Modulation of CNS Functions by Deep Brain Stimulation: Insights Provided by Molecular Imaging

Boutet, Alexandre; Jain, Mehr; Gwun, Dave; Rusjan, Pablo; Neudorfer, Clemens; Elias, Gavin J. B.; Germann, Jürgen; Bilbily, Alexander; Kucharczyk, Walter; Fasano, Alfonso; Smith, Gwenn S.; Lozano, Andres M.

doi:10.1007/978-3-030-53168-3_46

Alexandre Boutet^6,7,
Mehr Jain⁶,
Dave Gwun⁶,
Pablo Rusjan⁸,
Clemens Neudorfer⁶,
Gavin J. B. Elias⁶,
Jürgen Germann⁶,
Alexander Bilbily^7,9,6,
Walter Kucharczyk^6,7,
Alfonso Fasano^6,10,11,
Gwenn S. Smith¹² &
…
Andres M. Lozano^6,13

1472 Accesses
4 Citations

Abstract

Deep brain stimulation (DBS) is a neurosurgical intervention that allows probing and recalibration of dysfunctional brain circuits using electrical current delivered via implanted electrodes. While predominantly used in the treatment of Parkinson’s disease and other movement disorders, DBS is increasingly being studied for its application to psychiatric diseases (e.g., major depressive disorder and obsessive-compulsive disorder) and cognitive disorders (e.g., Alzheimer’s disease). Despite these growing applications of DBS, the mechanisms of action underlying DBS are poorly understood. Molecular neuroimaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) provide a unique window into the neural changes induced by electrical stimulation; as such, they constitute invaluable research tools, with the potential to dramatically enhance both our understanding of this technology and its therapeutic impact. This chapter aims to provide an up-to-date review of insights gleaned from PET and SPECT studies in DBS patients.

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Abbreviations

[¹¹C]dMP:: [¹¹C]d-Threo-methylphenidate
[¹¹C]DTBZ:: [¹¹C]Dihydrotetrabenazine
[¹¹C]NEM:: [¹¹C]Nemonapride
[¹¹C]RACLO:: [¹¹C]Raclopride
[¹²³I]FP-CIT:: N-ω-Fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)tropane
[¹²³I]IBZM:: [¹²³I]Iodobenzamide
[¹²³I]IMP:: N-Isopropyl-p-(iodine-123)-iodoamphetamine
[¹⁸F]FDG:: 18-Fluoro-2-deoxyglucose
[¹⁸F]FDOPA:: L-6-[¹⁸F]Fluoro-3,4-dihydroxyphenylalanine
[¹⁸F]FP:: [¹⁸F]Fallypride
[^99mTc]ECD:: ^99mTechnetium-ethylene biyldicysteinate dimer
[^99mTc]HMPAO:: ^99mTechnetium hexamethyl
ACC:: Anterior cingulate cortex
AD:: Alzheimer’s disease
BOLD:: Blood-oxygenation-level-dependent
CSTC:: Cortico-striato-thalamo-cortical
DBS:: Deep brain stimulation
fMRI:: Functional magnetic resonance imaging
GPi:: Globus pallidus internus
MDD:: Major depressive disorder
MRI:: Magnetic resonance imaging
NAcc:: Nucleus accumbens
OCD:: Obsessive-compulsive disorder
PCC:: Posterior cingulate cortex
PD:: Parkinson’s disease
PDRP:: Parkinson’s disease-related pattern
PET:: Positron emission tomography
SGC:: Subgenual cingulate cortex
SMA:: Supplementary motor area
SPECT:: Single-photon emission computed tomography
STN:: Subthalamic nucleus

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Conflicts of Interest

Dr. Bilbily is the co-founder and CEO of 16 Bit Inc. Dr. Fasano reports grants, personal fees, and nonfinancial support from AbbVie; grants, personal fees, and nonfinancial support from Medtronic; grants and personal fees from Boston Scientific; personal fees from Sunovion; personal fees from Chiesi Farmaceutici, personal fees from UCB; and grants and personal fees from Ipsen, outside the submitted work. Dr. Lozano serves as a consultant for Medtronic, Abbott, Boston Scientific, and Functional Neuromodulation, during the conduct of the study, and reports grants from GE Healthcare, outside the submitted work. Other authors report no conflict of interest.

