Controlling Clinical States Governed by Different Temporal Dynamics With Closed-Loop Deep Brain Stimulation: A Principled Framework

Tinkhauser, Gerd; Moraud, Eduardo Martin

doi:10.3389/fnins.2021.734186

Cited by 27 publications

(53 citation statements)

References 93 publications

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“…We predict that this understanding will open new possibilities to design algorithms that decode gait deficits in people with PD. These predictions will support strategies that translate continuous recordings of STN LFP into control commands to operate neuromodulation therapies in closed loop at multiple time scales ( 60 ). Similar approaches may be extended to other brain structures (internal globus pallidus or the pedunculopontine nucleus) or other neurological disorders.…”

Section: Discussionmentioning

confidence: 88%

Principles of gait encoding in the subthalamic nucleus of people with Parkinson’s disease

et al. 2022

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Disruption of subthalamic nucleus dynamics in Parkinson’s disease leads to impairments during walking. Here, we aimed to uncover the principles through which the subthalamic nucleus encodes functional and dysfunctional walking in people with Parkinson’s disease. We conceived a neurorobotic platform embedding an isokinetic dynamometric chair that allowed us to deconstruct key components of walking under well-controlled conditions. We exploited this platform in 18 patients with Parkinson’s disease to demonstrate that the subthalamic nucleus encodes the initiation, termination, and amplitude of leg muscle activation. We found that the same fundamental principles determine the encoding of leg muscle synergies during standing and walking. We translated this understanding into a machine learning framework that decoded muscle activation, walking states, locomotor vigor, and freezing of gait. These results expose key principles through which subthalamic nucleus dynamics encode walking, opening the possibility to operate neuroprosthetic systems with these signals to improve walking in people with Parkinson’s disease.

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Section: Discussionmentioning

confidence: 88%

Principles of gait encoding in the subthalamic nucleus of people with Parkinson’s disease

et al. 2022

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“…Moreover, it would be interesting to simulate the action of DBS as in [ 95 – 98 ] also in our model to evaluate its effects on suppressing β oscillations and compare these to experimental results [ 99 – 101 ]. Recent studies highlighted a dynamical and functional distinction between a low β range [12–20] Hz and a high β range [20–30] Hz [ 102 – 104 ].…”

Section: Discussionmentioning

confidence: 99%

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

Ortone¹,

Vergani²,

Ahmadipour³

et al. 2023

PLoS Comput Biol

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Motor symptoms of Parkinson’s Disease (PD) are associated with dopamine deficits and pathological oscillation of basal ganglia (BG) neurons in the β range ([12-30] Hz). However, how dopamine depletion affects the oscillation dynamics of BG nuclei is still unclear. With a spiking neurons model, we here capture the features of BG nuclei interactions leading to oscillations in dopamine-depleted condition. We highlight that both the loop between subthalamic nucleus (STN) and Globus Pallidus pars externa (GPe) and the loop between striatal fast spiking and medium spiny neurons and GPe display resonances in the β range, and synchronize to a common β frequency through interaction. Crucially, the synchronization depends on dopamine depletion: the two loops are largely independent for high levels of dopamine, but progressively synchronize as dopamine is depleted due to the increased strength of the striatal loop. The model is validated against recent experimental reports on the role of cortical inputs, STN and GPe activity in the generation of β oscillations. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustained β oscillations in PD subjects, and explain how this interplay depends on the level of dopamine. This paves the way to the design of therapies specifically addressing the onset of pathological β oscillations.

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“…For instance, the dopamine depletion values in our model could both increase due to the progression of PD and decrease due to the action of dopamine agonists, but to proper model this latter aspect we have to take into account several other pathophysiological aspects [73]. Moreover, it would be interesting to simulate the action of Deep Brain stimulation as in [67,[74][75][76] also in our network to evaluate the input of different targets on suppressing the β oscillations and compare it to experimental results [77][78][79].…”

Section: Discussionmentioning

confidence: 99%

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

Ortone

Vergani

Mannella

et al. 2022

Preprint

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Motor symptoms of Parkinson's Disease (PD) are associated with dopamine deficits and pathological oscillation of basal ganglia (BG) neurons in the beta range ([12-30] Hz). However, how the dopamine depletion affects the oscillation dynamics of BG nuclei is still unclear. With a spiking neurons model, we here captured the features of BG nuclei interactions leading to oscillations in dopamine-depleted condition. We found that both the loop between subthalamic nucleus and Globus Pallidus pars externa (GPe) and the loop between striatal fast spiking and medium spiny neurons and GPe displayed resonances in the beta range, and synchronized to a common beta frequency through interaction. Crucially, the synchronization depends on dopamine depletion: the two loops were largely independent for high levels of dopamine, but progressively synchronized as dopamine was depleted due to the increased strength of the striatal loop. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustained beta oscillations in PD subjects, and explain how this interplay depends on the level of dopamine. This paves the way to the design of therapies specifically addressing the onset of pathological beta oscillations.

show abstract

Controlling Clinical States Governed by Different Temporal Dynamics With Closed-Loop Deep Brain Stimulation: A Principled Framework

Cited by 27 publications

References 93 publications

Principles of gait encoding in the subthalamic nucleus of people with Parkinson’s disease

Principles of gait encoding in the subthalamic nucleus of people with Parkinson’s disease

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

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