Bilateral Closed Loop Deep Brain Stimulation for Freezing of Gait using Neural and Kinematic Feedback

利用神经和运动学反馈进行双边闭环深部脑刺激以冻结步态

• 批准号: 10218278
• 负责人: Helen Bronte-Stewart
• 金额: $ 120.42万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218278
• 关键词: Adverse effects; Affect; Age; Algorithms; Behavior Control; Behavioral; Bilateral; Bluetooth; Bradykinesia; Brain; Cessation of life; Clinical Research; Complication; Data; Deep Brain Stimulation; Development; Device or Instrument Development; Devices; Disease; Dose; Emerging Technologies; Environment; Family; Feedback; Freezing; Frequencies; Future; Gait; Gap Junctions; Glues; Home; Home environment; Impairment; Implant; Incidence; Independent Living; Industry Collaboration; Injury; Lead; Leg; Lewy Body Dementia; Locomotion; Measurement; Measures; Motor; Movement Disorder Society Unified Parkinson' s Disease Rating Scale; National Institute of Neurological Disorders and Stroke; Neurodegenerative Disorders; Outcome; Outcome Measure; Parkinson Disease; Patients; Periodicity; Pharmaceutical Preparations; Policies; Population; Progressive Supranuclear Palsy; Research; Research Priority; Safety; Signal Transduction; Structure of subthalamic nucleus; System; Technology; Testing; Time; Translating; Tremor; Walking; arm; base; bench to bedside; cohort; design; disability; effective therapy; experience; experimental study; fall injury; falls; feasibility testing; foot; home test; improved; kinematics; motor disorder; motor symptom; nervous system disorder; neuroregulation; next generation; novel; partial response; participant safety; patient safety; prevent; primary outcome; relating to nervous system; response; safety and feasibility; safety testing; secondary outcome; sensor; side effect; symposium; wearable sensor technology

Gait impairment and Freezing of gait (FOG), lead to falls, injury (even death), loss of independent living, and are common in neurodegenerative diseases such as Parkinson’s Disease (PD), affecting over 7 million people worldwide. The incidence of neurodegenerative diseases increases with age and as the population lives longer, the societal consequences of FOG, will be very significant. Gait impairment and FOG have a partial response to medication and subthalamic nucleus (STN) open loop deep brain stimulation (olDBS), which cannot adjust therapy in response to underlying brain signals or motor symptoms such as FOG. One reason is that FOG may respond to different parameters of DBS, such as lower frequency, than that needed for tremor and most patients do not tolerate 60 Hz DBS for long periods of time. Emerging technology using sensing neurostimulators and Bluetooth enabled wearable sensors has allowed research into closed loop or adaptive (a)DBS using neural or behavioral control variables. FOG is episodic and usually occurs in predictable environments, so it is well suited for ‘on demand’ aDBS. ADBS, responding to markers of gait impairment and intermittent FOG, with changes in DBS intensity or frequency, could then prevent FOG, falls and injury, while still treating other motor signs of PD. From over four years of research and regulatory experience in an academic-industry collaboration with Medtronic, we have provided design inputs for the next generation aDBS devices, and have determined that aDBS for tremor and bradykinesia is safe and tolerable in the largest freely-moving PD cohort implanted with a Medtronic investigative neurostimulation/sensing system (Activa® PC+S-Nexus D/D3/E). We have discovered neural and behavioral markers of gait impairment and FOG using synchronized neural and kinematic recordings during gait tasks that elicit FOG. Our research findings and the technological advances embedded in the Medtronic Summit® RC+S-system now enable the next step: the first clinical studies of lateralized, independent, bilateral STN aDBS control algorithms for FOG in PD, driven by subject-specific neural (Aim 1) or behavioral (Aim 2) control variables, and in response to medication (Aim 3). The project will translate stepwise in a ‘bench to bedside’ manner, testing aDBS during the stepping in place (SIP) task, where the subject is in a harness and steps in place on dual force-plates. Then aDBS will be tested during the forward walking Turning and Barrier Course, which mimics environments known to trigger FOG in the real world, and then how aDBS responds to subject-specific doses of medication, while freely moving. The outcome of these experiments will provide critical next-steps for safety and feasibility of testing aDBS for gait impairment and FOG in the subject’s home environment, and on their normal medication. Patient safety, tolerability, adverse effects, gait parameters, and the number and duration of freezing episodes (FEs), during no DBS, olDBS, aDBS and a control, intermittent (i)olDBS will provide inputs for future devices and novel algorithms applicable to NaDBS or KaDBS for gait impairment and FOG in other neurological diseases.

步态障碍和步态冻结（FOG）会导致跌倒、受伤（甚至死亡）、丧失独立生活能力