Differential frequency modulation of neural activity in the lateral cerebellar nucleus in failed and successful grasps

Cooperrider, Jessica; Gale, John T.; Gopalakrishnan, Raghavan; Chan, Hugh H.; Wathen, Connor; Park, Hyun Joo; Baker, Kenneth B.; Shaikh, Aasef G.; Machado, André G.

doi:10.1016/j.expneurol.2015.12.007

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…Future stimulation paradigms will explore the possibility of fine-tuning and individualizing the stimulation frequency to each participant's natural frequency of cortico-cerebellar interaction. Further, we anticipate that better outcomes could be achieved if we exploit the cerebellar DN role in error prediction (Cooperrider et al, 2016) toward a closed loop paradigm of DBS that can be used along with motor training.…”

Section: Discussionmentioning

confidence: 99%

Cortico-Cerebellar Connectivity Underlying Motor Control in Chronic Poststroke Individuals

et al. 2022

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The robust, reciprocal anatomic connections between the cerebellum and contralateral sensorimotor cerebral hemisphere underscore the strong physiological interdependence between these two regions in relation to human behavior. Previous studies have shown that damage to sensorimotor cortex can result in a lasting reduction of cerebellar metabolism, the magnitude of which has been linked to poor rehabilitative outcomes. A better understanding of movement-related cerebellar physiology as well as cortico-cerebellar coherence (CCC) in the chronic, poststroke state may be key to developing novel neuromodulatory techniques that promote upper limb motor rehabilitation. As a part of the first in-human phase I trial investigating the effects of deep brain stimulation of the cerebellar dentate nucleus (DN) on chronic poststroke motor rehabilitation, we collected invasive recordings from DN and scalp EEG in participants (both sexes) with middle cerebral artery stroke during a visuo-motor tracking task. We investigated the excitability of ipsilesional cortex, DN, and their interaction as a function of motor impairment and performance. Our results indicate the following: (1) event-related oscillations in the ipsilesional cortex and DN were significantly correlated at movement onset in the low beta band, with moderately and severely impaired participants showing desynchronization and synchronization, respectively; and (2) significant CCC was observed during the isometric hold period in the low beta band, which was critical for maintaining task accuracy. Our findings support a strong coupling between ipsilesional cortex and DN in the low beta band during motor control across all impairment levels, which encourages the exploitation of the cerebello-thalamo-cortical pathway as a neuromodulation target to promote rehabilitation.

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Section: Discussionmentioning

confidence: 99%

Cortico-Cerebellar Connectivity Underlying Motor Control in Chronic Poststroke Individuals

et al. 2022

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“…To this end, our group has recently shown increased beta- band activity in the LCN prior to the initiation of unsuccessful reaching motions compared to successful attempts, a finding that may allow for the design and development of local field potential-informed closed-loop stimulation triggering. 12 Ongoing work in our laboratory is aimed at developing such a closed-loop system based on real-time detection of animal behavior.…”

Section: Preclinical Studiesmentioning

confidence: 99%

Deep brain stimulation of the cerebellum for poststroke motor rehabilitation: from laboratory to clinical trial

