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

© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:30

Enthalten in:

CNS neuroscience & therapeutics - 30(2024), 3 vom: 15. März, Seite e14638

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Cerebellar ataxia
Cerebellum
Deep brain stimulation
Electroencephalography
Electromyography
Field-programmable gate array
Journal Article
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 18.03.2024

Date Revised 18.04.2024

published: Print

Citation Status MEDLINE

doi:

10.1111/cns.14638

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369781341