Musa Ozturk1, Aviva Abosch2, David Francis3, Jianping Wu4, Joohi Jimenez-Shahed5, Nuri F Ince1. 1. Department of Biomedical Engineering, University of Houston, Houston, Texas, USA. 2. Department of Neurosurgery, University of Colorado, Aurora, Colorado, USA. 3. Department of Psychology, University of Houston, Houston, Texas, USA. 4. Restorative Therapies Group Implantables, Research and Core Technology, Medtronic, Minneapolis, Minnesota, USA. 5. Department of Neurology, Baylor College of Medicine Houston, Texas, USA.
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.
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.
Authors: Luke A Johnson; Joshua E Aman; Ying Yu; David Escobar Sanabria; Jing Wang; Meghan Hill; Rajiv Dharnipragada; Remi Patriat; Mark Fiecas; Laura Li; Lauren E Schrock; Scott E Cooper; Matthew D Johnson; Michael C Park; Noam Harel; Jerrold L Vitek Journal: Mov Disord Date: 2021-04-13 Impact factor: 9.698
Authors: Joshua K Wong; Günther Deuschl; Robin Wolke; Hagai Bergman; Muthuraman Muthuraman; Sergiu Groppa; Sameer A Sheth; Helen M Bronte-Stewart; Kevin B Wilkins; Matthew N Petrucci; Emilia Lambert; Yasmine Kehnemouyi; Philip A Starr; Simon Little; Juan Anso; Ro'ee Gilron; Lawrence Poree; Giridhar P Kalamangalam; Gregory A Worrell; Kai J Miller; Nicholas D Schiff; Christopher R Butson; Jaimie M Henderson; Jack W Judy; Adolfo Ramirez-Zamora; Kelly D Foote; Peter A Silburn; Luming Li; Genko Oyama; Hikaru Kamo; Satoko Sekimoto; Nobutaka Hattori; James J Giordano; Diane DiEuliis; John R Shook; Darin D Doughtery; Alik S Widge; Helen S Mayberg; Jungho Cha; Kisueng Choi; Stephen Heisig; Mosadolu Obatusin; Enrico Opri; Scott B Kaufman; Prasad Shirvalkar; Christopher J Rozell; Sankaraleengam Alagapan; Robert S Raike; Hemant Bokil; David Green; Michael S Okun Journal: Front Hum Neurosci Date: 2022-03-04 Impact factor: 3.473