scholarly journals What can developmental disorders tell us about the neurocomputational constraints that shape development? The case of Williams syndrome

2003 ◽  
Vol 15 (4) ◽  
pp. 969-990 ◽  
Author(s):  
ANNETTE KARMILOFF–SMITH ◽  
MICHAEL THOMAS
Keyword(s):  
Williams Syndrome ◽  
Developmental Disorders ◽  
Genetic Disorders ◽  
Actual Process ◽  
Cognitive Domains ◽  
Behavioral Studies ◽  
Starting Point ◽  
Cognitive Modularity ◽  
Genetically Determined ◽  
The Brain

The uneven cognitive phenotype in the adult outcome of Williams syndrome has led some researchers to make strong claims about the modularity of the brain and the purported genetically determined, innate specification of cognitive modules. Such arguments have particularly been marshaled with respect to language. We challenge this direct generalization from adult phenotypic outcomes to genetic specification and consider instead how genetic disorders provide clues to the constraints on plasticity that shape the outcome of development. We specifically examine behavioral studies, brain imaging, and computational modeling of language in Williams syndrome but contend that our theoretical arguments apply equally to other cognitive domains and other developmental disorders. While acknowledging that selective deficits in normal adult patients might justify claims about cognitive modularity, we question whether similar, seemingly selective deficits found in genetic disorders can be used to argue that such cognitive modules are prespecified in infant brains. Cognitive modules are, in our view, the outcome of development, not its starting point. We note that most work on genetic disorders ignores one vital factor, the actual process of ontogenetic development, and argue that it is vital to view genetic disorders as proceeding under different neurocomputational constraints, not as demonstrations of static modularity.

LANGUAGE AND WILLIAMS SYNDROME

2008 ◽  
Vol 28 ◽  
pp. 191-204 ◽  
Author(s):  
Ching-fen Hsu ◽  
Annette Karmiloff-Smith
Keyword(s):  
Williams Syndrome ◽  
Cognitive Processes ◽  
Language Production ◽  
Developmental Disorders ◽  
Human Life ◽  
Initial State ◽  
Functional Brain ◽  
Functional Brain Networks ◽  
Overt Language Production ◽  
The Brain

Most aspects of human life—from gene expression, to brain structure/function, to underlying linguistic and cognitive processes, through to overt language production and comprehension behaviors—are the result of dynamic developmental processes, in which timing plays a crucial role. So, the study of language acquisition in developmental disorders such as Williams syndrome (WS) needs to change from the still widely held view that developmental disorders can be accounted for in terms of spared versus impaired modules to one that takes serious account of the fact that the infant cortex passes from an initial state of high regional interconnectivity to a subsequent state of progressively increasing specialization and localization of functional brain networks. With such early interconnectivity in mind, developmental neuroscientists must explore the possibility that a small perturbation in low-level processes in one part of the brain very early in development can result in serious deficits in higher-level processes in another part of the brain later in development. Therefore, in profiling developmental disorders of language such as in WS, it is vital to start in early infancy, from which to trace the full trajectory of the interactions of language and other cognitive processes across infancy, toddlerhood, and childhood, through to adolescence and adulthood.

I. The Neurocognitive Profile of Williams Syndrome: A Complex Pattern of Strengths and Weaknesses

2000 ◽  
Vol 12 (supplement 1) ◽  
pp. 7-29 ◽  
Author(s):  
Ursula Bellugi ◽  
Liz Lichtenberger ◽  
Wendy Jones ◽  
Zona Lai ◽  
Marie St. George
Keyword(s):  
Williams Syndrome ◽  
Cognitive Abilities ◽  
Interdisciplinary Research ◽  
Genetic Basis ◽  
Cognitive Profile ◽  
Cognitive Domains ◽  
Cognitive Characteristics ◽  
Neurocognitive Profile ◽  
Moderate Range ◽  
The Brain

