement disorders, such as tremor, rigidity and stiffness, disappear in sleep. We also see challenges with EEG – it can be hard to replicate and interpret. EEG depends on an individual person, and results are susceptible to the way you analyze data or techniques you use. In the sleep study, for example, the data seems to be cleaner and is easier to interpret – maybe that’s because there is less movement.
MJFF: How close are we to a Parkinson’s biomarker?
LH: We are getting there. There are many potential biomarkers – protein levels in the blood, brain imaging markers, EEG and possibly others. Several are in the research phase. We are seeing how useful they are. Alzheimer’s is ahead in that you can measure amyloid and tau proteins in the spinal fluid; Parkinson’s is working toward something like that and we have promising leads. A potential marker like EEG has a unique position in Parkinson’s because of DBS and the underlying biology of disease. We know what neurons are communicating with each other, we know the loop that controls disease and we know that modulating that loop (such as with DBS) can control symptoms. This, and the fact that EEG is non-invasive, makes it useful and promising as a biomarker. I do think EEG will play a role as a biomarker, perhaps as part of a larger effort. Parkinson’s is so complex that we may need to look at a combination of measures, such as proteins, imaging and EEG, to make a diagnosis and determine where one particular person is headed with the disease.
MJFF: You’re a clinician and a researcher. What does that mean?
LH: I do a combination of clinic – seeing movement disorder patients – and research. Right now, I do mostly research, about 80 percent of the time. My research looks at biomarkers in Parkinson’s – not only EEGs but also proteomics, which is the study of proteins. We’re trying to develop panels of proteins that could predict who might develop cognitive (thinking and memory) decline. We’re studying people with Parkinson’s, people with Parkinson’s and dementia, and people who have dementia with Lewy bodies to see what proteins make them different and may be associated with more aggressive cognitive decline. In the research setting, I work with biochemists and lab scientists, so my ties to the clinic are helpful to bring the patient experience to them – I can help them understand what people with Parkinson’s look like, or that not all of them have tremor, for example. In the clinic, I can help patients understand and get involved in research opportunities while I help them manage their disease.