Modeling Parkinsonian Circuitry and the DBS Electrode

Arle, Jeffrey E.; Mei, Longzhi; Shils, Jay L.

doi:10.1159/000108584

Cited by 20 publications

(26 citation statements)

References 84 publications

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“…and is described elsewhere. 71,72 It allows us to simulate general biophysics of each neuron on a conductance level, connect thousands of such independent cells together, each with electrotonic dendritic processing, and keep track of each synaptic event and time step on a 0.25 ms timescale.…”

Section: Modeling Techniquementioning

confidence: 99%

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Motor Cortex Stimulation for Pain and Movement Disorders

Arle

Shils

2008

Neurotherapeutics

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Summary:Since initial reports in the early 1990s, stimulation of the M1 region of the cortex (MCS) has been used to treat chronic refractory pain conditions and a variety of movement disorders. A Medline search of literature between 1991 and 2007 revealed 512 cases using MCS. Although most of these relate to the treatment of pain (422), 84 of them involve movement disorders. More recently, several studies have specifically looked at treating Parkinson's disease (PD) with MCS. We report here several of our own cases using MCS to treat poststroke and non-poststroke pain syndromes and movement disorders (n ϭ 8), PD (n ϭ 4), ET (n ϭ 2), and cortico-basal degeneration (n ϭ 1). We also cover the essential history of this procedure and our current research using computational modeling to understand further the underlying mechanisms of MCS.

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Section: Modeling Techniquementioning

confidence: 99%

“…Schematic showing all of the interconnections of two regions of cortex simulated using the UNCuS software program 71,72 and regions of sensory and motor thalamus used to model pain processing and the effect of motor cortex stimulation (MCS) on S1. Arrows in red indicate inhibitory synapses on their targets; those in green, excitatory.…”

Section: Figmentioning

confidence: 99%

Motor Cortex Stimulation for Pain and Movement Disorders

Arle

Shils

2008

Neurotherapeutics

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“…Simulations were run on UNCuS, details of which have been published previously [21,22,23] and with a custom program written in C++ (Microsoft Visual Studio; Microsoft, Redmond, WA, USA) and Java (Oracle Corp., Redwood City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…This DBS-activated FF is based on the frequency of the DBS electrode ( f DBS ), the average firing rate of the presynaptic cell ( f- c ), the AP speed of propagation ( V AP ) which accounts for fiber diameter and myelination together, the location along the axon of the maximum AF value ( maxAF , L maxAF ), and the refractory time of the axon ( T r ). We corroborated this function by simulating an axon of arbitrary thickness and myelination passing through an arbitrary DBS field using neural circuitry simulation software [21]. Given this geometry, we were able to calculate the entire distribution of the AF (Fig.…”

Section: Introductionmentioning

confidence: 99%

Theoretical Effect of DBS on Axonal Fibers of Passage: Firing Rates, Entropy, and Information Content

Arle¹,

Mei

Carlson

et al. 2018

Stereotact Funct Neurosurg

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Background: Deep brain stimulation (DBS) has effects on axons that originate and terminate outside the DBS target area. Objective: We hypothesized that DBS generates action potentials (APs) in both directions in “axons of passage,” altering their information content and that of all downstream cells and circuits, and sought to quantify the change in fiber information content. Methods: We incorporated DBS parameters (fiber firing frequency and refractory time, and AP initiation location along the fiber and propagation velocity) in a filtering function determining the AP frequency reaching the postsynaptic cell. Using neural circuitry simulation software, we investigated the ability of the filtering function to predict the firing frequency of APs reaching neurons targeted by axons of passage. We calculated their entropy with and without DBS, and with the electrode applied at various distances from the cell body. Results: The predictability of the filtering function exceeded 98%. Entropy calculations showed that the entropy ratio “without DBS” to “with DBS” was always >1.0, thus DBS reduces fiber entropy. Conclusions: (1) The results imply that DBS effects are due to entropy reduction within fibers, i.e., a reduction in their information. (2) Where fibers of passage do not terminate in target regions, DBS may have side effects on nontargeted circuitry.

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“…1). Although the exact mechanism of action of DBS is not known and challenging to study in humans, it has both excitatory and inhibitory local effects, as well as widespread network influence, which together can result in symptomatic improvement in a particular disease, most commonly a movement disorder [1][2][3][4][5]. DBS has become the gold standard treatment for many of the most common movement disorders when pharmacologic therapies fail to adequately control symptoms, are not tolerated owing to side effects, or result in motor complications [6,7].…”

mentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders

Larson

2014

Neurotherapeutics

111

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Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low-generally ≤ 5% at experienced, large-volume centers. It has been used widely in essential tremor, Parkinson's disease, and dystonia when medical treatment becomes ineffective, intolerable owing to side effects, or causes motor complications. Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson's disease), and globus pallidus (Parkinson's disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of "closed loop" stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery.

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Modeling Parkinsonian Circuitry and the DBS Electrode

Cited by 20 publications

References 84 publications

Motor Cortex Stimulation for Pain and Movement Disorders

Motor Cortex Stimulation for Pain and Movement Disorders

Theoretical Effect of DBS on Axonal Fibers of Passage: Firing Rates, Entropy, and Information Content

Deep Brain Stimulation for Movement Disorders

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