Personalized chronic adaptive deep brain stimulation outperforms conventional stimulation in Parkinson’s disease

Oehrn, Carina R.; Cernera, Stephanie; Hammer, Lauren H; Shcherbakova, Maria; Yao, Jingjing; Hahn, Andreas; Wang, Sarah; Ostrem, Jill L.; Little, Simon; Starr, Philip A.

doi:10.1101/2023.08.03.23293450

Cited by 16 publications

(18 citation statements)

References 65 publications

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“…In this context, entrained gamma is proposed as a feedback biomarker for adaptive DBS. 41 Our results call for a more differentiated analysis of the entrained signal. Interestingly, dyskinesia only occurred in those patients (three out of eight) that presented spontaneous FTG under dopaminergic medication before stimulation was switched on.…”

Section: Discussionmentioning

confidence: 76%

“…DBS-induced gamma entrainment has been recently introduced as a feedback signal for closed-loop DBS. 41 Here, stimulation-entrained gamma is used to adjust DBS parameter, specifically to control DBS amplitude reduction because this biomarker has been related to dyskinesia. Entrained gamma on one hand is a potential robust closed-loop DBS input signal as it has an entirely predictable frequency and large peak amplitude, which can be also used in chronic devices with limited spectral recording bandwidth.…”

Section: Discussionmentioning

confidence: 99%

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DBS-induced gamma entrainment as a new biomarker for motor improvement with neuromodulation

Mathiopoulou,

Habets,

Feldmann

et al. 2024

Preprint

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Finely tuned gamma oscillations have been recorded from the subthalamic nucleus and cortex in Parkinson's disease patients undergoing deep brain stimulation and are often associated with dyskinesia. More recently, it was shown that deep brain stimulation entrains finely tuned gamma to 1/2 of the stimulation frequency; however, the functional role of this signal is not yet fully understood. We recorded local field potentials from the subthalamic nucleus in 19 chronically implanted Parkinson's disease patients under effective dopaminergic medication and during deep brain stimulation with increasing stimulation amplitude, while they were at rest and during repetitive hand movements. We analyzed the effect of stimulation intensity on gamma band 1:2 entrainment and compared the entrained signal during rest and during repetitive movement. Spontaneous finely tuned gamma was present in eight out of 19 patients (peak frequency μ = 78.4 ±4.3 Hz). High-frequency deep brain stimulation induced 1:2 gamma entrainment in 15 out of 19 patients. Entrainment occurred at a mean stimulation amplitude of 2.2 ±0.75 mA and disappeared or decreased in power during higher stimulation amplitude in three patients. In patients with spontaneous finely tuned gamma, increasing the stimulation amplitude induced a progressive frequency shift of spontaneous finely tuned gamma until it locked to 1:2 entrainment. Only five out of 15 patients with entrained gamma activity showed dyskinesia during stimulation. Further, there was a significant increase in the power of 1:2 entrained gamma activity during movement in comparison to rest. Finally, patients with entrained gamma activity had faster movements as compared to those without gamma entrainment. These findings argue for a functional relevance of the stimulation-induced 1:2 gamma entrainment in Parkinson's disease patients as a prokinetic activity that, however, is not necessarily promoting dyskinesia. Previously published electrophysiological models of entrainment fit well to our results and support our findings that stimulation-induced entrainment can be a promising real-life biomarker for closed-loop deep brain stimulation.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

DBS-induced gamma entrainment as a new biomarker for motor improvement with neuromodulation

Mathiopoulou,

Habets,

Feldmann

et al. 2024

Preprint

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“…Beta frequency oscillatory activity within the cortico-basal ganglia circuit has proven to be a robust biomarker of motoric impairments – particularly bradykinesia and rigidity - in PD 4,7,39,40 . Moreover, aDBS approaches which involve the delivery of STN stimulation only after the detection of beta bursts are more effective in terms of achieving motor benefit and limiting stimulation related side effects, than conventional continuous DBS 15–17,41 . Although aDBS been shown to be effective, a key drawback of beta amplitude triggered approaches is that they cannot prevent the onset of pathological beta bursts, but rather respond with some fixed delay following burst onset.…”

Section: Discussionmentioning

confidence: 99%

Prediction of pathological subthalamic nucleus beta burst occurrence in Parkinson’s disease

