Clinical deep brain stimulation strategies for orientation-selective pathway activation

Julia P. Slopsema, Edgar Peña, Remi Patriat, Lauri J Lehto, Olli Gröhn, Silvia Mangia, Noam Harel, Shalom Michaeli, Matthew D Johnson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective. This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants. Approach. Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain. Orientation-selective pulse paradigms were evaluated in conceptual models and in patient-specific models of subthalamic nucleus (STN)-DBS for treating Parkinson's disease. Main results. Single-contact monopolar or two-contact bipolar stimulation through clinical DBS leads with cylindrical electrodes primarily activated axons orientated parallel to the lead. Conversely, multi-contact monopolar stimulation with a cathode-leading pulse waveform selectively activated axons perpendicular to the DBS lead. Clinical DBS leads with segmented rows of electrodes and a single current source provided additional angular resolution for activating axons oriented 0°, ±22.5°, ±45°, ±67.5°, or 90° relative to the lead shaft. Employing multiple independent current sources to deliver unequal amounts of current through these leads further increased the angular resolution of activation relative to the lead shaft. The patient-specific models indicated that multi-contact cathode configurations, which are rarely used in clinical practice, could increase activation of the hyperdirect pathway collaterals projecting into STN (a putative therapeutic target), while minimizing direct activation of the corticospinal tract of internal capsule, which can elicit sensorimotor side-effects when stimulated. Significance. When combined with patient-specific tissue anisotropy and patient-specific anatomical morphologies of neural pathways responsible for therapy and side effects, orientation-selective DBS approaches show potential to significantly improve clinical outcomes of DBS therapy for a range of existing and investigational clinical indications.

Original languageEnglish (US)
Article number056029
JournalJournal of neural engineering
Volume15
Issue number5
DOIs
StatePublished - Sep 5 2018

Fingerprint

Deep Brain Stimulation
Brain
Chemical activation
Electrodes
Axons
Subthalamic Nucleus
Lead
Internal Capsule
Cathodes
Neural Pathways
Pyramidal Tracts
Electric fields
Anisotropy
Parkinson Disease
Therapeutics
Tissue

Keywords

  • axonal pathways
  • brain disorders
  • computational modeling
  • deep brain stimulation
  • orientation selectivity
  • pulse patterns
  • therapeutic window

PubMed: MeSH publication types

  • Journal Article

Cite this

Clinical deep brain stimulation strategies for orientation-selective pathway activation. / Slopsema, Julia P.; Peña, Edgar; Patriat, Remi; Lehto, Lauri J; Gröhn, Olli; Mangia, Silvia; Harel, Noam; Michaeli, Shalom; Johnson, Matthew D.

In: Journal of neural engineering, Vol. 15, No. 5, 056029, 05.09.2018.

Research output: Contribution to journalArticle

@article{76eb03951b3b485cb0fd775656d04df8,
title = "Clinical deep brain stimulation strategies for orientation-selective pathway activation",
abstract = "Objective. This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants. Approach. Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain. Orientation-selective pulse paradigms were evaluated in conceptual models and in patient-specific models of subthalamic nucleus (STN)-DBS for treating Parkinson's disease. Main results. Single-contact monopolar or two-contact bipolar stimulation through clinical DBS leads with cylindrical electrodes primarily activated axons orientated parallel to the lead. Conversely, multi-contact monopolar stimulation with a cathode-leading pulse waveform selectively activated axons perpendicular to the DBS lead. Clinical DBS leads with segmented rows of electrodes and a single current source provided additional angular resolution for activating axons oriented 0°, ±22.5°, ±45°, ±67.5°, or 90° relative to the lead shaft. Employing multiple independent current sources to deliver unequal amounts of current through these leads further increased the angular resolution of activation relative to the lead shaft. The patient-specific models indicated that multi-contact cathode configurations, which are rarely used in clinical practice, could increase activation of the hyperdirect pathway collaterals projecting into STN (a putative therapeutic target), while minimizing direct activation of the corticospinal tract of internal capsule, which can elicit sensorimotor side-effects when stimulated. Significance. When combined with patient-specific tissue anisotropy and patient-specific anatomical morphologies of neural pathways responsible for therapy and side effects, orientation-selective DBS approaches show potential to significantly improve clinical outcomes of DBS therapy for a range of existing and investigational clinical indications.",
keywords = "axonal pathways, brain disorders, computational modeling, deep brain stimulation, orientation selectivity, pulse patterns, therapeutic window",
author = "Slopsema, {Julia P.} and Edgar Pe{\~n}a and Remi Patriat and Lehto, {Lauri J} and Olli Gr{\"o}hn and Silvia Mangia and Noam Harel and Shalom Michaeli and Johnson, {Matthew D}",
year = "2018",
month = "9",
day = "5",
doi = "10.1088/1741-2552/aad978",
language = "English (US)",
volume = "15",
journal = "Journal of Neural Engineering",
issn = "1741-2560",
publisher = "IOP Publishing Ltd.",
number = "5",