Wathen

Frizon

Maiti

et al. 2018

Neurosurgical Focus

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Ischemic stroke is a leading cause of disability worldwide, with profound economic costs. Poststroke motor impairment is the most commonly encountered deficit resulting in significant disability and is the primary driver of stroke-associated healthcare expenditures. Although many patients derive some degree of benefit from physical rehabilitation, a significant proportion continue to suffer from persistent motor impairment. Noninvasive brain stimulation, vagal nerve stimulation, epidural cortical stimulation, and deep brain stimulation (DBS) have all been studied as potential modalities to improve upon the benefits derived from physical therapy alone. These neuromodulatory therapies aim primarily to augment neuroplasticity and drive functional reorganization of the surviving perilesional cortex.The authors have proposed a novel and emerging therapeutic approach based on cerebellar DBS targeted at the dentate nucleus. Their rationale is based on the extensive reciprocal connectivity between the dentate nucleus and wide swaths of cerebral cortex via the dentatothalamocortical and corticopontocerebellar tracts, as well as the known limitations to motor rehabilitation imposed by crossed cerebellar diaschisis. Preclinical studies in rodent models of ischemic stroke have shown that cerebellar DBS promotes functional recovery in a frequency-dependent manner, with the most substantial benefits of the therapy noted at 30-Hz stimulation. The improvements in motor function are paralleled by increased expression of markers of synaptic plasticity, synaptogenesis, and neurogenesis in the perilesional cortex. Given the findings of preclinical studies, a first-in-human trial, Electrical Stimulation of the Dentate Nucleus Area (EDEN) for Improvement of Upper Extremity Hemiparesis Due to Ischemic Stroke: A Safety and Feasibility Study, commenced in 2016. Although the existing preclinical evidence is promising, the results of this Phase I trial and subsequent clinical trials will be necessary to determine the future applicability of this therapy.

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“…In vivo characterization of DTC physiology holds significance for design and refinement of dentate nucleus DBS for post-stroke motor recovery and offers an important biomarker of response to our own efforts to translate novel DBS treatments targeting the cerebellum. 4,17,24,25…”

Section: Introductionmentioning

confidence: 99%

Paired DBS and TMS Reveals Dentato-Cortical Facilitation Underlying Upper Extremity Movement in Chronic Stroke Survivors

Li,

Baker,

O’Laughlin

et al. 2023

Neurorehabil Neural Repair

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Background Cerebellum shares robust di-synaptic dentato-thalamo-cortical (DTC) connections with the contralateral motor cortex. Preclinical studies have shown that DTC are excitatory in nature. Structural integrity of DTC is associated with better upper extremity (UE) motor function in people with stroke, indicating DTC are important for cerebellar influences on movement. However, there is a lack of understanding of physiologic influence of DTC in humans, largely due to difficulty in accessing the dentate nucleus. Objective Characterize DTC physiology using dentate nucleus deep brain stimulation (DBS) combined with transcranial magnetic stimulation (TMS) in stroke. Methods Nine chronic stroke survivors with moderate-to-severe UE impairment (Fugl-Meyer 13-38) underwent a paired DBS–TMS experiment before receiving experimental dentate nucleus DBS in our first-in-human phase I trial (Baker et al., 2023, Nature Medicine). Conditioning DBS pulses were given to dentate nucleus 1 to 10 ms prior to supra-threshold TMS pulses given to ipsilesional motor cortex. Effects were assessed on motor evoked potentials (MEPs). Size of DBS-conditioned MEPs was expressed relative to TMS MEPs, where values >1 indicate facilitation. Results Dentate nucleus DBS led to facilitation of MEPs at short-latency intervals (3.5 and 5 ms, P = .049 and .021, respectively), a phenomenon we have termed dentato-cortical facilitation (DCF). Higher DCF was observed among patients with more severe UE impairment. Diffusion tensor imaging revealed microstructure of thalamo-cortical portion of DTC was related to higher corticomotor excitability. Conclusions Our in vivo investigation reveals for the first time in humans the intrinsic excitatory properties of DTC, which can serve as a novel therapeutic target for post-stroke motor recovery.

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Differential frequency modulation of neural activity in the lateral cerebellar nucleus in failed and successful grasps

Cited by 6 publications

References 37 publications

Cortico-Cerebellar Connectivity Underlying Motor Control in Chronic Poststroke Individuals

Cortico-Cerebellar Connectivity Underlying Motor Control in Chronic Poststroke Individuals

Deep brain stimulation of the cerebellum for poststroke motor rehabilitation: from laboratory to clinical trial

Paired DBS and TMS Reveals Dentato-Cortical Facilitation Underlying Upper Extremity Movement in Chronic Stroke Survivors

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