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      Episodes of overtreatment during the first six months in children with congenital hypothyroidism and their relationships with sustained attention and inhibitory control at school age.

      Hormone Research in Pædiatrics
      Child, Congenital Hypothyroidism, blood, psychology, therapy, Dose-Response Relationship, Drug, Executive Function, drug effects, Female, Hormone Replacement Therapy, adverse effects, methods, Humans, Infant, Linear Models, Male, Thyrotropin, Thyroxine, administration & dosage

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          Abstract

          Contradictory results regarding the optimal initial dose of levothyroxine in children with congenital hypothyroidism (CH) hamper the clinical management of these children during their early infancy. We explore the relationships between the initial dose of levothyroxine and endocrine control during the first 6 months and cognition at school age. Fifty children with CH, 14 boys (10+/-3.1 years) and 36 girls (9.7+/-2.6 years), at the Pediatric Endocrine Unit of the Hospital Gregorio Marañón in Madrid were studied. Neurocognitive evaluation was carried out exploring alertness and inhibitory control. The number of episodes of overtreatment during the first 6 months, the initial dose of levothyroxine, etiology and sex were the predictor variables. Inhibitory control was significantly lower in children with CH than in controls. An interaction with gender and etiology was obtained. Alertness had an inverse relationship with the number of episodes of overtreatment with no interaction with gender or etiology. Episodes of overtreatment and not the initial dose of levothyroxine are a risk factor for deficit in alertness whereas subtle inhibitory control deficit seems to be a permanent problem with the current therapeutic approach. Copyright (c) 2010 S. Karger AG, Basel.

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          Thyroid hormone receptors in brain development and function.

          Thyroid hormones are important during development of the mammalian brain, acting on migration and differentiation of neural cells, synaptogenesis, and myelination. The actions of thyroid hormones are mediated through nuclear thyroid hormone receptors (TRs) and regulation of gene expression. The purpose of this article is to review the role of TRs in brain maturation. In developing humans maternal and fetal thyroid glands provide thyroid hormones to the fetal brain, but the timing of receptor ontogeny agrees with clinical data on the importance of the maternal thyroid gland before midgestation. Several TR isoforms, which are encoded by the THRA and THRB genes, are expressed in the brain, with the most common being TRalpha1. Deletion of TRalpha1 in rodents is not, however, equivalent to hormone deprivation and, paradoxically, even prevents the effects of hypothyroidism. Unliganded receptor activity is, therefore, probably an important factor in causing the harmful effects of hypothyroidism. Accordingly, expression of a mutant receptor with impaired triiodothyronine (T(3)) binding and dominant negative activity affected cerebellar development and motor performance. TRs are also involved in adult brain function. TRalpha1 deletion, or expression of a dominant negative mutant receptor, induces consistent behavioral changes in adult mice, leading to severe anxiety and morphological changes in the hippocampus.
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            Attentional networks

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              The functional integration of the anterior cingulate cortex during conflict processing.

              Although functional activation of the anterior cingulate cortex (ACC) related to conflict processing has been studied extensively, the functional integration of the subdivisions of the ACC and other brain regions during conditions of conflict is still unclear. In this study, participants performed a task designed to elicit conflict processing by using flanker interference on target response while they were scanned using event-related functional magnetic resonance imaging. The physiological response of several brain regions in terms of an interaction between conflict processing and activity of the anterior rostral cingulate zone (RCZa) of the ACC, and the effective connectivity between this zone and other regions were examined using psychophysiological interaction analysis and dynamic causal modeling, respectively. There was significant integration of the RCZa with the caudal cingulate zone (CCZ) of the ACC and other brain regions such as the lateral prefrontal, primary, and supplementary motor areas above and beyond the main effect of conflict and baseline connectivity. The intrinsic connectivity from the RCZa to the CCZ was modulated by the context of conflict. These findings suggest that conflict processing is associated with the effective contribution of the RCZa to the neuronal activity of CCZ, as well as other cortical regions.
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