Cardiac cell fate control by the imidazoline I1 receptor/nischarin : application in cardiac pathology

La moxonidine, un médicament antihypertenseur sympatholytique de type imidazolinique, agit au niveau de la médulla du tronc cérébral pour diminuer la pression artérielle, suite à l’activation sélective du récepteur aux imidazolines I1 (récepteur I1, aussi nommé nischarine). Traitement avec de la moxonidine prévient le développement de l’hypertrophie du ventricule gauche chez des rats hypertendus (SHR), associé à une diminution de la synthèse et une élévation transitoire de la fragmentation d’ADN, des effets antiprolifératifs et apoptotiques. Ces effets se présentent probablement chez les fibroblastes, car l’apoptose des cardiomyocytes pourrait détériorer la fonction cardiaque. Ces effets apparaissent aussi avec des doses non hypotensives de moxonidine, suggérant l’existence d’effets cardiaques directes. Le récepteur I1 se trouvé aussi dans les tissus cardiaques; son activation ex vivo par la moxonidine stimule la libération de l’ANP, ce qui montre que les récepteurs I1 cardiaques sont fonctionnels malgré l’absence de stimulation centrale. Sur la base de ces informations, en plus du i) rôle des peptides natriurétiques comme inhibiteurs de l’apoptose cardiaque et ii) des études qui lient le récepteur I1 avec la maintenance de la matrix extracellulaire, on propose que, à part les effets sympatholytiques centrales, les récepteurs I1 cardiaques peuvent contrôler la croissance-mort cellulaire. L’activation du récepteur I1 peut retarder la progression des cardiopathies vers la défaillance cardiaque, en inhibant des signaux mal adaptatifs de prolifération et apoptose. Des études ont été effectuées pour : 1. Explorer les effets in vivo sur la structure et la fonction cardiaque suite au traitement avec moxonidine chez le SHR et le hamster cardiomyopathique. 2. Définir les voies de signalisation impliquées dans les changements secondaires au traitement avec moxonidine, spécifiquement sur les marqueurs inflammatoires et les voies de signalisation régulant la croissance et la survie cellulaire (MAPK et Akt). 3. Explorer les effets in vitro de la surexpression et l’activation du récepteur I1 sur la survie cellulaire dans des cellules HEK293. 4. Rechercher la localisation, régulation et implication dans la croissance-mort cellulaire du récepteur I1 in vitro (cardiomyocytes et fibroblastes), en réponse aux stimuli associés au remodelage cardiaque : norépinephrine, cytokines (IL-1β, TNF-α) et oxydants (H2O2). Nos études démontrent que la moxonidine, en doses hypotensives et non-hypotensives, améliore la structure et la performance cardiaque chez le SHR par des mécanismes impliquant l’inhibition des cytokines et des voies de signalisation p38 MAPK et Akt. Chez le hamster cardiomyopathique, la moxonidine améliore la fonction cardiaque, module la réponse inflammatoire/anti-inflammatoire et atténue la mort cellulaire et la fibrose cardiaque. Les cellules HEK293 surexprimant la nischarine survivent et prolifèrent plus en réponse à la moxonidine; cet effet est associé à l’inhibition des voies ERK, JNK et p38 MAPK. La surexpression de la nischarine protège aussi de la mort cellulaire induite par le TNF-α, l’IL-1β et le H2O2. En outre, le récepteur I1 s’exprime dans les cardiomyocytes et fibroblastes, son activation inhibe la mort des cardiomyocytes et la prolifération des fibroblastes induite par la norépinephrine, par des effets différentiels sur les MAPK et l’Akt. Dans des conditions inflammatoires, la moxonidine/récepteur aux imidazolines I1 protège les cardiomyocytes et facilite l’élimination des myofibroblastes par des effets contraires sur JNK, p38 MAPK et iNOS. Ces études démontrent le potentiel du récepteur I1/nischarine comme cible anti-hypertrophique et anti-fibrose à niveau cardiaque. L’identification des mécanismes cardioprotecteurs de la nischarine peut amener au développement des traitements basés sur la surexpression de la nischarine chez des patients avec hypertrophie ventriculaire. Finalement, même si l’effet antihypertenseur des agonistes du récepteur I1 centraux est salutaire, le développement de nouveaux agonistes cardiosélectifs du récepteur I1 pourrait donner des bénéfices additionnels chez des patients non hypertendus.