The rare, genetically based disorder, Williams syndrome (WMS), produces a constellation of distinctive cognitive, neuroanatomical, and electrophysiological features which we explore through the series of studies reported here. In this paper, we focus primarily on the cognitive characteristics of WMS and begin to forge links among these characteristics, the brain, and the genetic basis of the disorder. The distinctive cognitive profile of individuals with WMS includes relative strengths in language and facial processing and profound impairment in spatial cognition. The cognitive profile of abilities, including what is ‘typical’ for individuals with WMS is discussed, but we also highlight areas of variability across the group of individuals with WMS that we have studied. Although the overall cognitive abilities (IQs) of individuals with WMS are typically in the mild-to-moderate range of mental retardation, the peaks and valleys within different cognitive domains make this syndrome especially intriguing to study across levels. Understanding the brain basis (and ultimately the genetic basis) for higher cognitive functioning is the goal we have begun to undertake with this line of interdisciplinary research.

TEORI KECERDASAN, PENDIDIKAN ANAK, DAN KOMUNIKASI DALAM KELUARGA

1970 ◽  
Vol 6 (1) ◽  
Author(s):  
Muskinul Fuad
Keyword(s):  
Multiple Intelligences ◽  
Educational Activity ◽  
Howard Gardner ◽  
Human Beings ◽  
Brain Functions ◽  
Starting Point ◽  
The Family ◽  
Education Today ◽  
The Brain ◽  
Spatial Logics

The education system in Indonesia emphasize on academic intelligence, whichincludes only two or three aspects, more than on the other aspects of intelligence. For thatreason, many children who are not good at academic intelligence, but have good potentials inother aspects of intelligence, do not develop optimally. They are often considered and labeledas "stupid children" by the existing system. This phenomenon is on the contrary to the theoryof multiple intelligences proposed by Howard Gardner, who argues that intelligence is theability to solve various problems in life and produce products or services that are useful invarious aspects of life.Human intelligence is a combination of various general and specific abilities. Thistheory is different from the concept of IQ (intelligence quotient) that involves only languageskills, mathematical, and spatial logics. According to Gardner, there are nine aspects ofintelligence and its potential indicators to be developed by each child born without a braindefect. What Gardner suggested can be considered as a starting point to a perspective thatevery child has a unique individual intelligence. Parents have to treat and educate theirchildren proportionally and equitably. This treatment will lead to a pattern of education that isfriendly to the brain and to the plurality of children’s potential.More than the above points, the notion that multiple intelligences do not just comefrom the brain needs to be followed. Humans actually have different immaterial (spiritual)aspects that do not refer to brain functions. The belief in spiritual aspects and its potentialsmeans that human beings have various capacities and they differ from physical capacities.This is what needs to be addressed from the perspective of education today. The philosophyand perspective on education of the educators, education stakeholders, and especially parents,are the first major issue to be addressed. With this step, every educational activity andcommunication within the family is expected to develop every aspect of children'sintelligence, especially the spiritual intelligence.

scholarly journals The evolution of hierarchical structure building capacity for language and music: a bottom-up perspective

Primates ◽  
2021 ◽  
Author(s):  
Rie Asano
Keyword(s):  
Hierarchical Structure ◽  
Hierarchical Control ◽  
Bottom Up ◽  
Building Capacity ◽  
Cognitive Domains ◽  
Structure Building ◽  
Language And Music ◽  
Directed Action ◽  
Brain Architecture ◽  
The Brain

AbstractA central property of human language is its hierarchical structure. Humans can flexibly combine elements to build a hierarchical structure expressing rich semantics. A hierarchical structure is also considered as playing a key role in many other human cognitive domains. In music, auditory-motor events are combined into hierarchical pitch and/or rhythm structure expressing affect. How did such a hierarchical structure building capacity evolve? This paper investigates this question from a bottom-up perspective based on a set of action-related components as a shared basis underlying cognitive capacities of nonhuman primates and humans. Especially, I argue that the evolution of hierarchical structure building capacity for language and music is tractable for comparative evolutionary study once we focus on the gradual elaboration of shared brain architecture: the cortico-basal ganglia-thalamocortical circuits for hierarchical control of goal-directed action and the dorsal pathways for hierarchical internal models. I suggest that this gradual elaboration of the action-related brain architecture in the context of vocal control and tool-making went hand in hand with amplification of working memory, and made the brain ready for hierarchical structure building in language and music.