Funding: This chapter was supported by the RR Tasker Chair in Functional Neurosurgery at University Health Network and a Tier 1 Canada Research Chair in Neuroscience and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG NE 2276/1-1) (C.N.). The corresponding author confirms that he had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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University Health Network, Toronto, ON, Canada
Alexandre Boutet, Mehr Jain, Dave Gwun, Clemens Neudorfer, Gavin J. B. Elias, Jürgen Germann, Alexander Bilbily, Walter Kucharczyk, Alfonso Fasano & Andres M. Lozano
Joint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada
Alexandre Boutet, Alexander Bilbily & Walter Kucharczyk
Research and Imaging Centre and Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health, Toronto, ON, Canada
Pablo Rusjan
16 Bit Inc., Toronto, ON, Canada
Alexander Bilbily
Edmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, ON, Canada
Alfonso Fasano
Krembil Brain Institute, Toronto, ON, Canada
Alfonso Fasano
Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore, MD, USA
Gwenn S. Smith
Division of Neurosurgery, Toronto Western Hospital, Toronto, ON, Canada
Andres M. Lozano

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Alexandre Boutet
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Mehr Jain
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Dave Gwun
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Pablo Rusjan
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Clemens Neudorfer
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Gavin J. B. Elias
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Jürgen Germann
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Alexander Bilbily
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Walter Kucharczyk
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Alfonso Fasano
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Gwenn S. Smith
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Andres M. Lozano
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Correspondence to Andres M. Lozano .

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Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands
Rudi A. J. O. Dierckx
Faculty of Electrical Engineering, Medical Engineering and Computer Science, Offenburg University, Offenburg, Germany
Andreas Otte
Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands
Erik F. J. de Vries
Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands
Aren van Waarde
Neurology, University Medical Center Groningen, Groningen, The Netherlands
Klaus L. Leenders

Appendix

1.1 Abbreviations Used in Tables

a Anterior

Amy Amygdala

AnG Angular gyrus

BA Broca’s area

BG Basal ganglia

Br Brain stem

c Caudal

CC Cingulate cortex

CdN Caudate nucleus

Cereb Cerebellum

Cl Claustrum

CUN Cuneus

d Dorsal

DMN Default mode network

FG Frontal gyrus

FO Frontal operculum

FPC Frontopolar cortex

FS Frontal sulcus

FuG Fusiform gyrus

GP Globus pallidus

GPe Globus pallidus externus

GPi Globus pallidus internus

Hi Hippocampus

hThal Hypothalamus

i Inferior

IC Internal capsule

INS Insula

l Lateral

LC Limbic cortex

LenN Lentiform nucleus

LG Lingual gyrus

m Middle

me Medial

MidB Midbrain

NAcc Nucleus accumbens

NuB Nucleus basalis

OC Occipital cortex

OFC Orbitofrontal cortex

p Posterior

PAC Parietal association cortex

PAG Periaqueductal gray

PAL Pallidum

pAuC/sAuC Primary/secondary auditory cortex

PCUN Precuneus

PFC Prefrontal cortex

pHi Parahippocampus

PL Parietal lobe

PMC Premotor cortex

Po Pons

PoG Postcentral gyrus

PPN Pedunculopontine nucleus

PPO Postcentral parietal operculum

PrG Precentral gyrus

PTC Parietotemporal cortex

Pu Putamen

PVG Periventricular gray

r Rostral

RC Retrosplenial cortex

RN Red nucleus

s Superior

SAA Sensory association area

SG Subgenual

SMA Supplementary motor cortex

SMG Supramarginal gyrus

SN Substantia nigra

Str Striatum

TAC Temporal association cortex

TG Temporal gyrus

Thal Thalamus (includes all parts of the thalamus)

TN Trigeminal nucleus

TPJ Temporoparietal junction

TPo Temporal pole

Un Uncus

v Ventral

WA Wernicke’s area

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Boutet, A. et al. (2021). Modulation of CNS Functions by Deep Brain Stimulation: Insights Provided by Molecular Imaging. In: Dierckx, R.A.J.O., Otte, A., de Vries, E.F.J., van Waarde, A., Leenders, K.L. (eds) PET and SPECT in Neurology. Springer, Cham. https://doi.org/10.1007/978-3-030-53168-3_46

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DOI: https://doi.org/10.1007/978-3-030-53168-3_46
Published: 11 October 2020
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Print ISBN: 978-3-030-53167-6
Online ISBN: 978-3-030-53168-3
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