Distinct subthalamic coupling in the ON state describes motor performance in Parkinson's disease

Musa Ozturk, Aviva Abosch, David Francis, Jianping Wu, Joohi Jimenez-Shahed, Nuri F. Ince

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Objective: Cross-frequency coupling has been reported in the STN of patients with PD, but its significance and functional role are still not well understood. This study investigates pharmacological modulations of subthalamic oscillations and their nonlinear cross-frequency interactions across three consecutive cycles over unique 24-hour-long recordings. Background: Identifying neurobiomarkers for PD can drive the development of novel personalized treatments by providing objective assessment of impairment. In particular, distinct frequency bands in LFP recordings and their interaction with one another have been shown to modulate with dopaminergic medication and thus, proposed as such biomarkers. Methods: We recorded local field potentials 3 weeks postoperatively from externalized leads in 9 patients and correlated the neural patterns with improvements in motor signs over three medication intake cycles. We used two modalities to assess symptoms in the unmedicated OFF and the l-dopa–induced motor ON state: a subsection of the UPDRS and a keyboard tapping score measuring bradykinesia. Results: In the OFF state, the amplitude of high-frequency oscillations in the 200- to 300-Hz range was coupled with the phase of low-beta (13–22 Hz) in all patients. After transition to the ON state, three distinct coupling patterns were observed among subjects. Among these, patients showing ON coupling between high-beta (22–30 Hz) and high-frequency oscillations in the 300- to 400-Hz range had significantly greater improvement in bradykinesia, according to the keyboard scores. Conclusion: Observing diminished coupling in the ON state, previous studies have hypothesized that the sole existence of coupling in STN has an “impeding” effect on normal processes, and thus it was considered to be pathological. In contrast, our observation of ON state coupling at distinct frequencies associated with the improvements in motor features suggest that the underlying mechanism of coupling might have impeding or enhancing effects depending on the coupled frequencies.

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalMovement Disorders
Volume35
Issue number1
DOIs
StatePublished - 1 Jan 2020
Externally publishedYes

Keywords

  • Parkinson's disease
  • cross-frequency coupling
  • levodopa
  • local field potentials
  • subthalamic nucleus

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