Attention and language in fragile X

Abstract

Fragile X syndrome (FXS) is a well-recognized cause of mental retardation and developmental delay in males. Alongside the well-documented clinical characteristics of the condition, recent advances in technology and methodology have begun to define FXS at a number of different levels: genetic, brain structure and function, cognition, and behavior. This article suggests that the FXS phenotype is not merely a juxtaposition of spared and impaired functions but rather may be characterized by an inhibitory control deficit that interferes with the individual's ability to modulate output causing perseverative responding across various skill areas. It is further suggested that an inability to modulate arousal may be at least one cause for the inhibitory control deficit that typifies the FXS phenotype. The approach to understanding atypical development outlined here holds exciting promise for future research in FXS and other developmental disorders.

Mental retardation genes in drosophila: New approaches to understanding and treating developmental brain disorders

“…FXS patients have loss-of-function mutations of Fmr1, which causes a distinctive profile of cognitive deficits of varying severity, along with enlarged testes, characteristic facies, and, in some patients, other neurological features such as autism, epilepsy, and disordered sleep [Hagerman, 2002;Cornish et al, 2004]. Evidence from both mammalian and fly systems strongly supports a working model in which FMRP's primary neuronal function is selective RNA binding and transport to dendrites, for the purpose of translational controlmainly repression-of specific proteins in a synaptic activity-dependent manner [Darnell et al, 2004;Willemsen et al, 2004].…”

“…This inability to suppress a behavior might also represent a form of perseveration. Short-term memory for complex tasks is one of the specific weaknesses of the human FXS cognitive profile [Cornish et al, 2004]. In addition, lack of behavioral inhibition, which often results in perseveration, has been proposed as a fundamental underlying deficit in FXS [Cornish et al, 2004].…”

“…Short-term memory for complex tasks is one of the specific weaknesses of the human FXS cognitive profile [Cornish et al, 2004]. In addition, lack of behavioral inhibition, which often results in perseveration, has been proposed as a fundamental underlying deficit in FXS [Cornish et al, 2004]. Because dfmr1 mutant performance on other tasks has not yet been reported, it is too early to conclude anything about the scope and specificity of the cognitive deficit.…”

“…Behavioral phenotypes are more difficult to compare. Is the reduced courtship interest of dfmr1 mutant males [Dockendorff et al, 2002] a reflection of reduced libido or is it a counterpart of social anxiety and avoidance seen in FXS males [Cornish et al, 2004]? For now, I would argue that the phenotypic details may matter less than the molecular pathways underlying them, for, if mechanisms are similar, then drug-based treatments should be similar as well.…”

Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome

“…In humans, attention-distracting stimuli interfere with trace but not delay conditioning (Clark and Squire, 1998;Manns et al, 2000). Because many children with fragile X are diagnosed with attention deficit/hyperactivity disorder (ADHD) (Hagerman et al, 1996;Cornish et al, 2004), we hypothesized that this form of associative learning may be disrupted in FMR1 KO mice and alterations in synaptic plasticity within the ACC may underlie any observed deficits.…”