Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease

Research output: Contribution to journalArticle

Abstract

Introduction: Deep brain stimulation (DBS) is an established treatment Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of STN DBS in PD on the dopamine system and neural circuitry employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease striatal VMAT2, secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical metabolism. Methods: PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4–6 months of STN stimulation in seven PD patients (mean age 67 ± 7). Results: The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism. Conclusions: The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.

Original languageEnglish (US)
JournalParkinsonism and Related Disorders
DOIs
StatePublished - Jan 1 2019

Fingerprint

Vesicular Monoamine Transport Proteins
Corpus Striatum
Thalamic Nuclei
Deep Brain Stimulation
Parkinson Disease
Glucose
Positron-Emission Tomography
Dopamine
Parietal Lobe
Putamen
Temporal Lobe
Cerebellum
Depression

Keywords

  • Deep brain stimulation
  • Dopamine
  • Glucose metabolism
  • Parkinson's disease
  • Positron emission tomography (PET)
  • Sub-thalamic nucleus
  • VMAT2

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

@article{71e88006a8e74efc970aabbf9b715bda,
title = "Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease",
abstract = "Introduction: Deep brain stimulation (DBS) is an established treatment Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of STN DBS in PD on the dopamine system and neural circuitry employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease striatal VMAT2, secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical metabolism. Methods: PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4–6 months of STN stimulation in seven PD patients (mean age 67 ± 7). Results: The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism. Conclusions: The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.",
keywords = "Deep brain stimulation, Dopamine, Glucose metabolism, Parkinson's disease, Positron emission tomography (PET), Sub-thalamic nucleus, VMAT2",
author = "Gwenn Smith and Kelly Mills and Pontone, {Gregory M} and Anderson, {William S} and Perepezko, {Kate M.} and Brasic, {James R} and Yun Zhou and Jason Brandt and Butson, {Christopher R.} and Daniel Holt and Mathews, {William B} and Dannals, {Robert F} and Wong, {Dean Foster} and Zoltan Mari",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.parkreldis.2019.04.006",
language = "English (US)",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
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}

TY - JOUR

T1 - Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease

AU - Smith, Gwenn

AU - Mills, Kelly

AU - Pontone, Gregory M

AU - Anderson, William S

AU - Perepezko, Kate M.

AU - Brasic, James R

AU - Zhou, Yun

AU - Brandt, Jason

AU - Butson, Christopher R.

AU - Holt, Daniel

AU - Mathews, William B

AU - Dannals, Robert F

AU - Wong, Dean Foster

AU - Mari, Zoltan

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: Deep brain stimulation (DBS) is an established treatment Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of STN DBS in PD on the dopamine system and neural circuitry employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease striatal VMAT2, secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical metabolism. Methods: PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4–6 months of STN stimulation in seven PD patients (mean age 67 ± 7). Results: The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism. Conclusions: The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.

AB - Introduction: Deep brain stimulation (DBS) is an established treatment Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of STN DBS in PD on the dopamine system and neural circuitry employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease striatal VMAT2, secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical metabolism. Methods: PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4–6 months of STN stimulation in seven PD patients (mean age 67 ± 7). Results: The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism. Conclusions: The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.

KW - Deep brain stimulation

KW - Dopamine

KW - Glucose metabolism

KW - Parkinson's disease

KW - Positron emission tomography (PET)

KW - Sub-thalamic nucleus

KW - VMAT2

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U2 - 10.1016/j.parkreldis.2019.04.006

DO - 10.1016/j.parkreldis.2019.04.006

M3 - Article

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

SN - 1353-8020

ER -