scholarly journals Identification of Novel Cathepsin B Inhibitors with Implications in Alzheimer’s Disease: Computational Refining and Biochemical Evaluation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1946
Author(s):  
Nitin Chitranshi ◽  
Ashutosh Kumar ◽  
Samran Sheriff ◽  
Veer Gupta ◽  
Angela Godinez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydrogen Bond ◽  
Virtual Screening ◽  
Cathepsin B ◽  
Amyloid Β ◽  
Proteolytic Degradation ◽  
Hydrogen Bond Acceptor ◽  
Starting Point ◽  
The Brain

Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid β (Aβ) and plaques in the brain, which are pathological hallmarks of Alzheimer’s disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspect for the discovery of new anti-Alzheimer’s drugs. In this study, we have employed mixed-feature ligand-based virtual screening (LBVS) by integrating pharmacophore mapping, docking, and molecular dynamics to detect small, potent molecules that act as cathepsin B inhibitors. The LBVS model was generated by using hydrophobic (HY), hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) features, using a dataset of 24 known cathepsin B inhibitors of both natural and synthetic origins. A validated eight-feature pharmacophore hypothesis (Hypo III) was utilized to screen the Maybridge chemical database. The docking score, MM-PBSA, and MM-GBSA methodology was applied to prioritize the lead compounds as virtual screening hits. These compounds share a common amide scaffold, and showed important interactions with Gln23, Cys29, His110, His111, Glu122, His199, and Trp221. The identified inhibitors were further evaluated for cathepsin-B-inhibitory activity. Our study suggests that pyridine, acetamide, and benzohydrazide compounds could be used as a starting point for the development of novel therapeutics.

scholarly journals Exome sequencing in patients with antiepileptic drug exposure and complex phenotypes

2019 ◽  
Vol 105 (4) ◽  
pp. 384-389 ◽  
Author(s):  
Adam Jackson ◽  
Heather Ward ◽  
Rebecca Louise Bromley ◽  
Charulata Deshpande ◽  
Pradeep Vasudevan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Copy Number ◽  
Developmental Disorders ◽  
Drug Exposure ◽  
Genetic Disorders ◽  
Copy Number Variants ◽  
Copy Number Variant ◽  
In Utero ◽  
Developmental Problems ◽  
Number Of Children

IntroductionFetal anticonvulsant syndrome (FACS) describes the pattern of physical and developmental problems seen in those children exposed to certain antiepileptic drugs (AEDs) in utero. The diagnosis of FACS is a clinical one and so excluding alternative diagnoses such as genetic disorders is essential.MethodsWe reviewed the pathogenicity of reported variants identified on exome sequencing in the Deciphering Developmental Disorders (DDD) Study in 42 children exposed to AEDs in utero, but where a diagnosis other than FACS was suspected. In addition, we analysed chromosome microarray data from 10 patients with FACS seen in a Regional Genetics Service.ResultsSeven children (17%) from the DDD Study had a copy number variant or pathogenic variant in a developmental disorder gene which was considered to explain or partially explain their phenotype. Across the AED exposure types, variants were found in 2/15 (13%) valproate exposed cases and 3/14 (21%) carbamazepine exposed cases. No pathogenic copy number variants were identified in our local sample (n=10).ConclusionsThis study is the first of its kind to analyse the exomes of children with developmental disorders who were exposed to AEDs in utero. Though we acknowledge that the results are subject to bias, a significant number of children were identified with alternate diagnoses which had an impact on counselling and management. We suggest that consideration is given to performing whole exome sequencing as part of the diagnostic work-up for children exposed to AEDs in utero.

scholarly journals Neural Basis of Genetically Determined Visuospatial Construction Deficit in Williams Syndrome

Neuron ◽  
2004 ◽  
Vol 43 (5) ◽  
pp. 623-631 ◽  
Author(s):  
Andreas Meyer-Lindenberg ◽  
Philip Kohn ◽  
Carolyn B. Mervis ◽  
J.Shane Kippenhan ◽  
Rosanna K. Olsen ◽  
...  
Keyword(s):  
Williams Syndrome ◽  
Neural Basis ◽  
Genetically Determined

scholarly journals Anatomical Study of Intrahemispheric Association Fibers in the Brains of Capuchin Monkeys (Sapajussp.)

