Closed-Loop Deep Brain Stimulation to Treat Medication-Refractory Freezing of Gait in Parkinson’s Disease

Molina, Rene; Hass, Chris J.; Cernera, Stephanie; Sowalsky, Kristen; Schmitt, Abigail C.; Roper, Jaimie A.; Martínez-Ramírez, Daniel; Opri, Enrico; Hess, Christopher W.; Eisinger, Robert S.; Foote, Kelly D.; Gündüz, Ayşegül; Okun, Michael S.

doi:10.3389/fnhum.2021.633655

Cited by 27 publications

(23 citation statements)

References 53 publications

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“…Closed-loop work incorporating PPN-DBS have also begun but appear more problematic. One recent study implanted five medication-refractory FOG PD patients with two closed-loop PPN leads in addition to bilateral globus pallidus interna (GPi) leads ( Molina et al, 2021 ). However, due to surgical complications, two of these patients needed explantation of the leads.…”

Section: Surgical Approachesmentioning

confidence: 99%

Future Therapeutic Strategies for Freezing of Gait in Parkinson’s Disease

Cui

Lewis

2021

Front. Hum. Neurosci.

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Freezing of gait (FOG) is a common and challenging clinical symptom in Parkinson’s disease. In this review, we summarise the recent insights into freezing of gait and highlight the strategies that should be considered to improve future treatment. There is a need to develop individualised and on-demand therapies, through improved detection and wearable technologies. Whilst there already exist a number of pharmacological (e.g., dopaminergic and beyond dopamine), non-pharmacological (physiotherapy and cueing, cognitive training, and non-invasive brain stimulation) and surgical approaches to freezing (i.e., dual-site deep brain stimulation, closed-loop programming), an integrated collaborative approach to future research in this complex area will be necessary to systematically investigate new therapeutic avenues. A review of the literature suggests standardising how gait freezing is measured, enriching patient cohorts for preventative studies, and harnessing the power of existing data, could help lead to more effective treatments for freezing of gait and offer relief to many patients.

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Section: Surgical Approachesmentioning

confidence: 99%

Future Therapeutic Strategies for Freezing of Gait in Parkinson’s Disease

Cui

Lewis

2021

Front. Hum. Neurosci.

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“…To overcome these and other limitations of cDBS, responsive DBS (rDBS) has been introduced and relies on one or more feedback signals to modulate stimulation amplitude [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The rationale for rDBS is to provide stimulation only when necessary (i.e., when a patient is or would be experiencing symptoms).…”

Section: Introductionmentioning

confidence: 99%

“…Several rDBS studies in individuals with ET have focused on implanted electrocorticography strips [17,20,32] or local field potentials (LFP) recorded from the J o u r n a l P r e -p r o o f depth lead [22]. These studies largely depended on movement-related beta (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) desynchronization to control stimulation [17,20,32]. Additionally, studies using recordings from externalized leads in the postoperative period have demonstrated that tremor provoking movements may be decoded using both theta (4-7 Hz) and beta bands [22].…”

Section: Introductionmentioning

confidence: 99%

Wearable sensor-driven responsive deep brain stimulation for essential tremor

Cernera¹,

Alcantara²,

Opri³

et al. 2021

Brain Stimulation

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…However, the studies reported a negative relationship between increased power in this low frequency band and movement speed especially when patients were off medication, which conflicts with some of the previous literature. More recently, Molina et al (2021) reported a low frequency (1-8 Hz) power triggered closed loop PPN DBS study and showed a 40% improvement in medication-refractory freezing of gait (FoG) in three out of five PD patients with FoG. However, there is no comparison of the low frequency power triggered closed loop PPN DBS against continuous PPN DBS, so it is still difficult to establish the relationship between the low frequency oscillations in the PPN and gait.…”

Section: Introductionmentioning

confidence: 99%

Gait-Phase Modulates Alpha and Beta Oscillations in the Pedunculopontine Nucleus

Deli

Fischer

et al. 2021

J. Neurosci.

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The pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of the midbrain and pons, playing an important role in modulating posture and locomotion. Deep brain stimulation of the PPN has been proposed as an emerging treatment for patients with Parkinson's disease (PD) or multiple system atrophy (MSA) suffering gait-related atypical parkinsonian syndromes. In this study, we investigated PPN activities during gait to better understand its functional role in locomotion. Specifically, we investigated whether PPN activity is rhythmically modulated by gait cycles during locomotion. PPN local field potential (LFP) activities were recorded from PD or MSA patients suffering from gait difficulties during stepping in place or free walking. Simultaneous measurements from force plates or accelerometers were used to determine the phase within each gait cycle at each time point.Our results showed that activities in the alpha and beta frequency bands in the PPN LFPs were rhythmically modulated by the gait phase within gait cycles, with a higher modulation index when the stepping rhythm was more regular. Meanwhile, the PPN-cortical coherence was most prominent in the alpha band. Both gait-phase related modulation in the alpha/beta power and the PPN-cortical coherence in the alpha frequency band were spatially specific to the PPN and did not extend to surrounding regions. These results suggest that alternating PPN modulation may support gait control. Whether enhancing alternating PPN modulation by stimulating in an alternating fashion could positively affect gait control remains to be tested. SignificanceThe therapeutic efficacy of PPN DBS and the extent to which it can improve quality of life is still inconclusive. Understanding how PPN activity is modulated by stepping or walking may 3 offer insight into how to improve the efficacy of PPN DBS in ameliorating gait difficulties.Our study shows that PPN alpha and beta activity was modulated by the gait phase, and this was most pronounced when the stepping rhythm was regular. It remains to be tested whether enhancing alternating PPN modulation by stimulating in an alternating fashion could positively affect gait control.

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Closed-Loop Deep Brain Stimulation to Treat Medication-Refractory Freezing of Gait in Parkinson’s Disease

Cited by 27 publications

References 53 publications

Future Therapeutic Strategies for Freezing of Gait in Parkinson’s Disease

Future Therapeutic Strategies for Freezing of Gait in Parkinson’s Disease

Wearable sensor-driven responsive deep brain stimulation for essential tremor

Gait-Phase Modulates Alpha and Beta Oscillations in the Pedunculopontine Nucleus

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