A theoretical analysis of the role of hyperarousal in the learning and behavior of fragile X males
Mental Retardation and Developmental Disabilities Research ReviewsPublished 1 January 1995
Ira L. Cohen
Citations88
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Clinical data suggest fragile X males have problems with arousal modulation, and it is hypothesized that these arousal problems have an impact on both the acquisition and display of cognitive and adaptive skills.
Abstract
Abstract Fragile X syndrome, the most common form of inherited mental retardation, is associated with a broad spectrum of cognitive and behavioral impairments. Researchers have noted a characteristic behavioral profile consisting of social avoidance, as well as verbal and motor repetitive behaviors, in a subgroup of males with fragile X syndrome. Although these behaviors are evident in their most extreme form in males having both fragile X syndrome and autism, milder variants are evident in nonautistic males as well. Clinical data we have collected suggest that the severity of these agitated behaviors starts increasing during adolescence. These data suggest fragile X males have problems with arousal modulation. It is hypothesized that these arousal problems have an impact on both the acquisition and display of cognitive and adaptive skills. Neurocomputational issues that may be relevant to understanding these cognitive and emotional phenomena are discussed. © 1995 Wiley‐Liss, Inc.
Keywords
Social SciencesNeuroscienceBiochemistry, Genetics and Molecular Biology
Journal of Comparative Neurology and PsychologyThe relation of strength of stimulus to rapidity of habit‐formation
6,795 Citations1908Robert M. Yerkes, John Dodson
CellIdentification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
3,507 Citations1991Annemieke J.M.H. Verkerk, Maura Pieretti +19 more
A fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes is identified and localization of the brain-expressed FMR-1 gene to this EcoRI fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome.
Computer Vision Graphics and Image ProcessingA massively parallel architecture for a self-organizing neural pattern recognition machine
2,519 Citations1987Gail A. Carpenter, Stephen Grossberg
A neural network architecture for the learning of recognition categories is derived which circumvents the noise, saturation, capacity, orthogonality, and linear predictability constraints that limit the codes which can be stably learned by alternative recognition models.
Electroencephalography and Clinical NeurophysiologyCyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming
1,863 Citations1957William C. Dement, Nathaniel Kleitman
Records from a large number of nights in single individuals indicated that some could maintain a very striking regularity in their sleep pattern from night to night, and that body movement, after rising to a peak, dropped sharply at the onset of rapid eye movements and rebounded abruptly as the eye movements ceased.
ScienceInstability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome
1,492 Citations1991I. Oberlé, F. Rousseau +7 more
expression of the fragile X syndrome appears to result from a two-step mutation as well as a highly localized methylation, and can easily be detected regardless of sex or phenotypic expression.
CellAbsence of expression of the FMR-1 gene in fragile X syndrome
1,482 Citations1991Maura Pieretti, Fuping Zhang +5 more
FMR-1 mRNA was absent in the majority of male fragile X patients, suggesting a close involvement of this gene in development of the syndrome, and the methylation status of the BssHII site at the CpG island was studied.
ScienceMapping of DNA Instability at the Fragile X to a Trinucleotide Repeat Sequence P(CCG) <i>n</i>
923 Citations1991Eric J. Kremer, Melanie Pritchard +8 more
Physiology & BehaviorThe nature and determinants of adjunctive behavior
812 Citations1971John L. Falk
The similarities among the various behaviors induced as adjuncts to the behaviors under direct schedule control are described in terms of their intensities, temporal loci, and the variables which produce them.
ScienceFragile X Genotype Characterized by an Unstable Region of DNA
799 Citations1991Shuancang Yu, Melanie Pritchard +10 more
This probe provides a means with which to analyze fragile X pedigrees and is a diagnostic reagent for the fragile X genotype.
Social Psychiatry and Psychiatric EpidemiologyEpidemiology of autistic conditions in young children
764 Citations1966Victor Lotter
It is pointed out that sub-division according to the presence of developmental retardation is necessary for the useful comparison of reported groups, particularly with respect to estimates of prognosis, and the relationship between early development, type of onset and I.Q.
American Journal of Medical GeneticsAnalysis of neocortex in three males with the fragile X syndrome
509 Citations1991Veronica J. Hinton, W. Ted Brown +2 more
Nature GeneticsTissue specific expression of FMR–1 provides evidence for a functional role in fragile X syndrome
395 Citations1993Heather L. Hinds, Claude T. Ashley +5 more
The early embryonic onset and tissue specificity of FMR–1 gene expression is consistent with involvement in the fragile X phenotype, and also suggests additional organ systems in which clinical manifestations of reduced FMR-1 gene Expression may occur.
Nature GeneticsNucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain
281 Citations1993Marc Abitbol, Christian Ménini +4 more
The early transcription of F MR–1 gene and the distribution of FMR–1 mRNAs in human fetuses suggest that alterations of FMSG gene expression may contribute to the pathogenesis of fragile–X syndrome and especially the mental retardation.