Abdi-Sargezeh,

Shirani,

Sharma

et al. 2024

Preprint

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The cortico-basal ganglia network in Parkinson's disease (PD) is characterised by the emergence of transient episodes of exaggerated beta frequency oscillatory synchrony known as bursts. Although beta bursts of prolonged duration and amplitude are well recognised to have a detrimental effect on motor function in PD, the neurophysiological mechanisms leading to burst initiation remain poorly understood. Related to this is the question of whether there exist features of basal ganglia activity which can reliably predict the onset of beta bursts. Current state-of-the-art adaptive Deep Brain Stimulation (aDBS) algorithms for PD involve the reactive delivery of stimulation following burst detection and are unable to stimulate proactively so as to prevent burst onset. The discovery of a predictive biomarker would allow for such proactive stimulation, thereby offering further potential for improvements in both the efficacy and side effect profile of aDBS. Here we use deep neural networks to address the hypothesis that beta bursts can be predicted from invasive subthalamic nucleus (STN) recordings in PD patients. We developed a neural network which was able to predict bursts 31.6ms prior to their onset, with a high sensitivity and a low false positive rate (mean performance metrics: sensitivity = 84.8%, precision = 91.5%, area under precision recall curve = 0.87 and false positive rate = 7.6 per minute). Furthermore, by considering data segments that our network labelled as being predictive, we show that a dip in the beta amplitude (a fall followed by a subsequent rise) is a predictive biomarker for subsequent burst occurrence. Our findings demonstrate proof-of-principle for the feasibility of beta burst prediction and inform the development of a new type of intelligent DBS approach with the capability of stimulating proactively to prevent beta burst occurrence.

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“…The development of aDBS has been recently facilitated by advancements in DBS devices to support bidirectional sensing-stimulation devices, enabling simultaneous stimulation and recording of local eld potential (LFP), both in the clinic and the home environment. LFP activity in the beta frequency band (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) has been most commonly used as the aDBS feedback control signal 5,6 . USe of this signal has been largely based on established evidence that beta activity in both the GPi and STN correlate with PD rigidity and bradykinesia [7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

“…Narrow band gamma activity (70-90Hz) has been suggested as a marker of the 'on medication PD state' and the hyperkinetic state of dyskinesia 13 , and has aslo been successfully used as feedback signals for aDBS. Chronic use of such algorithms over weeks, in patients' home environment, has been shown to potentially improve on-time state and quality of life in most subjects studied 14 . Therefore, aDBS is an approach to improve the e cacy and e ciency of DBS for PD.…”

Section: Introductionmentioning

confidence: 99%

Chronic intracranial recordings in the basal ganglia reveal patient-specific circadian rhythms in Parkinson's disease

de Hemptinne,

Cagle,

de Araujo

et al. 2023

Preprint

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Adaptive deep brain stimulation (aDBS) is a promising therapeutic approach for subjects with Parkinson’s disease (PD) using neural signals as feedback control to adjust the level of therapy. However, the circadian fluctuation of neural signals may alter these control signals and possibly result in suboptimal therapy. We report a large retrospective cohort including 119 subjects with PD (165 hemispheres) with globus pallidus internus (GPi) and subthalamic nucleus (STN) activity recorded chronically in the home environment. Both GPi and STN activity was significantly altered by circadian rhythms. The direction of the circadian rhythm (increase versus decrease at night) depended on the frequency band in both the GPi and STN. The use of long-acting extended released dopaminergic medications significantly impacted the circadian rhythms in the GPi target. These findings demonstrate the variability of chronic circadian rhythms and suggest that aDBS will likely need to account for these patient-specific fluctuations to ensure successful implementation in real-world environments.

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Personalized chronic adaptive deep brain stimulation outperforms conventional stimulation in Parkinson’s disease

Cited by 16 publications

References 65 publications

DBS-induced gamma entrainment as a new biomarker for motor improvement with neuromodulation

DBS-induced gamma entrainment as a new biomarker for motor improvement with neuromodulation

Prediction of pathological subthalamic nucleus beta burst occurrence in Parkinson’s disease

Chronic intracranial recordings in the basal ganglia reveal patient-specific circadian rhythms in Parkinson's disease

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