Altered neural activity of magnitude estimation processing in adults with the fragile X premutation

So Yeon Kim, Ryu ichiro Hashimoto, Flora Tassone, Tony J Simon, Susan M. Rivera

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Mutations of the fragile X mental retardation 1 ( FMR1) gene are the genetic cause of fragile X syndrome (FXS). Expanded CGG trinucleotide repeat (>200 repeats) result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA, and are associated with the risk of developing a neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). While impairments in numerical processing have been well documented in FXS, recent behavioral research suggests that premutation carriers also present with subtle but significant impairments in numerical processing. Using fMRI, the current study examined whether asymptomatic adults with the premutation would show aberrant neural correlates of magnitude estimation processing in the fronto-parietal area. Using a magnitude estimation task, we demonstrated that activity in the intraparietal sulcus and inferior frontal gyrus, associated with magnitude estimation processing, was significantly attenuated in premutation carriers compared to their neurotypical counterparts despite their comparable behavioral performance. Further, multiple regression analysis using CGG repeat size and FMR1 mRNA indicated that increased CGG repeat size is a primary factor for the decreased fronto-parietal activity, suggesting that reduced FMRP, rather than a toxic gain-of-function effect from elevated mRNA, contributes to altered neural activity of magnitude estimation processing in premutation carriers. In conclusion, we provide the first evidence on the aberrant neural correlates of magnitude estimation processing in premutation carriers accounted for by their FMR1 gene expression.

Original languageEnglish (US)
Pages (from-to)1909-1916
Number of pages8
JournalJournal of Psychiatric Research
Volume47
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Intellectual Disability
Fragile X Syndrome
Messenger RNA
Fragile X Mental Retardation Protein
Trinucleotide Repeat Expansion
Behavioral Research
Parietal Lobe
Poisons
Prefrontal Cortex
Neurodegenerative Diseases
Genes
Proteins
Alleles
Regression Analysis
Magnetic Resonance Imaging
Mental Retardation
Magnitude Estimation
Gene Expression
Mutation
Carrier

Keywords

  • FMR1 gene
  • Fragile X premutation
  • Frontal and parietal areas
  • Functional MRI
  • Magnitude estimation processing
  • Perception

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Arts and Humanities (miscellaneous)

Cite this

Altered neural activity of magnitude estimation processing in adults with the fragile X premutation. / Kim, So Yeon; Hashimoto, Ryu ichiro; Tassone, Flora; Simon, Tony J; Rivera, Susan M.

In: Journal of Psychiatric Research, Vol. 47, No. 12, 12.2013, p. 1909-1916.

Research output: Contribution to journalArticle

@article{83654c38e3d143d5adeb23aa00041602,
title = "Altered neural activity of magnitude estimation processing in adults with the fragile X premutation",
abstract = "Mutations of the fragile X mental retardation 1 ( FMR1) gene are the genetic cause of fragile X syndrome (FXS). Expanded CGG trinucleotide repeat (>200 repeats) result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA, and are associated with the risk of developing a neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). While impairments in numerical processing have been well documented in FXS, recent behavioral research suggests that premutation carriers also present with subtle but significant impairments in numerical processing. Using fMRI, the current study examined whether asymptomatic adults with the premutation would show aberrant neural correlates of magnitude estimation processing in the fronto-parietal area. Using a magnitude estimation task, we demonstrated that activity in the intraparietal sulcus and inferior frontal gyrus, associated with magnitude estimation processing, was significantly attenuated in premutation carriers compared to their neurotypical counterparts despite their comparable behavioral performance. Further, multiple regression analysis using CGG repeat size and FMR1 mRNA indicated that increased CGG repeat size is a primary factor for the decreased fronto-parietal activity, suggesting that reduced FMRP, rather than a toxic gain-of-function effect from elevated mRNA, contributes to altered neural activity of magnitude estimation processing in premutation carriers. In conclusion, we provide the first evidence on the aberrant neural correlates of magnitude estimation processing in premutation carriers accounted for by their FMR1 gene expression.",
keywords = "FMR1 gene, Fragile X premutation, Frontal and parietal areas, Functional MRI, Magnitude estimation processing, Perception",
author = "Kim, {So Yeon} and Hashimoto, {Ryu ichiro} and Flora Tassone and Simon, {Tony J} and Rivera, {Susan M.}",
year = "2013",
month = "12",
doi = "10.1016/j.jpsychires.2013.08.014",
language = "English (US)",
volume = "47",
pages = "1909--1916",
journal = "Journal of Psychiatric Research",
issn = "0022-3956",
publisher = "Elsevier Limited",
number = "12",