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Kellen Christina Malheiros Borges ◽  
Hisao Nishijo ◽  
Tales Alexandre Aversi-Ferreira ◽  
Jussara Rocha Ferreira ◽  
Leonardo Ferreira Caixeta
Keyword(s):  
Nonhuman Primates ◽  
Evolutionary Process ◽  
Anatomical Study ◽  
Lateral View ◽  
Superior Longitudinal Fasciculus ◽  
Cognitive Behaviors ◽  
Behavioral Studies ◽  
Inferior Longitudinal Fasciculus ◽  
Association Fibers ◽  
The Brain

Previous studies suggest that the complexity of fiber connections in the brain plays a key role in the evolutionary process of the primate brain and behaviors. The patterns of brain fiber systems have been studied in detail in many nonhuman primates, but not inSapajussp. Behavioral studies indicated thatSapajussp. (bearded capuchins) show highly cognitive behaviors such as tool use comparable to those in other nonhuman primates. To compare the brain fiber systems in capuchins with those in other nonhuman primates and humans, the intrahemispheric fibers systems in 24 cerebral hemispheres ofSapajuswere dissected by a freezing-thawing procedure. Dissection of the hemispheres in lateral view indicated short arcuate fibers, uncinate fasciculus, and inferior longitudinal fasciculus, while that in a medial view indicated short arcuate fibers, the cingulum united with the superior longitudinal fasciculus, and inferior longitudinal fasciculus. The results showed that the fiber systems inSapajusare comparable to those in rhesus and humans, except for a lack of independent superior longitudinal fasciculus and cingulum inSapajus.

scholarly journals Orexin receptor blockers: A tool for lowering alcohol intake and alcohol addictive behavior in the light of preclinical studies

2021 ◽  
Vol 75 (1) ◽  
pp. 959-969
Author(s):  
Kamila Czora-Poczwardowska ◽  
Radosław Kujawski ◽  
Julia Słyńko-Krzyżostaniak ◽  
Przemysław Ł. Mikołajczak ◽  
Michał Szulc
Keyword(s):  
Alcohol Intake ◽  
Selective Reduction ◽  
Optimization Methods ◽  
Sugar Solution ◽  
Behavioral Studies ◽  
Potential Efficacy ◽  
Bioactive Ligands ◽  
Receptor Blockers ◽  
Rats And Mice ◽  
The Brain

Abstract Alcohol use disorder (AUD) is a severe and globally widespread neurological and psychiatric problem. The treatment with currently used drugs often does not bring the expected effect. New optimization methods or directions in pharmacotherapy are still being sought. The group of bioactive ligands, targeted at neuropeptides called orexins (OXs) and their receptors (OXRs), affects a number of functions including ingestion, sleep-wake regulation, as well as the brain reward system which is the basis of addiction. The purpose of this paper is to systematize the knowledge in the field of preclinical behavioral studies on rodents (rats and mice) in several models of alcohol consumption using the OXRs antagonists. The results of the experiments indicated a potential efficacy of particular OXRs antagonists in the AUD treatment, especially those selectively blocking the OX1R. Among them, SB-334867 in the lowest effective dose of 3 mg/kg i.p. was most studied, as shown in the model of two-bottle choice using C57BL/6 mice. Moreover, this compound did not affect the reduction of cognitive functions. GSK1059865 was also involved in the selective reduction of ethanol intake, and simultaneously did not alter the consumption of sugar solution. The other group of selective OX2R antagonists, such as TCS-OX2-29 and LSN2424100, was less efficient. In summary, the OX1R antagonists proved to have the potential in AUD therapy, not only through the reduction of ethanol consumption but also in the treatment of coexisting behavioral and physiological disorders, such as insomnia and anxiety.

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