}

TY - JOUR

T1 - Clinical deep brain stimulation strategies for orientation-selective pathway activation

AU - Slopsema, Julia P.

AU - Peña, Edgar

AU - Patriat, Remi

AU - Lehto, Lauri J

AU - Gröhn, Olli

AU - Mangia, Silvia

AU - Harel, Noam

AU - Michaeli, Shalom

AU - Johnson, Matthew D

PY - 2018/9/5

Y1 - 2018/9/5

N2 - Objective. This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants. Approach. Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain. Orientation-selective pulse paradigms were evaluated in conceptual models and in patient-specific models of subthalamic nucleus (STN)-DBS for treating Parkinson's disease. Main results. Single-contact monopolar or two-contact bipolar stimulation through clinical DBS leads with cylindrical electrodes primarily activated axons orientated parallel to the lead. Conversely, multi-contact monopolar stimulation with a cathode-leading pulse waveform selectively activated axons perpendicular to the DBS lead. Clinical DBS leads with segmented rows of electrodes and a single current source provided additional angular resolution for activating axons oriented 0°, ±22.5°, ±45°, ±67.5°, or 90° relative to the lead shaft. Employing multiple independent current sources to deliver unequal amounts of current through these leads further increased the angular resolution of activation relative to the lead shaft. The patient-specific models indicated that multi-contact cathode configurations, which are rarely used in clinical practice, could increase activation of the hyperdirect pathway collaterals projecting into STN (a putative therapeutic target), while minimizing direct activation of the corticospinal tract of internal capsule, which can elicit sensorimotor side-effects when stimulated. Significance. When combined with patient-specific tissue anisotropy and patient-specific anatomical morphologies of neural pathways responsible for therapy and side effects, orientation-selective DBS approaches show potential to significantly improve clinical outcomes of DBS therapy for a range of existing and investigational clinical indications.

AB - Objective. This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants. Approach. Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain. Orientation-selective pulse paradigms were evaluated in conceptual models and in patient-specific models of subthalamic nucleus (STN)-DBS for treating Parkinson's disease. Main results. Single-contact monopolar or two-contact bipolar stimulation through clinical DBS leads with cylindrical electrodes primarily activated axons orientated parallel to the lead. Conversely, multi-contact monopolar stimulation with a cathode-leading pulse waveform selectively activated axons perpendicular to the DBS lead. Clinical DBS leads with segmented rows of electrodes and a single current source provided additional angular resolution for activating axons oriented 0°, ±22.5°, ±45°, ±67.5°, or 90° relative to the lead shaft. Employing multiple independent current sources to deliver unequal amounts of current through these leads further increased the angular resolution of activation relative to the lead shaft. The patient-specific models indicated that multi-contact cathode configurations, which are rarely used in clinical practice, could increase activation of the hyperdirect pathway collaterals projecting into STN (a putative therapeutic target), while minimizing direct activation of the corticospinal tract of internal capsule, which can elicit sensorimotor side-effects when stimulated. Significance. When combined with patient-specific tissue anisotropy and patient-specific anatomical morphologies of neural pathways responsible for therapy and side effects, orientation-selective DBS approaches show potential to significantly improve clinical outcomes of DBS therapy for a range of existing and investigational clinical indications.

KW - axonal pathways

KW - brain disorders

KW - computational modeling

KW - deep brain stimulation

KW - orientation selectivity

KW - pulse patterns

KW - therapeutic window

UR - http://www.scopus.com/inward/record.url?scp=85053144098&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053144098&partnerID=8YFLogxK

U2 - 10.1088/1741-2552/aad978

DO - 10.1088/1741-2552/aad978

M3 - Article

VL - 15

JO - Journal of Neural Engineering

JF - Journal of Neural Engineering

SN - 1741-2560

IS - 5

M1 - 056029

ER -