Nature MedicineNeurodevelopmental effects of the FMR-1 full mutation in humans
239 Citations1995Allan L. Reiss, Michael T. Abrams +3 more
It is suggested that the FMR-1 mutation causing the fragile X syndrome leads to observable changes in neuroanatomy that may be relevant to the neurodevelopmental disability and behavioural problems observed in affected individuals.
The NeuroscientistREVIEW ■ : Toward a Neurobiology of Emotion and Feeling: Operational Concepts and Hypotheses
215 Citations1995António R. Damásio
Elsevier eBooksTHE AMYGDALA: SENSORY GATEWAY TO THE EMOTIONS
197 Citations1986John P. Aggleton, Mortimer Mishkin
The anatomical evidence strongly reinforces the view derived from neurobehavioral studies that the striking lack of emotional behavior following amygdalectomy is the consequence of a disconnection of cortically processed sensory information from affective mechanisms centered in the hypothalamus and midbrain.
American Journal of Medical GeneticsCognitive profiles associated with the fra(X) syndrome in males and females
186 Citations1991Lisa S. Freund, Allan L. Reiss
Cognitive profiles generated from the Stanford-Binet Intelligence Scale indicated a pattern of subtest strengths and weaknesses that was similar for both groups, and specific, S-B-identified cognitive weaknesses associated with the fra(X) condition are potentially useful indicators for investigation of specific cognitive process deficits.
NeurologyNeuroanatomy of fragile X syndrome
185 Citations1994Allan L. Reiss, James Lee +1 more
The results of the present investigation are consistent with studies showing a nonrandom distribution of expression of the FMR-1 gene in the developing brain, with increased expression in the cerebellum, hippocampus, and specific cortical regions, and suggest involvement of temporal lobe regions in the behavioral and cognitive abnormalities associated with fragile X syndrome.
PsychobiologyNeural dynamics of attentionally modulated Pavlovian conditioning: Conditioned reinforcement, inhibition, and opponent processing
181 Citations1987Stephen Grossberg, Néstor A. Schmajuk
A real-time neural network model is developed to explain data about the acquisition and extinction of conditioned excitors and inhibitors, and clarifies why alternative models have been unable to explain an equally large data base.
Annals of NeurologyNeuroanatomy of fragile X syndrome: The posterior fossa
171 Citations1991Allan L. Reiss, Elizabeth Aylward +3 more
The size of the posterior cerebellar vermis was significantly decreased and the fourth ventricle significantly increased in the group of males with fragile X syndrome compared with males in both comparison groups, and neuroanatomical abnormalities appeared to be secondary to hypoplasia rather than atrophy.
PubMedConversational analyses of males with fragile X, Down syndrome, and autism: comparison of the emergence of deviant language.
157 Citations1990Vicki Sudhalter, I L Cohen +2 more
The deviant repetitive language of males with fra(X) cannot be accounted for by either their level of adaptive functioning or autistic-like behaviors per se, and possible explanations for this etiologically specific language deviance were discussed.
Journal of Autism and Developmental DisordersFragile X syndrome: genetic predisposition to psychopathology
154 Citations1988Joel D. Bregman, James F. Leckman +1 more
Pervasive hyperactivity, impulsivity, and attentional deficits were found among all of the subjects, while a significant degree of anxiety was manifested by more than half, and gaze aversion was attributed to underlying anxiety rather than to autistic social dysfunction because of the otherwise socially engaged and affectionate behavior exhibited by the subjects.
PubMedSocial gaze, social avoidance, and repetitive behavior in fragile X males: a controlled study.
140 Citations1988Cohen Il, GS Fisch +6 more
Preference for social gaze as well as the percentage occurrence of social gaze, nonverbal social avoidance, and nonverbal repetitive behaviors were examined in autistic and nonautistic prepubertal males with the fragile X syndrome during social interaction with a parent or stranger.
Biological PsychiatryAn artificial neural network analogue of learning in autism
123 Citations1994Ira L. Cohen
It is concluded that the neuropathological observations that have been described in the literature are sufficient to explain some of the unique pattern recognition and discrimination learning abilities seen in some people with autism as well as their problems with generalization and concept acquisition.
PubMedWhy are autism and the fragile-X syndrome associated? Conceptual and methodological issues.
119 Citations1991Ira L. Cohen, Vicki Sudhalter +4 more
It is concluded that autism and fragile X are associated and that this relation will prove fruitful in understanding the role of the X chromosome in a variety of behavior disorders and in unraveling various theoretical accounts on the etiology of autism.
Journal of Autism and Developmental DisordersThe prevalence of autism in Nagoya, Japan: A total population study
111 Citations1989Toshiro Sugiyama, Tokuichiro Abe
The authors have been involved in routine well-child medical examinations at 18 months of age, at the Midori Public Health Center in Nagoya, for the purpose of conducting an epidemiological study of autism.
