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The role of the amygdala during emotional processing in Huntington's disease : from pre-manifest to late stage disease

Mason, Sarah L; Zhang, Jiaxiang; Begeti, Faye; Guzman, Natalie Valle; Lazar, Alpar S; Rowe, James B; Barker, Roger A LU and Hampshire, Adam (2015) In Neuropsychologia 70. p.9-80
Abstract

BACKGROUND: Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis.

METHODS: We investigated... (More)

BACKGROUND: Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis.

METHODS: We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: "the Reading the Mind in the Eyes Test" which has been previously been shown to be amygdala dependent.

RESULTS: Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, p<0.05). Furthermore, performance on the "Reading the Mind in the Eyes Test" correlated negatively with proximity to disease onset and became progressively worse with each stage of disease.

CONCLUSION: Abnormalities in the neural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntington's disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis. Furthermore, the "Reading the Mind in the Eyes Test" is a surrogate measure of amygdala function that is clinically useful across the entire cross-section of disease stages in HD.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Age of Onset, Amygdala, Asymptomatic Diseases, Brain Mapping, Cognition, Emotions, Facial Expression, Female, Humans, Huntington Disease, Image Processing, Computer-Assisted, Male, Mental Status Schedule, Middle Aged, Neural Pathways, Neuropsychological Tests, Oxygen, Photic Stimulation, Reaction Time, Theory of Mind, Journal Article, Research Support, Non-U.S. Gov't
in
Neuropsychologia
volume
70
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:84925770609
ISSN
1873-3514
DOI
10.1016/j.neuropsychologia.2015.02.017
language
English
LU publication?
no
id
77d7a185-c4c4-492a-bdae-323feab3a66f
date added to LUP
2016-11-24 14:54:54
date last changed
2017-09-17 09:33:03
@article{77d7a185-c4c4-492a-bdae-323feab3a66f,
  abstract     = {<p>BACKGROUND: Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis.</p><p>METHODS: We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: "the Reading the Mind in the Eyes Test" which has been previously been shown to be amygdala dependent.</p><p>RESULTS: Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, p&lt;0.05). Furthermore, performance on the "Reading the Mind in the Eyes Test" correlated negatively with proximity to disease onset and became progressively worse with each stage of disease.</p><p>CONCLUSION: Abnormalities in the neural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntington's disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis. Furthermore, the "Reading the Mind in the Eyes Test" is a surrogate measure of amygdala function that is clinically useful across the entire cross-section of disease stages in HD.</p>},
  author       = {Mason, Sarah L and Zhang, Jiaxiang and Begeti, Faye and Guzman, Natalie Valle and Lazar, Alpar S and Rowe, James B and Barker, Roger A and Hampshire, Adam},
  issn         = {1873-3514},
  keyword      = {Adult,Age of Onset,Amygdala,Asymptomatic Diseases,Brain Mapping,Cognition,Emotions,Facial Expression,Female,Humans,Huntington Disease,Image Processing, Computer-Assisted,Male,Mental Status Schedule,Middle Aged,Neural Pathways,Neuropsychological Tests,Oxygen,Photic Stimulation,Reaction Time,Theory of Mind,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  pages        = {9--80},
  publisher    = {Elsevier},
  series       = {Neuropsychologia},
  title        = {The role of the amygdala during emotional processing in Huntington's disease : from pre-manifest to late stage disease},
  url          = {http://dx.doi.org/10.1016/j.neuropsychologia.2015.02.017},
  volume       = {70},
  year         = {2015},
}