}

TY - JOUR

T1 - Altered neural activity of magnitude estimation processing in adults with the fragile X premutation

AU - Kim, So Yeon

AU - Hashimoto, Ryu ichiro

AU - Tassone, Flora

AU - Simon, Tony J

AU - Rivera, Susan M.

PY - 2013/12

Y1 - 2013/12

N2 - Mutations of the fragile X mental retardation 1 ( FMR1) gene are the genetic cause of fragile X syndrome (FXS). Expanded CGG trinucleotide repeat (>200 repeats) result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA, and are associated with the risk of developing a neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). While impairments in numerical processing have been well documented in FXS, recent behavioral research suggests that premutation carriers also present with subtle but significant impairments in numerical processing. Using fMRI, the current study examined whether asymptomatic adults with the premutation would show aberrant neural correlates of magnitude estimation processing in the fronto-parietal area. Using a magnitude estimation task, we demonstrated that activity in the intraparietal sulcus and inferior frontal gyrus, associated with magnitude estimation processing, was significantly attenuated in premutation carriers compared to their neurotypical counterparts despite their comparable behavioral performance. Further, multiple regression analysis using CGG repeat size and FMR1 mRNA indicated that increased CGG repeat size is a primary factor for the decreased fronto-parietal activity, suggesting that reduced FMRP, rather than a toxic gain-of-function effect from elevated mRNA, contributes to altered neural activity of magnitude estimation processing in premutation carriers. In conclusion, we provide the first evidence on the aberrant neural correlates of magnitude estimation processing in premutation carriers accounted for by their FMR1 gene expression.

AB - Mutations of the fragile X mental retardation 1 ( FMR1) gene are the genetic cause of fragile X syndrome (FXS). Expanded CGG trinucleotide repeat (>200 repeats) result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA, and are associated with the risk of developing a neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). While impairments in numerical processing have been well documented in FXS, recent behavioral research suggests that premutation carriers also present with subtle but significant impairments in numerical processing. Using fMRI, the current study examined whether asymptomatic adults with the premutation would show aberrant neural correlates of magnitude estimation processing in the fronto-parietal area. Using a magnitude estimation task, we demonstrated that activity in the intraparietal sulcus and inferior frontal gyrus, associated with magnitude estimation processing, was significantly attenuated in premutation carriers compared to their neurotypical counterparts despite their comparable behavioral performance. Further, multiple regression analysis using CGG repeat size and FMR1 mRNA indicated that increased CGG repeat size is a primary factor for the decreased fronto-parietal activity, suggesting that reduced FMRP, rather than a toxic gain-of-function effect from elevated mRNA, contributes to altered neural activity of magnitude estimation processing in premutation carriers. In conclusion, we provide the first evidence on the aberrant neural correlates of magnitude estimation processing in premutation carriers accounted for by their FMR1 gene expression.

KW - FMR1 gene

KW - Fragile X premutation

KW - Frontal and parietal areas

KW - Functional MRI

KW - Magnitude estimation processing

KW - Perception

UR - http://www.scopus.com/inward/record.url?scp=84886092257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886092257&partnerID=8YFLogxK

U2 - 10.1016/j.jpsychires.2013.08.014

DO - 10.1016/j.jpsychires.2013.08.014

M3 - Article

C2 - 24045061

AN - SCOPUS:84886092257

VL - 47

SP - 1909

EP - 1916

JO - Journal of Psychiatric Research

JF - Journal of Psychiatric Research

SN - 0022-3956

IS - 12

ER -