Objective neuropsychological deficits in post-traumatic stress disorder and mild traumatic brain injury: what remains beyond symptom similarity?

This exploratory study intends to characterize the neuropsychological profile in persons with post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) using objective measures of cognitive performance. A neuropsychological battery of tests for attention, memory and executive functions was administered to four groups: PTSD (n = 25), mTBI (n = 19), subjects with two formal diagnoses: Post-traumatic Stress Disorder and Mild Traumatic Brain Injury (mTBI/PTSD) (n = 6) and controls (n = 25). Confounding variables, such as medical, developmental or neurological antecedents, were controlled and measures of co-morbid conditions, such as depression and anxiety, were considered. The PTSD and mTBI/PTSD groups reported more anxiety and depressive symptoms. They also presented more cognitive deficits than the mTBI group. Since the two PTSD groups differ in severity of PTSD symptoms but not in severity of depression and anxiety symptoms, the PTSD condition could not be considered as the unique factor affecting the results. The findings underline the importance of controlling for confounding medical and psychological co-morbidities in the evaluation and treatment of PTSD populations, especially when a concomitant mTBI is also suspected.

Implication de Syngap1 dans la transmission GABAergique et la plasticité synaptique

La déficience intellectuelle affecte de 1 à 3% de la population mondiale, ce qui en fait le trouble cognitif le plus commun de l’enfance. Notre groupe à découvert que des mutations dans le gène SYNGAP1 sont une cause fréquente de déficience intellectuelle non-syndromique, qui compte pour 1-3% de l’ensemble des cas. À titre d’exemple, le syndrome du X fragile, qui est la cause monogénique la plus fréquente de déficience intellectuelle, compte pour environ 2% des cas. Plusieurs patients affectés au niveau de SYNGAP1 présentent également des symptômes de l’autisme et d’une forme d’épilepsie. Notre groupe a également montré que SYNGAP1 cause la déficience intellectuelle par un mécanisme d’haploinsuffisance. SYNGAP1 code pour une protéine exprimée exclusivement dans le cerveau qui interagit avec la sous-unité GluN2B des récepteurs glutamatergique de type NMDA (NMDAR). SYNGAP1 possède une activité activatrice de Ras-GTPase qui régule négativement Ras au niveau des synapses excitatrices. Les souris hétérozygotes pour Syngap1 (souris Syngap1+/-) présentent des anomalies de comportement et des déficits cognitifs, ce qui en fait un bon modèle d’étude. Plusieurs études rapportent que l’haploinsuffisance de Syngap1 affecte le développement cérébral en perturbant l’activité et la plasticité des neurones excitateurs. Le déséquilibre excitation/inhibition est une théorie émergente de l’origine de la déficience intellectuelle et de l’autisme. Cependant, plusieurs groupes y compris le nôtre ont rapporté que Syngap1 est également exprimé dans au moins une sous-population d’interneurones GABAergiques. Notre hypothèse était donc que l’haploinsuffisance de Syngap1 dans les interneurones contribuerait en partie aux déficits cognitifs et au déséquilibre d’excitation/inhibition observés chez les souris Syngap1+/-. Pour tester cette hypothèse, nous avons généré un modèle de souris transgéniques dont l’expression de Syngap1 a été diminuée uniquement dans les interneurones dérivés des éminences ganglionnaires médianes qui expriment le facteur de transcription Nkx2.1 (souris Tg(Nkx2,1-Cre);Syngap1). Nous avons observé une diminution des courants postsynaptiques inhibiteurs miniatures (mIPSCs) au niveau des cellules pyramidales des couches 2/3 du cortex somatosensoriel primaire (S1) et dans le CA1 de l’hippocampe des souris Tg(Nkx2,1-Cre);Syngap1. Ces résultats supportent donc l’hypothèse selon laquelle la perte de Syngap1 dans les interneurones contribue au déséquilibre d’excitation/inhibition. De manière intéressante, nous avons également observé que les courants postsynaptiques excitateurs miniatures (mEPSCs) étaient augmentés dans le cortex S1, mais diminués dans le CA1 de l’hippocampe. Par la suite, nous avons testé si les mécanismes de plasticité synaptique qui sous-tendraient l’apprentissage étaient affectés par l’haploinsuffisance de Syngap1 dans les interneurones. Nous avons pu montrer que la potentialisation à long terme (LTP) NMDAR-dépendante était diminuée chez les souris Tg(Nkx2,1-Cre);Syngap1, sans que la dépression à long terme (LTD) NMDAR-dépendante soit affectée. Nous avons également montré que l’application d’un bloqueur des récepteurs GABAA renversait en partie le déficit de LTP rapporté chez les souris Syngap1+/-, suggérant qu’un déficit de désinhibition serait présent chez ces souris. L’ensemble de ces résultats supporte un rôle de Syngap1 dans les interneurones qui contribue aux déficits observés chez les souris affectées par l’haploinsuffisance de Syngap1.

