Brain-Wave Patterns Distinguish Parkinson’s Subtypes

Deep-brain stimulation can improve symptoms of Parkinson’s disease, but it does not work for all patients. Now, a paper in the August 21 Proceedings of the National Academy of Sciences suggests that characteristic brain waves set subtypes of PD apart, and might help clinicians improve DBS. Scientists led by Nuri Ince, University of Houston, found different oscillation patterns in the subthalamic nucleus (STN) in people with tremor-dominant PD, compared with patients with mostly postural instability and gait difficulty. “We think we can use these features to personalize DBS treatments,” said first author Ilknur Telkes. “In doing so we might increase the efficacy of DBS, especially in those who receive suboptimal benefit.”

Warren Grill, Duke University, Durham, North Carolina, agreed. “It was not known before that oscillatory patterns differ across symptom profiles or types of PD,” he told Alzforum. “I was really excited by the finding because I think it has important implications for future developments in DBS.” Grill was not involved in the study.  

Telkes and colleagues analyzed recordings taken from microelectrodes used to guide DBS surgery. During the procedure, surgeons record activity at different depths of the brain to find an optimal place to implant electrodes. Telkes analyzed recordings taken from 24 patients, trying to find tell-tale differences.

Patients fell into two main groups based on their oscillation patterns. One group of 13 was made up of tremor-dominant (TD) patients, while the other 11 patients had primarily postural instability and gait difficulty (PIGD). In the TD patients, microelectrodes picked up a high-frequency oscillation of 200 to 260 Hz in the top 2 mm of the STN. The amplitude of that oscillation coupled strongly with the phase of the beta oscillation, which is typically in the 13–30 Hz range. Both TD and PIGD groups had faster high-frequency oscillations of 260–400 Hz at greater depths, between 2 mm and 5 mm, but these oscillations were more strongly coupled to the beta oscillations in the PIGD group (see image below).

Strong Coupling, Different Areas.

In the upper subthalamic nucleus (top panels), high-frequency oscillations coupled with beta oscillations (color bar shows strength) in TD patients (left) but not in PIGD patients (right). The opposite pattern emerged in the lower STN. [Courtesy of Telkes et al., 2018.]

Studies of other populations will be needed to confirm these findings, Telkes said. It’s not clear yet whether these data will be helpful for DBS, but they suggest that taking a patient’s symptom profile into account could help surgeons place DBS electrodes and optimally stimulate the brain, said Grill. Perhaps placing electrodes higher up in the STN in TD-PD might disrupt high frequency/beta coupling there, while placing electrodes deeper in PIGD patients would be better. Previous studies found that when levodopa and DBS disrupted coupling in the subthalamic nucleus, PD symptoms improved (López-Azcárate et al., 2010). 

However, Maya Katz, University of California, San Francisco, cautioned that people with PD can fluctuate from year to year between TD and PIGD subtypes (Simuni et al., 2016). “It would be very difficult to target DBS on a biomarker that is changing as the disease progresses,” she told Alzforum. Finding the abnormal oscillations to target in DBS is important, she said, but she believes researchers should aim for something more stable.—Gwyneth Dickey Zakaib

Comments

  1. While many papers in the last 15 years have examined field potentials in the subthalamic nucleus and their relationship to parkinsonian symptoms, the vast majority have been done using recordings from large “macrolectrodes” (deep-brain stimulation lead contacts) with spatial resolution of approximately 2 mm. This paper exploits the greater spatial resolution of recording from smaller, temporary electrodes that are used intraoperatively, to map in detail the spatial distribution of specific physiological features.

    The paper clearly demonstrates regional differences in high-frequency activity (200-400 Hz) that distinguish the two predominant parkinsonian subtypes, tremor dominant versus postural instability/gait disorder. This is the first paper to clearly demonstrate an electrophysiologic marker that distinguishes these forms.

    The biophysical origins of these differences in high-frequency activity remain unclear but will help to refine circuit models of the motor network in PD.

    View all comments by Philip Starr

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References

Paper Citations

  1. López-Azcárate J, Tainta M, Rodríguez-Oroz MC, Valencia M, González R, Guridi J, Iriarte J, Obeso JA, Artieda J, Alegre M. Coupling between beta and high-frequency activity in the human subthalamic nucleus may be a pathophysiological mechanism in Parkinson's disease. J Neurosci. 2010 May 12;30(19):6667-77. PubMed.
  2. Simuni T, Caspell-Garcia C, Coffey C, Lasch S, Tanner C, Marek K, PPMI Investigators. How stable are Parkinson's disease subtypes in de novo patients: Analysis of the PPMI cohort?. Parkinsonism Relat Disord. 2016 Jul;28:62-7. Epub 2016 Apr 23 PubMed.

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