Journal Article

Real‐time field‐programmable gate array‐based closed‐loop deep brain stimulation platform targeting cerebellar circuitry rescues motor deficits in a mouse model of cerebellar ataxia

Wang, Zhihua, Kumar, Gajendra, Kwan, Kin Ming, Ma, Chi Him Eddie, Tin, Chung, Zhou, Zhanhong

2024

Overview

Aims The open‐loop nature of conventional deep brain stimulation (DBS) produces continuous and excessive stimulation to patients which contributes largely to increased prevalence of adverse side effects. Cerebellar ataxia is characterized by abnormal Purkinje cells (PCs) dendritic arborization, loss of PCs and motor coordination, and muscle weakness with no effective treatment. We aim to develop a real‐time field‐programmable gate array (FPGA) prototype targeting the deep cerebellar nuclei (DCN) to close the loop for ataxia using conditional double knockout mice with deletion of PC‐specific LIM homeobox (Lhx)1 and Lhx5, resulting in abnormal dendritic arborization and motor deficits. Methods We implanted multielectrode array in the DCN and muscles of ataxia mice. The beneficial effect of open‐loop DCN‐DBS or closed‐loop DCN‐DBS was compared by motor behavioral assessments, electromyography (EMG), and neural activities (neurospike and electroencephalogram) in freely moving mice. FPGA board, which performed complex real‐time computation, was used for closed‐loop DCN‐DBS system. Results Closed‐loop DCN‐DBS was triggered only when symptomatic muscle EMG was detected in a real‐time manner, which restored motor activities, electroencephalogram activities and neurospike properties completely in ataxia mice. Closed‐loop DCN‐DBS was more effective than an open‐loop paradigm as it reduced the frequency of DBS. Conclusion Our real‐time FPGA‐based DCN‐DBS system could be a potential clinical strategy for alleviating cerebellar ataxia and other movement disorders. Conventional open‐loop DBS provides continuous stimulation, regardless of changes in physiologic state. Our FPGA‐based closed‐loop DBS system is triggered only when symptomatic muscle EEG is detected in a real‐time manner, which reduced the frequency and time of DBS, preventing over neural stimulation that shortens the battery life of stimulator. The real‐time FPGA‐based closed‐loop DBS system demonstrates a proof‐of‐concept, supporting its potential clinical application in integrating the new generation of implantable pulse generator and external wireless wearable EEG devices for movement disorder.

• Publisher: John Wiley & Sons, Inc
• Subject: Animals / Ataxia / Biomarkers / Cerebellar ataxia / Cerebellar Ataxia - genetics / Cerebellar Ataxia - therapy / Cerebellar Nuclei - physiology / Cerebellum / Coordination / Deep brain stimulation / Deep Brain Stimulation - methods / Dendritic branching / EEG / electroencephalography / Electromyography / Experiments / Field programmable gate arrays / field‐programmable gate array / Homeobox / Humans / Mice / Motor ability / Movement Disorders / Muscles / Parkinson's disease / Purkinje cells / Purkinje Cells - physiology / Software / Transistors / Universal Serial Bus