Dopamine Receptor Gene Expression In Streptozotocin Induced Diabetic Rats And Its Role In Insulin Secretion

Diabetes Mellitus is a metabolic disorder associated with insulin deficiency, which not.only affects the carbohydrate metabolism but also is associated with various central and peripheral complications. Chronic hyperglycemia during diabetes mellitus is a major initiator of diabetic microvascular complications like retinopathy, neuropathy, The central nervous system (CNS) neurotransmitters play an important role in the regulation of glucose homeostasis. These neurotransmitters mediate rapid intracellular communications not only within the central nervous system but also in the peripheral tissues. They exert their function through receptors present in both neuronal and non neuronal cell surface that trigger second messenger signaling pathways. Dopamine is a neurotransmitter that has been implicated in various central neuronal degenerative disorders like Parkinson's disease and behavioral diseases like Schizophrenia. Dopamine is synthesised from tyrosine, stored in vesicles in axon terminals and released when the neuron is depolarised. Dopamine interacts with specific membrane receptors to produce its effect. Dopamine plays an important role both centrally and peripherally. The recent identification of five dopamine receptor subtypes provides a basis for understanding dopamine's central and peripheral actions . Dopamine receptors are classified into two major groups : DA D1 like and DA D2 like. Dopamine D1 like receptors consists of DA D1 and DA D5 receptors . Dopamine D2 like receptors consists of DA D2, DA D3 and DA D4 receptors. Stimulation of the DA D1 receptor gives rise to increased production of cAMP. Dopamine D2 receptors inhibit cAMP production, but activate the inositol phosphate second messenger system . Impairment of central dopamine neurotransmission causes muscle rigidity, hormonal regulation , thought disorder and cocaine addiction. Peripheral dopamine receptors mediate changes in blood flow, glomerular filtration rate, sodium excretion and catecholamine release. The dopamine D2 receptors increased in the corpus striatum and cerebral cortex but decreased in the hypothalamus and brain stem indicating their involvement in regulating insulin secretion. Dopamine D2 receptor which has a stimulatory effecton insulin secretion decreased in the pancreatic islets during diabetes. Our in vitro studies confirmed the stimulatory role of dopamine D2 receptors in stimulation of glucose induced insulin secretion. A detailed study at the molecular level on the mechanisms involved in the role of dopamine in insulin secretion, its functional modification could lead to therapeutic interventions that will have immense clinical importance.

Cholinergic receptor subtypes functional regulation in spinal cord injured monoplegic rats

The present study deals with the Cholinergic Receptor subtypes functional regulation in spinal cord injured monoplegic rats: Effect of 5-HT GABA and bone marrow cells.Spinal cord injury causes permanent and irrevocable motor deficits and neurodegeneration. Disruption of the spinal cord leads to diminished transmission of descending control from the brain to motor neurons and ascending sensory information. Behavioural studies showed deficits in motor control and coordination in SCI rats. Cholinergic system plays an important role in SCI, the evaluation of which provides valuable insight on the underlying mechanisms of motor deficit that occur during SCI. The cholinergic transmission was studied by assessing the muscarinic and nicotinic receptors; cholinergic enzymes- ChAT and AChE; second messenger enzyme PLC; transcription factor CREB and second messengers - IP3, cAMP and cGMP. We observed a decrease in the cholinergic transmission in the brain and spinal cord of SCI rats. The disrupted cholinergic system is the indicative of motor deficit and neuronal degeneration in the spinal cord and brain regions. SCI mediated oxidative stress and apoptosis leads to neuronal degeneration in SCI rats. The decreased expression of anti oxidant enzymes – SOD, GPx and neuronal cell survival factors - BDNF, GDNF, IGF-1, Akt and cyclin D2 along with increased expression of apoptotic factors – Bax, caspase-8, TNFa and NF-kB augmented the neuronal degeneration in SCI condition. BMC administration in combination with 5-HT and GABA in SCI rats showed a reversal in the impaired cholinergic neurotransmission and reduced the oxidative stress and apoptosis. It also enhanced the expression of cell survival factors in the spinal cord region. In SCI rats treated with 5-HT and GABA, the transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the spinal cord. Neurotrophic factors and anti-apoptotic elements in SCI rats treated with 5-HT and GABA along with BMC rendered neuroprotective effects accompanied by improvement in behavioural deficits. This resulted in a significant reversal of altered cholinergic neurotransmission in SCI. The restorative and neuro protective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of SCI.

