Deep Brain Stimulation of the Interposed Nucleus Reverses Motor Deficits and Stimulates Production of Anti-inflammatory Cytokines in Ataxia Mice

Kumar, Gajendra; Asthana, Pallavi; Yung, Wing-Ho; Kwan, Kin Ming; Tin, Chung; Eddie, Chi Him

doi:10.1007/s12035-022-02872-w

Cited by 8 publications

(26 citation statements)

References 75 publications

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“…The ataxia (DKO) mice exhibit disrupted cerebellar circuitry leading to nonprogressive cerebellar ataxia (no degeneration of PCs) and severe motor deficits. 28,29 Our results confirm the superiority of FPGA-based closed-loop DCN-DBS for alleviating cerebellar ataxia. This evidence supports the effectiveness of closed-loop DCN-DBS not only for cerebellar ataxia, but also for other movement disorders.…”

Section: Introductionsupporting

confidence: 70%

“…To address these issues, use of a FPGA-based platform in BCI devices and closedloop controls have been reported. [46][47][48] Electromyography recording allows detection of functional neuromuscular synapses at target muscles and is widely used to quantify motor function recovery 29,31,34,[50][51][52] and motor deficits in movement disorders. For instance, surface EMG (sEMG) from symptomatic extremities can be used to predict the onset of tremor in essential tremor patient 53 with an accuracy of over 80% in PD and essential tremor patients.…”

Section: Discussionmentioning

confidence: 99%

“…Mice were anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg) for customized electrode implantation into the GCM as described previously. 29,[31][32][33] Briefly, a 1-cm incision on the head was made and the electrode connector was affixed to the skull with dental cement. The wire between the electrode connector and GCM was inserted subcutaneously from the dorsal neck to the leg.…”

Section: Gcm Emg Recording In Freely Moving Micementioning

confidence: 99%

“…Spontaneous GCM EMG recording was performed using Apollo the skull surface, and affixed to the skull with dental cement. 29,36 The reference electrode was placed over the frontal bone. Animal health status was daily monitored for 1 week post-surgery to en-…”

Section: Gcm Emg Recording In Freely Moving Micementioning

confidence: 99%

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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

Kumar,

Zhou,

Wang

et al. 2024

CNS Neurosci Ther

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AimsThe 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.MethodsWe 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.ResultsClosed‐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.ConclusionOur real‐time FPGA‐based DCN‐DBS system could be a potential clinical strategy for alleviating cerebellar ataxia and other movement disorders.

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Section: Introductionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Gcm Emg Recording In Freely Moving Micementioning

confidence: 99%

Section: Gcm Emg Recording In Freely Moving Micementioning

confidence: 99%

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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

Kumar,

Zhou,

Wang

et al. 2024

CNS Neurosci Ther

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“…Effects of cerebellar DBS have been examined in various animal models of degenerative ataxia using different targets [ 164 , 165 , 166 ]. Many types of degenerative ataxia are characterized by loss of Purkinje cells, which leads to an altered output to the deep cerebellar nuclei [ 167 ].…”

Section: Cerebellar Dbs In Hereditary Ataxiasmentioning

confidence: 99%

The Therapeutic Potential of Non-Invasive and Invasive Cerebellar Stimulation Techniques in Hereditary Ataxias

Benussi

Batsikadze

França

et al. 2023

Cells

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The degenerative ataxias comprise a heterogeneous group of inherited and acquired disorders that are characterized by a progressive cerebellar syndrome, frequently in combination with one or more extracerebellar signs. Specific disease-modifying interventions are currently not available for many of these rare conditions, which underscores the necessity of finding effective symptomatic therapies. During the past five to ten years, an increasing number of randomized controlled trials have been conducted examining the potential of different non-invasive brain stimulation techniques to induce symptomatic improvement. In addition, a few smaller studies have explored deep brain stimulation (DBS) of the dentate nucleus as an invasive means to directly modulate cerebellar output, thereby aiming to alleviate ataxia severity. In this paper, we comprehensively review the clinical and neurophysiological effects of transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and dentate nucleus DBS in patients with hereditary ataxias, as well as the presumed underlying mechanisms at the cellular and network level and perspectives for future research.

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Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke

Au,

Wu,

Kumar

et al. 2024

Brain, Behavior, and Immunity

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Deep Brain Stimulation of the Interposed Nucleus Reverses Motor Deficits and Stimulates Production of Anti-inflammatory Cytokines in Ataxia Mice

Cited by 8 publications

References 75 publications

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

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

The Therapeutic Potential of Non-Invasive and Invasive Cerebellar Stimulation Techniques in Hereditary Ataxias

Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke

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