Auditory and visual cortical activity during selective attention in fragile X syndrome: A cascade of processing deficiencies

Molen, Melle J. W. van der; Molen, Maurits W. van der; Ridderinkhof, K.R.; Hamel, B.C.J.; Curfs, L.M.G.; Ramakers, G.J.A.

doi:10.1016/j.clinph.2011.08.023

Cited by 80 publications

(141 citation statements)

References 60 publications

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“…Electrophysiological studies also indicate that children with ADHD differ from controls at multiple time points in the information processing cascade leading to the inhibition of a response or when resolving conflict (Liotti, Pliszka, Perez, Kothmann, & Woldorff, 2005). Again, very similar findings have emerged from electrophysiological studies of adolescents and adults with FXS (van der Molen et al, 2012).…”

Section: Relationships To the Principles Of Developmental Psychopathosupporting

confidence: 60%

“…Are these unimpaired in FXS? Studies with adults (Van der Molen et al, 2012) and also with infants with FXS (Farzin, Whitney, Hagerman, & Rivera, 2008) suggest that visuospatial attention impairments may in fact be underpinned by atypical lower level perceptual abilities. Again, longitudinal data are crucial in evaluating whether low-level perceptual processing differences do in fact lead over developmental time to atypical higher level processing.…”

Section: Insights From Longitudinal Studies Of Fragile Xmentioning

confidence: 99%

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Fragile X Syndrome as a Multilevel Model for Understanding Behaviorally Defined Disorders

Karmiloff‐Smith

Doherty

Cornish

et al. 2016

Developmental Psychopathology

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Because of the growing availability and feasibility of genetic testing, neurodevelopmental disorders of identified genetic etiology (i.e., genetic disorders) are increasingly diagnosed in early childhood, perinatally or even prenatally. Multiple genetic disorders are also associated with high risk for a diverse range of childhood psychopathological outcomes, such as attention‐deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Genetic disorders therefore offer an appealing opportunity: mapping between genetic differences, atypical brain function, cognitive development, and risk for psychopathological outcomes. Here we focus on a specific monogenic disorder, fragile X syndrome (FXS), to illustrate the complexities of mapping efforts across levels of description, and the need for a developmental perspective throughout. In applied terms, the comparison between FXS and other genetic disorders at high risk also pinpoints subtly diverging profiles of risk and thus the need for information about differences in early neurocognitive trajectories, to optimize early intervention in a syndrome‐specific way. Understanding neurodevelopmental trajectories to both poor and good outcomes across multiple genetic disorders will require increasing collaborations between basic and clinical neuroscientists, with mechanisms of typical and atypical neurocognitive development clearly in focus.

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Section: Relationships To the Principles Of Developmental Psychopathosupporting

confidence: 60%

Section: Insights From Longitudinal Studies Of Fragile Xmentioning

confidence: 99%

Fragile X Syndrome as a Multilevel Model for Understanding Behaviorally Defined Disorders

Karmiloff‐Smith

Doherty

Cornish

et al. 2016

Developmental Psychopathology

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“…Behavioral and functional studies indicate abnormal auditory sensitivity in humans with FXS (St Clair et al, 1987; Castren et al, 2003; Van der Molen et al, 2012a,b; Schneider et al, 2013; Rotschafer and Razak, 2014). A consistent observation in FXS is that the amplitude of the N1 component of auditory event related potentials (ERP) shows reduced habituation with sound repetition compared to the control group, suggesting neural correlates of auditory hypersensitivity.…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome

Lovelace

Wen

Reinhard

et al. 2016

Neurobiology of Disease

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Sensory processing deficits are common in autism spectrum disorders, but the underlying mechanisms are unclear. Fragile X Syndrome (FXS) is a leading genetic cause of intellectual disability and autism. Electrophysiological responses in humans with FXS show reduced habituation with sound repetition and this deficit may underlie auditory hypersensitivity in FXS. Our previous study in Fmr1 knockout (KO) mice revealed an unusually long state of increased sound-driven excitability in auditory cortical neurons suggesting that cortical responses to repeated sounds may exhibit abnormal habituation as in humans with FXS. Here, we tested this prediction by comparing cortical event related potentials (ERP) recorded from wildtype (WT) and Fmr1 KO mice. We report a repetition-rate dependent reduction in habituation of N1 amplitude in Fmr1 KO mice and show that matrix metalloproteinase −9 (MMP-9), one of the known FMRP targets, contributes to the reduced ERP habituation. Our studies demonstrate a significant up-regulation of MMP-9 levels in the auditory cortex of adult Fmr1 KO mice, whereas a genetic deletion of Mmp-9 reverses ERP habituation deficits in Fmr1 KO mice. Although the N1 amplitude of Mmp-9/Fmr1 DKO recordings was larger than WT and KO recordings, the habituation of ERPs in Mmp-9/Fmr1 DKO mice is similar to WT mice implicating MMP-9 as a potential target for reversing sensory processing deficits in FXS. Together these data establish ERP habituation as a translation relevant, physiological pre-clinical marker of auditory processing deficits in FXS and suggest that abnormal MMP-9 regulation is a mechanism underlying auditory hypersensitivity in FXS.

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“…The percentage of FMRP is critical during neurodevelopment, as it is involved in regulating synaptic plasticity and dendritic pruning (Harlow et al, 2010). Reduced levels (or percentage) of FMRP has been associated with intellectual disability (Reiss and Dant, 2003), cognitive and behavioral impairments (Van der Molen et al, 2012), and high prevalence of autism symptomatology (Gabis et al, 2011). Further, FXS is linked with altered structural and functional brain connectivity (Haas et al, 2009; Hall et al, 2013; Wang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Estimating individual contribution from group-based structural correlation networks

et al. 2015

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Coordinated variations in brain morphology (e.g., cortical thickness) across individuals have been widely used to infer large-scale population brain networks. These structural correlation networks (SCNs) have been shown to reflect synchronized maturational changes in connected brain regions. Further, evidence suggests that SCNs, to some extent, reflect both anatomical and functional connectivity and hence provide a complementary measure of brain connectivity in addition to diffusion weighted networks and resting-state functional networks. Although widely used to study between-group differences in network properties, SCNs are inferred only at the group-level using brain morphology data from a set of participants, thereby not providing any knowledge regarding how the observed differences in SCNs are associated with individual behavioral, cognitive and disorder states. In the present study, we introduce two novel distance-based approaches to extract information regarding individual differences from the group-level SCNs. We applied the proposed approaches to a moderately large dataset (n=100) consisting of individuals with fragile X syndrome (FXS; n=50) and age-matched typically developing individuals (TD; n=50). Additionally, we tested the stability of proposed approaches using permutation analysis. Lastly, to test the efficacy of our method, individual contributions extracted from the group-level SCNs were examined for associations with intelligence scores and genetic data. The extracted individual contributions were stable and were significantly related to both genetic and intelligence estimates, in both typically developing individuals and participants with FXS. We anticipate that the approaches developed in this work could be used as a putative biomarker for altered connectivity in individuals with neurodevelopmental disorders.

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Auditory and visual cortical activity during selective attention in fragile X syndrome: A cascade of processing deficiencies

Cited by 80 publications

References 60 publications

Fragile X Syndrome as a Multilevel Model for Understanding Behaviorally Defined Disorders

Fragile X Syndrome as a Multilevel Model for Understanding Behaviorally Defined Disorders

Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome

Estimating individual contribution from group-based structural correlation networks

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