Serotonin receptor subtypes functional regulation and oxidative stress mediated apoptosis in 6-hydroxydopamine lesioned Parkinsonian rats

Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the SNpc resulting in severe motor impairments. Serotonergic system plays an important regulatory role in the pathophysiology of PD in rats, the evaluation of which provides valuable insight on the underlying mechanisms of motor, cognitive and memory deficits in PD. We observed a decrease in 5-HT content in the brain regions of 6-OHDA infused rat compared to control. The decreased 5-HT content resulted in a decrease of total 5-HT, 5-HT2A receptors and 5-HTT function and an increase of 5-HT2C receptor function. 5-HT receptor subtypes - 5-HT2A and 5-HT2C receptors have differential regulatory role on the modulation of DA neurotransmission in different brain regions during PD. Our observation of impaired serotonergic neurotransmission in SNpc, corpus striatum, cerebral cortex, hippocampus, cerebellum and brain stem demonstrate that although PD primarily results from neurodegeneration in the SNpc, the associated neurochemical changes in other areas of the brain significantly contributes to the different motor and non motor symptoms of PD. The antioxidant enzymes – SOD, CAT and GPx showed significant down regulation which indicates increased oxidative damage resulting in neurodegeneration. We also observed an increase in the level of lipid peroxidation. Reduced expression of anti-apoptotic Akt and enhanced expression of NF-B resulting from oxidative stress caused an activation of caspase-8 thus leading the cells to neurodegeneration by apoptosis. BMC administration in combination with 5-HT and GABA to PD rats showed reversal of the impaired serotonergic neurotransmission and oxidative stress mediated apoptosis. The transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the SNpc along with an increase in DA content and an enhanced expression of TH. Neurotrophic factors – BDNF and GDNF rendered neuroprotective effects accompanied by improvement in behavioural deficits indicating a significant reversal of altered dopaminergic and serotonergic neurotransmission in PD. The restorative and neuroprotective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of PD.

Withania somnitera and withanolide a mediated restoration of AMPA and NMDA receptor function in pilocarpine induced temporal lobe epilepsy

The onset of spontaneous seizures triggers a cascade of molecular and cellular events that eventually leads to neuronal injury and cognitive decline. The present study investigated the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring behavioural deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. The subdued performance in behavioural tests shows impaired motor coordination and memory. Histopathological investigations revealed significant neuronal loss in hippocampus of epileptic rats indicating glutamate mediated excitotoxicity. The treatment with WS and WA restored behavioural deficit and ameliorated neuronal loss. An altered redox homeostasis leading to oxidative stress is a hallmark of TLE. The antioxidant potential was afflicted in epileptic rats, evident from altered activity of SOD and CAT, down regulation of SOD and GPX expression and enhanced lipid peroxidation. The antioxidant property of WS and WA restored altered antioxidant capacity. Alteration in GDH activity and down regulation of GLAST expression resulted in enhanced glutamate content in the brain regions. The metabolism of glutamate was altered in the form of down regulated GAD expression. The alteration in synthesis, transport and metabolism resulted in further increase of the glutamate concentration at the synapse leading to glutamate mediated excitotoxicity. The decreased NMDA and AMPA receptor binding and down regulated NMDA R1, NMDA 2B and AMPA (GluR2) mRNA expression indicated altered glutamergic receptor function. The treatment with WS and WA reversed altered glutamergic receptor function, synthesis, transport and metabolism. The enhanced levels of second messenger IP3 responsible for Ca2+ mediated toxicity was reversed after treatment with WS and WA. Neurotoxics concentration of glutamate resulted in up regulation of pro apoptotic factors Bax and Caspase 8 and down regulation of anti apoptotic factor Akt resulting in neuronal death. The treatment with WS and WA resulted in activation of Akt and down regulation of Bax and caspase 8 leading to blocking of apoptotic pathway. The treatment with WS and WA resulted in reduced seizure frequency and amelioration of associated alterations suggesting the therapeutic role of Withania somnifera in temporal lobe epilepsy

