Thalamic metabolism and symptom onset in preclinical Huntington's disease

A. Feigin, C. Tang, Y. Ma, P. Mattis, D. Zgaljardic, M. Guttman, J. S. Paulsen, V. Dhawan, D. Eidelberg

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [ 18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P <0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P <0.003) but declined at 44 months (P <0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P <0.01). Striatal metabolism was abnormally low at all time points (P <0.005). By contrast, thalamic metabolism was elevated at baseline (P <0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.

Original languageEnglish (US)
Pages (from-to)2858-2867
Number of pages10
JournalBrain
Volume130
Issue number11
DOIs
StatePublished - Nov 2007

Fingerprint

Huntington Disease
Corpus Striatum
Positron-Emission Tomography
Raclopride
Fluorodeoxyglucose F18
Metabolic Networks and Pathways
Genes
Atrophy
Glucose

Keywords

  • Brain metabolism
  • Positron emission tomography (PET)
  • Preclinical Huntington's disease (p-HD)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Feigin, A., Tang, C., Ma, Y., Mattis, P., Zgaljardic, D., Guttman, M., ... Eidelberg, D. (2007). Thalamic metabolism and symptom onset in preclinical Huntington's disease. Brain, 130(11), 2858-2867. https://doi.org/10.1093/brain/awm217

Thalamic metabolism and symptom onset in preclinical Huntington's disease. / Feigin, A.; Tang, C.; Ma, Y.; Mattis, P.; Zgaljardic, D.; Guttman, M.; Paulsen, J. S.; Dhawan, V.; Eidelberg, D.

In: Brain, Vol. 130, No. 11, 11.2007, p. 2858-2867.

Research output: Contribution to journalArticle

Feigin, A, Tang, C, Ma, Y, Mattis, P, Zgaljardic, D, Guttman, M, Paulsen, JS, Dhawan, V & Eidelberg, D 2007, 'Thalamic metabolism and symptom onset in preclinical Huntington's disease', Brain, vol. 130, no. 11, pp. 2858-2867. https://doi.org/10.1093/brain/awm217
Feigin A, Tang C, Ma Y, Mattis P, Zgaljardic D, Guttman M et al. Thalamic metabolism and symptom onset in preclinical Huntington's disease. Brain. 2007 Nov;130(11):2858-2867. https://doi.org/10.1093/brain/awm217
Feigin, A. ; Tang, C. ; Ma, Y. ; Mattis, P. ; Zgaljardic, D. ; Guttman, M. ; Paulsen, J. S. ; Dhawan, V. ; Eidelberg, D. / Thalamic metabolism and symptom onset in preclinical Huntington's disease. In: Brain. 2007 ; Vol. 130, No. 11. pp. 2858-2867.
@article{4b104b63ff404581beaaa51f150d23c0,
title = "Thalamic metabolism and symptom onset in preclinical Huntington's disease",
abstract = "The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [ 18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P <0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P <0.003) but declined at 44 months (P <0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P <0.01). Striatal metabolism was abnormally low at all time points (P <0.005). By contrast, thalamic metabolism was elevated at baseline (P <0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.",
keywords = "Brain metabolism, Positron emission tomography (PET), Preclinical Huntington's disease (p-HD)",
author = "A. Feigin and C. Tang and Y. Ma and P. Mattis and D. Zgaljardic and M. Guttman and Paulsen, {J. S.} and V. Dhawan and D. Eidelberg",
year = "2007",
month = "11",
doi = "10.1093/brain/awm217",
language = "English (US)",
volume = "130",
pages = "2858--2867",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Thalamic metabolism and symptom onset in preclinical Huntington's disease

AU - Feigin, A.

AU - Tang, C.

AU - Ma, Y.

AU - Mattis, P.

AU - Zgaljardic, D.

AU - Guttman, M.

AU - Paulsen, J. S.

AU - Dhawan, V.

AU - Eidelberg, D.

PY - 2007/11

Y1 - 2007/11

N2 - The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [ 18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P <0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P <0.003) but declined at 44 months (P <0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P <0.01). Striatal metabolism was abnormally low at all time points (P <0.005). By contrast, thalamic metabolism was elevated at baseline (P <0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.

AB - The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [ 18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P <0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P <0.003) but declined at 44 months (P <0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P <0.01). Striatal metabolism was abnormally low at all time points (P <0.005). By contrast, thalamic metabolism was elevated at baseline (P <0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.

KW - Brain metabolism

KW - Positron emission tomography (PET)

KW - Preclinical Huntington's disease (p-HD)

UR - http://www.scopus.com/inward/record.url?scp=35648963039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35648963039&partnerID=8YFLogxK

U2 - 10.1093/brain/awm217

DO - 10.1093/brain/awm217

M3 - Article

C2 - 17893097

AN - SCOPUS:35648963039

VL - 130

SP - 2858

EP - 2867

JO - Brain

JF - Brain

SN - 0006-8950

IS - 11

ER -