Abstract Details

Title Modulation of Subthalamic Low Beta and Finely Tuned Gamma Activity with Parkinson's Therapy: Placebo Control Single-blind Study

Topic Movement Disorders

Presentation(s) S32 - Movement Disorders: Neuroimaging and Neuromodulation (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Background Beta power (13-30Hz) and finely tuned gamma (FTG, 65-90Hz) can be modulated by PD therapies. However, how DBS and medication influence STN activity at a patient specific level, compared to a placebo is still unknown.

Objective To investigate the deep brain stimulation (DBS), levodopa, and placebo on subthalamic nucleus (STN) physiology and clinical symptoms in patients with Parkinson’s disease (PD).

Design/Methods

Fourteen PD patients with bilateral STN-DBS leads, had local field potentials (LFPs) recorded 1-year after surgery, in 5-conditions: Medication ON/OFF, DBS ON/OFF, and placebo. Levodopa (1.5 times the morning dose) and saline as a placebo were administered intravenously. Symptoms were assessed with a clinical rating scale (MDS-UPDRS part III) while participants were blinded to the therapeutic condition. Five minutes of artifact-free data were selected at the end of each condition and averaged across multiple frequency bands: Alpha (8-12Hz), Low beta (LB, 13-20Hz), High beta (HB, 20-30Hz), and FTG (60-100Hz).

Results LB and HB bands were the largest in the OFF medication and were significantly reduced by DBS. Levodopa perfusion significantly reduced LB (62%) but not HB. The emergence of FTG was observed during L-dopa infusion in 46% of the recordings and was often preceded by a reduction in LB power. Adding DBS resulted in the entrainment of FTG to half the stimulation frequency (58%). Similar FTG entrainment was found in the OFF medication ON DBS (19%). The changes in both LB and FTG were correlated with the improvement rate of the symptoms, especially the akinesia and rigidity sub-scores, and were not consistently associated with dyskinesia. Interestingly, placebo administration reduced LB (36%) but did not modulate FTG.

Conclusions This study demonstrated treatment-induced changes in STN beta power and FTG in an individualized fashions. LB and FTG correlate with symptom improvement suggesting FTG and LB as biomarkers of ‘ON state’ in PD.

Authors/Disclosures
Hikaru Kamo, MD, PhD PRESENTER	Dr. Kamo has received research support from Japan Society for the Promotion of Science.
Jackson Cagle	Jackson Cagle has nothing to disclose.
Kara A. Johnson, PhD	Dr. Johnson has nothing to disclose.
Joshua Wong, MD (University of Florida College of Medicine - Neurology)	The institution of Dr. Wong has received research support from NIH.
Genko Oyama, MD, PhD, FAAN (Saitama Medical University)	Dr. Oyama has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Dr. Oyama has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Boston Scientific. Dr. Oyama has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka Pharmaceutical Co. Ltd.. Dr. Oyama has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sumitomo Dainippon Pharma Co. Ltd.. Dr. Oyama has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd.. Dr. Oyama has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharmaceutical Company LTD.. Dr. Oyama has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kyowa Hakko Kirin Co. Ltd.. Dr. Oyama has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie, Inc. The institution of Dr. Oyama has received research support from AbbVie, Inc. The institution of Dr. Oyama has received research support from GLORY LTD. The institution of Dr. Oyama has received research support from Kirin Company LTD. The institution of Dr. Oyama has received research support from Mitsubishi UFJ Lease & Finance Company LTD. The institution of Dr. Oyama has received research support from Sunwels Co., Ltd. The institution of Dr. Oyama has received research support from Ohara Pharmaceutical Co.,Ltd.. The institution of Dr. Oyama has received research support from PARKINSON Laboratories Co., Ltd..
Hirokazu Iwamuro, MD, PhD	Dr. Iwamuro has nothing to disclose.
Atsushi Umemura, MD, PhD	Prof. Umemura has nothing to disclose.
Nobutaka Hattori, MD, PhD, FANA (Juntendo University School of Medicine)	Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PARKINSON Laboratories Co., Ltd. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyowa Kirin Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TEIJIN PHARMA LIMITED.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sumitomo Dainippon Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Kyowa Kirin Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie GK. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka Holdings Co.,Ltd.. Prof. Hattori has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd. . Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sumitomo Dainippon Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis Pharma K.K.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for DAIICHI SANKYO Co., Ltd.. Prof. Hattori has received stock or an ownership interest from PARKINSON Laboratories Co., Ltd. The institution of Prof. Hattori has received research support from Japan Society for the Promotion of Science (JSPS). The institution of Prof. Hattori has received research support from Japan Agency for Medical Research and Development (AMED). The institution of Prof. Hattori has received research support from Japan Science and Technology Agency, Health Labour Sciences Research Grant. The institution of Prof. Hattori has received research support from Japan Science and Technology Agency (JST). The institution of Prof. Hattori has received research support from Kyowa Kirin Co.,Ltd.. The institution of Prof. Hattori has received research support from Medtronic, Inc.. The institution of Prof. Hattori has received research support from Boston Scientific Corporation. The institution of Prof. Hattori has received research support from TEIJIN PHARMA LIMITED.. The institution of Prof. Hattori has received research support from AbbVie GK. The institution of Prof. Hattori has received research support from FP Pharmaceutical Corporation. The institution of Prof. Hattori has received research support from Dai-Nippon Sumitomo Pharma Co.,Ltd. The institution of Prof. Hattori has received research support from Nihon Medi-physics Co.,Ltd.,. The institution of Prof. Hattori has received research support from Eisai Co.,Ltd. . The institution of Prof. Hattori has received research support from Kirin Holdings Company, Limited. The institution of Prof. Hattori has received research support from Mitsubishi UFJ Trust and Banking Corporation. The institution of Prof. Hattori has received research support from GLORY LTD.. The institution of Prof. Hattori has received research support from Nippon Life Insurance Company. The institution of Prof. Hattori has received research support from Otsuka Pharmaceutical, Co.,Ltd. The institution of Prof. Hattori has received research support from AbbVie GK,. The institution of Prof. Hattori has received research support from Meiji Seika Pharma Co., Ltd.. The institution of Prof. Hattori has received research support from Ono Pharmaceutical Co., Ltd.. The institution of Prof. Hattori has received research support from FUJIFILM Wako Pure Chemical Corporation. The institution of Prof. Hattori has received research support from Sunwels,Inc.. The institution of Prof. Hattori has received research support from OHARA Pharmaceutical Co.,Ltd.. The institution of Prof. Hattori has received research support from PARKINSON Laboratories Co., Ltd.. The institution of Prof. Hattori has received research support from Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Team Leader with RIKEN Center for Brain Science. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Program officer with AMED: Japan Agency for Medical Research and Development.
Coralie De Hemptinne, PhD	The institution of Mrs. De Hemptinne has received research support from Alpha Omega. Mrs. De Hemptinne has received personal compensation in the range of $0-$499 for serving as a grant review with Michael J Fox foundation.

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