Serotonin Receptor Gene Expression And Insulin Function In Streptozotocin Induced Diabetic Rats

Recent studies have established a fimctional correlation of serotonergic and adrenergic function in the brain regions with insulin secretion in diabetic rats (Vahabzadeh et al., 1995). Administration of 5-HT”. agonist 8-OH-DPAT to conscious rats caused an increase in blood glucose level. This increase in blood glucose is due to inhibition of insulin secretion by increased circulating EPI (Chaouloff et al., 1990a; Chaouloff et al., 1990d; Chaoulo1T& Jeanrenaud, 1987). The increase in EPI is brought about by increased sympathetic stimulation. This increase can lead to increased sympatho-medullary stimulation thereby inhibiting insulin release (Bauhelal & Mir, 1993, Bauhelal & Mir, 1990a; Chaouloffet al., 1990d). Also, studies have shown that Gi protein in the liver has been decreased in diabetes which will increase gluconeogenesis and glycogenolysis thereby causing hyperglycaemia (Pennington, 1987). Serotonergic control is suggested to exert different effects on insulin secretion according to the activation of different receptor subclasses (Pontiroli et al., 1975). In addition to this mechanism, the secretion of insulin is dependent on the turnover ratio of endogenous 5-hydroxy tryptophan (5-HTP) to 5-HT in the pancreatic islets (Jance er al., 1980). The reports so far stated does not explain the complete mechanism and the subclass of 5-HT receptors whose expression regulate insulin secretion in a diabetic state. Also, there is no report of a direct regulation of insulin secretion by 5-HT from the pancreatic islets even though there are reports stating that the pancreatic islets is a rich source of 5-HT (Bird et al., 1980). Therefore, in the present study the mechanism by which 5-HT and its receptors regulate insulin secretion from pancreatic [3-cells was investigated. Our results led to the following hypotheses by which 5-HT and its receptors regulate the insulin secretion.

Perfil neuropsicológico de personas adultas con VIH/SIDA

Los déficit neurológicos en el virus de inmunodeficiencia humana VIH, específicamente las alteraciones en el funcionamiento cognitivo, han estado presentes desde el inicio de su propagación y han sido una de las principales manifestaciones a lo largo de todas las etapas del virus. No obstante, gracias a los avances de la terapia antirretroviral se ha dado un aumento de la expectativa de vida de los pacientes, dándose de la misma manera un incremento en los déficits anteriormente mencionados. El objetivo del presente estudio es describir el perfil neuropsicológico de los pacientes con VIH y establecer si existen relaciones entre las funciones que se encuentren deterioradas, el tiempo de diagnóstico y la terapia antiretroviral. Para esto se llevo a cabo un estudio descriptivo de tipo exploratorio con el fin de medir las características de las funciones neuropsicológicas en un grupo de 24 pacientes pertenecientes al programa especial B24 del Hospital Universitario Mayor y Hospital de Barrios Unidos MÉDERI en Bogotá, Colombia. Para esto, se utilizó un protocolo de pruebas neuropsicológicas: Mini Mental StateExamination (MMSE), WAIS-III (sub-pruebas dígitos, letras y números, aritmética y semejanzas), Curva de aprendizaje auditivo verbal de Rey (RAVLT), WMS-III (sub-pruebas de recobro de historias y Localización), TMT A y B, Set Test de Isaacs, Figura Compleja de Rey y Test de Stroop. Dentro de los resultados se encontró que la medida de edad fue de 50 con un total de 19 hombres y 5 mujeres. Las funciones con mayor predominio de deterioro fueron la atención sostenida y alternante, la memoria declarativa, las funciones ejecutivas (específicamente en el control inhibitorio) y la velocidad de procesamiento, los pacientes presentan un rango de deterioro cognitivo leve (GDS 3). Se concluyó que el perfil de deterioro es mixto y que es necesario ampliar la muestra para obtener resultados más precisos en cuanto a las diferencias de acuerdo al tiempo de diagnóstico y la terapia antiretroviral.

