Dissecting Brainstem Locomotor Circuits: Converging Evidence for Cuneiform Nucleus Stimulation

Stephano J. Chang; Iahn Cajigas; Ioan Opris; James D. Guest; Brian R. Noga

doi:10.3389/fnsys.2020.00064

Dissecting Brainstem Locomotor Circuits: Converging Evidence for Cuneiform Nucleus Stimulation

Stephano J. Chang, Iahn Cajigas, Ioan Opris, James D. Guest, Brian R. Noga

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

There are a pressing and unmet need for effective therapies for freezing of gait (FOG) and other neurological gait disorders. Deep brain stimulation (DBS) of a midbrain target known as the pedunculopontine nucleus (PPN) was proposed as a potential treatment based on its postulated involvement in locomotor control as part of the mesencephalic locomotor region (MLR). However, DBS trials fell short of expectations, leading many clinicians to abandon this strategy. Here, we discuss the potential reasons for this failure and review recent clinical data along with preclinical optogenetics evidence to argue that another nearby nucleus, the cuneiform nucleus (CnF), may be a superior target.

Original language	English (US)
Article number	64
Journal	Frontiers in Systems Neuroscience
Volume	14
DOIs	https://doi.org/10.3389/fnsys.2020.00064
State	Published - Aug 21 2020

Keywords

cuneiform nucleus
deep brain stimulation
gait dysfunction
mesencephalic locomotor region
pedunculopontine nucleus

ASJC Scopus subject areas

Neuroscience (miscellaneous)
Developmental Neuroscience
Cognitive Neuroscience
Cellular and Molecular Neuroscience

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10.3389/fnsys.2020.00064

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title = "Dissecting Brainstem Locomotor Circuits: Converging Evidence for Cuneiform Nucleus Stimulation",

abstract = "There are a pressing and unmet need for effective therapies for freezing of gait (FOG) and other neurological gait disorders. Deep brain stimulation (DBS) of a midbrain target known as the pedunculopontine nucleus (PPN) was proposed as a potential treatment based on its postulated involvement in locomotor control as part of the mesencephalic locomotor region (MLR). However, DBS trials fell short of expectations, leading many clinicians to abandon this strategy. Here, we discuss the potential reasons for this failure and review recent clinical data along with preclinical optogenetics evidence to argue that another nearby nucleus, the cuneiform nucleus (CnF), may be a superior target.",

keywords = "cuneiform nucleus, deep brain stimulation, gait dysfunction, mesencephalic locomotor region, pedunculopontine nucleus",

author = "Chang, {Stephano J.} and Iahn Cajigas and Ioan Opris and Guest, {James D.} and Noga, {Brian R.}",

note = "Funding Information: We would like to thank Francisco Sanchez and Luz Villamil for their support and helpful contributions to this research. Funding. This work was supported by the National Institutes of Neurological Disorders and Stroke (NINDS) grant R01 NS089972 and U.S. Department of Defense (DOD) award SCI140238. SC was supported by a research fellowship from the Neurosurgery Research and Education Foundation (GR010471). Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Chang, Cajigas, Opris, Guest and Noga.",

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doi = "10.3389/fnsys.2020.00064",

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AU - Chang, Stephano J.

AU - Cajigas, Iahn

AU - Opris, Ioan

AU - Guest, James D.

AU - Noga, Brian R.

N1 - Funding Information: We would like to thank Francisco Sanchez and Luz Villamil for their support and helpful contributions to this research. Funding. This work was supported by the National Institutes of Neurological Disorders and Stroke (NINDS) grant R01 NS089972 and U.S. Department of Defense (DOD) award SCI140238. SC was supported by a research fellowship from the Neurosurgery Research and Education Foundation (GR010471). Publisher Copyright: © Copyright © 2020 Chang, Cajigas, Opris, Guest and Noga.

PY - 2020/8/21

Y1 - 2020/8/21

N2 - There are a pressing and unmet need for effective therapies for freezing of gait (FOG) and other neurological gait disorders. Deep brain stimulation (DBS) of a midbrain target known as the pedunculopontine nucleus (PPN) was proposed as a potential treatment based on its postulated involvement in locomotor control as part of the mesencephalic locomotor region (MLR). However, DBS trials fell short of expectations, leading many clinicians to abandon this strategy. Here, we discuss the potential reasons for this failure and review recent clinical data along with preclinical optogenetics evidence to argue that another nearby nucleus, the cuneiform nucleus (CnF), may be a superior target.

AB - There are a pressing and unmet need for effective therapies for freezing of gait (FOG) and other neurological gait disorders. Deep brain stimulation (DBS) of a midbrain target known as the pedunculopontine nucleus (PPN) was proposed as a potential treatment based on its postulated involvement in locomotor control as part of the mesencephalic locomotor region (MLR). However, DBS trials fell short of expectations, leading many clinicians to abandon this strategy. Here, we discuss the potential reasons for this failure and review recent clinical data along with preclinical optogenetics evidence to argue that another nearby nucleus, the cuneiform nucleus (CnF), may be a superior target.

KW - cuneiform nucleus

KW - deep brain stimulation

KW - gait dysfunction

KW - mesencephalic locomotor region

KW - pedunculopontine nucleus

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Dissecting Brainstem Locomotor Circuits: Converging Evidence for Cuneiform Nucleus Stimulation

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Keywords

ASJC Scopus subject areas

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