Journal of Child Psychology and PsychiatryParent‐Child Dyadic Gaze Patterns in Fragile X Males and in Non‐fragile X Males with Autistic Disorder
108 Citations1989Ira L. Cohen, Peter M. Vietze +3 more
Event lag sequential analyses indicated that fra(X) males were sensitive to social gaze initiation by their parents but found eye contact aversive, and non-fra( X) autistic males, by contrast, were insensitive to parent-initiated social gaze, and did not find eye Contact aversive.
Journal of the American Academy of Child & Adolescent PsychiatryThe Trajectory of Cognitive Development in Males with Fragile X Syndrome
106 Citations1989Elisabeth M. Dykens, Robert M. Hodapp +4 more
Parents and teachers should be informed about the possibility of an early plateau in mental age, the impact this may have on the child's academic performance, and that the plateau and IQ decline may not be apparent in the child’s adaptive behaviors.
Elsevier eBooksNEURAL SYSTEMS INVOLVED IN EMOTION IN PRIMATES
93 Citations1986Edmund T. Rolls
The amygdala and orbitofrontal cortex are seen to be of great importance for emotions, in that they are involved respectively in the elicitation of learned emotional responses and in the correction or adjustment of these emotional responses as the reinforcing values of environmental stimuli alter.
American Journal of Medical GeneticsLongitudinal IQ changes in fragile X males
90 Citations1989Randi J. Hagerman, Rebecca Schreiner +4 more
Visual inspection demonstrates an initial decline in IQ beginning in middle childhood and continuing through adolescence, and it is postulate that this drop occurs because of relatively greater weaknesses with abstract reasoning and higher symbolic language skills that are stressed in the cognitive testing of later childhood and adolescence.
PubMedDeclining IQs of young males with the fragile X syndrome.
86 Citations1987A M Lachiewicz, Christina M. Gullion +2 more
Retrospective, longitudinal data were obtained on 21 boys with the fragile X syndrome to assess whether their IQs declined during childhood; for the group as a whole, IQs dropped significantly; 13 boys showed a significant decline at retest.
Journal of the American Academy of Child & Adolescent PsychiatryDevelopmental Implications of Changing Trajectories of IQ in Males with Fragile X Syndrome
84 Citations1990Robert M. Hodapp, Elisabeth M. Dykens +4 more
It is demonstrated that males with fragile X syndrome show a decline in IQ scores, with the most marked declines seen during the early pubertal period, suggesting a slowing of development associated with the onset of puberty.
American Journal of Medical GeneticsSyntactic delay and pragmatic deviance in the language of fragile X males
83 Citations1991Vicki Sudhalter, Hollis S. Scarborough +1 more
The expressive language of 19 fragile X [fra(X)] males with chronological ages between 5 and 36 years and Vineland Adaptive Behavior Scores between 21 and 79 was examined for syntactic as well as pragmatic proficiency and the relation of complexity to length was observed to be very similar to the known relationship of these 2 facets of syntactic ability in normal preschoolers.
Archives of Pediatrics and Adolescent MedicineLearning Disabilities and Attentional Problems in Boys With the Fragile X Syndrome
83 Citations1985Randi J. Hagerman
All four patients demonstrated similar learning difficulties that included hyperactivity, visuomotor incoordination, language deficits, and academic delays in mathematics, and the IQ scores of these patients extended into the normal range.
American Journal of Medical GeneticsEffects of age and communication level on eye contact in fragile X males and non‐fragile X autistic males
77 Citations1991Ira L. Cohen, Peter M. Vietze +3 more
PubMedAberrant behaviors of young boys with fragile X syndrome.
73 Citations1994Lachiewicz Am, Spiridigliozzi Ga +3 more
Boys with fragile X were found times more likely to have both tactile defensiveness and abnormal language, and the presence of these abnormal behaviors in boys with developmental delays warrants further assessment for fragile X.
Journal of Autism and Developmental DisordersTrajectory of adaptive behavior in males with fragile X syndrome
65 Citations1993Elisabeth M. Dykens, Robert M. Hodapp +2 more
There was a significant relationship between adaptive behavior and mental age scores in all subjects, and a relative strength in Daily Living Skills and weakness in Socialization emerged only among older subjects.
American Journal of Medical GeneticsExpressive semantic deficit in the productive language of males with fragile X syndrome
56 Citations1992Vicki Sudhalter, Maria Maranion +1 more
It was shown that sentences which could be correctly completed by a wider choice of words affected fra(X) males more than the nondisabled children.
Journal of Autism and Developmental DisordersA neural network approach to the classification of autism
44 Citations1993Ira L. Cohen, Vicki Sudhalter +2 more
The neural network methodology was superior to discriminant function analysis both in its ability to classify groups and to generalize to new cases that were not part of the training sample and for understanding of possible core deficits in autism.
Elsevier eBooksAMYGDALA, EMOTIONS, MOTIVATION, AND DEPRESSIVE STATES
34 Citations1986Elżbieta Fonberg
It is concluded that experiments on animals give exciting perspectives for investigations of amygdalar mechanisms in humans and may be useful for treatment of emotional disorders, depression, and neuroses.