A educação inclusiva e a hiperactividade no jardim de infância

RESUMO: Propomos com este trabalho conhecer e aprofundar conhecimentos, através duma investigação-acção, relativamente à problemática em estudo - Perturbação de Hiperactividade com Défice de Atenção (PHDA). Também procurámos mostrar, através da intervenção, que o educador pode auxiliar no desenvolvimento e aprendizagem de uma criança com um diagnóstico de PHDA. Realizámos uma pesquisa bibliográfica sobre esta Perturbação, com uma breve perspectiva histórica, sobre o que é a PHDA, o diagnóstico, os subtipos e problemas associados e a intervenção em crianças com esta problemática. Pesquisámos, também, estratégias educativas de como actuar a nível pedagógico com esta criança e com o grupo onde se encontra incluída. Demos uma grande centralidade ao trabalho empírico, através da pesquisa documental, observações, entrevistas e sociometria. De seguida, elaborámos um projecto de investigação-acção, para o grupo onde a criança está incluída, utilizando estratégias de educação inclusiva, de modo a colmatar problemas comportamentais e de aprendizagem, derivados de défices de atenção e de concentração do grupo, através do grupo. Todo este processo deu resultados positivos, a nível dos comportamentos sociais e das aprendizagens académicas do grupo e do aluno desencadeador do Trabalho Projecto. Obrigou a uma acção, reflexão, acção que desencadeou uma procura e experimentação sistemática para dar resposta aos problemas surgidos, o que ajudou ao meu desenvolvimento pessoal e profissional e a uma vontade de investir mais e melhor no desencadeamento de práticas de educação cada vez mais inclusivas. ABSTRACT: With this paper, we want to learn, using the investigation-action, about the team we are working with, that is Perturbation of Hyperactivity and Deficit of Attention (PHDA). We also want to show that it is possible to help the children with the PHDA in their learning process using the right intervention. We searched for different opinions on this team, its history, how to diagnostic it and the different problems that this children can have. We also search for different strategies to teach the students with this problem as well as the others of the group. We gave special attention to the empirical work. For this reason we used the documental research, the observation, interviews and sociometry. After this we prepared the action research project for the group of children that work with the PHDA child. To do so, we used different inclusion strategies so that we could help him improving his behavior and learning process using the help of other students. On the end we had positive results in the behavior and also in the learning process with the group and the student who we based this work on. We used action/reflection/action that helped us to find out about the PHDA and the different strategies to try to solve this problem. All of this helped me as a teacher and as a person. It gave me the will to keep looking for better and different inclusive strategies.

Problems in the coupling of eye and hand in the sequential movements of children with developmental coordination disorder

Background: Shifting gaze and attention ahead of the hand is a natural component in the performance of skilled manual actions. Very few studies have examined the precise co-ordination between the eye and hand in children with Developmental Coordination Disorder (DCD). Methods This study directly assessed the maturity of eye-hand co-ordination in children with DCD. A double-step pointing task was used to investigate the coupling of the eye and hand in 7-year-old children with and without DCD. Sequential targets were presented on a computer screen, and eye and hand movements were recorded simultaneously. Results There were no differences between typically developing (TD) and DCD groups when completing fast single-target tasks. There were very few differences in the completion of the first movement in the double-step tasks, but differences did occur during the second sequential movement. One factor appeared to be the propensity for the DCD children to delay their hand movement until some period after the eye had landed on the target. This resulted in a marked increase in eye-hand lead during the second movement, disrupting the close coupling and leading to a slower and less accurate hand movement among children with DCD. Conclusions In contrast to skilled adults, both groups of children preferred to foveate the target prior to initiating a hand movement if time allowed. The TD children, however, were more able to reduce this foveation period and shift towards a feedforward mode of control for hand movements. The children with DCD persevered with a look-then-move strategy, which led to an increase in error. For the group of DCD children in this study, there was no evidence of a problem in speed or accuracy of simple movements, but there was a difficulty in concatenating the sequential shifts of gaze and hand required for the completion of everyday tasks or typical assessment items.

Expressive versus receptive language skills in specific reading disorder

Despite ample research into the language skills of children with specific reading disorder no studies so far have investigated whether there may be a difference between expressive and receptive language skills in this population. Yet, neuro-anatomical models would predict that children who have specific reading disorder which is not associated with movement or attention difficulties, would have lower receptive language skills than expressive. This study investigates the difference between expressive and receptive language skills in a sample of 17 children with specific reading difficulty aged between 7 and 12 years. They were administered a battery of two receptive and two expressive language measures. The results showed that as the neuro-anatomical model would predict, the children scored significantly lower on tests of receptive than on tests of expressive language skills.

Orientation coding: a specific deficit in Williams syndrome?

Williams syndrome (WS) is a rare genetic disorder with a unique cognitive profile in which verbal abilities are markedly stronger than visuospatial abilities. This study investigated the claim that orientation coding is a specific deficit within the visuospatial domain in WS. Experiment I employed a simplified version of the Benton Judgement of Line Orientation task and a control, length-matching task. Results demonstrated comparable levels of orientation matching performance in the group with WS and a group of typically developing (TD) controls matched by nonverbal ability, although it is possible that floor effects masked group differences. A group difference was observed in the length-matching task due to stronger performance from the control group. Experiment 2 employed an orientation-discrimination task and a length-discrimination task. Contrary to previous reports, the results showed that individuals with WS were able to code by orientation to a comparable level as that of their matched controls. This demonstrates that, although some impairment is apparent, orientation coding does not represent a specific deficit in WS. Comparison between Experiments I and 2 suggests that orientation coding is vulnerable to task complexity. However, once again, this vulnerability does not appear to be specific to the population with WS, as it was also apparent in the TD controls.

Who knows best? Awareness of divided attention difficulty in a neurological rehabilitation setting

Objective: To explore whether patients relearning to walk after acquired brain injury and showing cognitive-motor interference were aware of divided attention difficulty; whether their perceptions concurred with those of treating staff. Design: Patients and neurophysiotherapists (from rehabilitation and disabled wards) completed questionnaires. Factor analyses were applied to responses. Correlations between responses, clinical measures and experimental decrements were examined. Results: Patient/staff responses showed some agreement; staff reported higher levels of perceived difficulty; responses conformed to two factors. One factor (staff/patients alike) reflected expectations about functional/motor status and did not correlate with decrements. The other factor (patients) correlated significantly with dual-task motor decrement, suggesting some genuine awareness of difficulty (cognitive performance prioritized over motor control). The other factor (staff) correlated significantly with cognitive decrement (gait prioritized over sustained attention). Conclusions: Despite some inaccurate estimation of susceptibility; patients and staff do exhibit awareness of divided attention difficulty, but with a limited degree of concurrence. In fact, our results suggest that patients and staff may be sensitive to different aspects of the deficit. Rather than 'Who knows best?', it is a question of 'Who knows what?.

Spatial representation and attention in toddlers with Williams syndrome and Down syndrome

The nature of the spatial representations that underlie simple visually guided actions early in life was investigated in toddlers with Williams syndrome (WS), Down syndrome (DS), and healthy chronological age- and mental age-matched controls, through the use of a "double-step" saccade paradigm. The experiment tested the hypothesis that, compared to typically developing infants and toddlers, and toddlers with DS, those with WS display a deficit in using spatial representations to guide actions. Levels of sustained attention were also measured within these groups, to establish whether differences in levels of engagement influenced performance on the double-step saccade task. The results showed that toddlers with WS were unable to combine extra-retinal information with retinal information to the same extent as the other groups, and displayed evidence of other deficits in saccade planning, suggesting a greater reliance on sub-cortical mechanisms than the other populations. Results also indicated that their exploration of the visual environment is less developed. The sustained attention task revealed shorter and fewer periods of sustained attention in toddlers with DS, but not those with WS, suggesting that WS performance on the double-step saccade task is not explained by poorer engagement. The findings are also discussed in relation to a possible attention disengagement deficit in WS toddlers. Our study highlights the importance of studying genetic disorders early in development. (C) 2002 Elsevier Science Ltd. All rights reserved.