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Biomedical subjects

J M Fletcher

Publications and source records attributed to J M Fletcher.

At least 19 recordsLinked to original sources
PubMed2001

The functional neural architecture of components of attention in language-processing tasks.

Using functional magnetic resonance imaging we examined three important dimensions of attentional control (selective attention, divided attention, and executive function) in 25 neurologically normal, right-handed men and women, using tasks involving the perception and processing of printed words, spoken words, or both. In the context of language-processing manipulations: selective attention resulted in increased activation at left hemisphere parietal sites as well as at inferior frontal sites, divided attention resulted in additional increases in activation at these same left hemisphere sites and was also uniquely associated with increased activation of homologous sites in the right hemisphere, and executive function (measured during a complex task requiring sequential decision-making) resulted in increased activation at frontal sites relative to all other conditions. Our findings provide support for the belief that specific functional aspects of attentional control in language processing involve widely distributed but distinctive cortical systems, with mechanisms associated with the control of perceptual selectivity involving primarily parietal and inferior frontal sites and executive function engaging specific sites in frontal cortex.

Adult↗
PubMed2001

Attention processes in children with shunted hydrocephalus versus attention deficit-hyperactivity disorder.

Children with congenital hydrocephalus, children with attention deficit-hyperactivity disorder, and normal controls were evaluated with measures of focused attention (Visual Orienting and Detection Task), sustained attention (continuous performance test), and attention shifting (Wisconsin Card Sorting Test). Components from these tasks have been linked to attention systems mediated by anterior or posterior brain networks. Children with congenital hydrocephalus showed an inability to focus and shift attention, which specifically implicated impairment of the disengage and move components of the posterior brain attention system. Children with attention deficit-hyperactivity disorder displayed the expected performance patterns on measures of focused attention once their difficulties with sustained attention were taken into account. However, they showed problems with shifting and sustaining attention, which are commonly associated with the anterior brain attention system.

Achievement↗
PubMed2001

Fasting medium chain acyl-coenzyme A dehydrogenase--deficient children can make ketones.

Medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency classically presents as hypoketotic hypoglycemia. Under-production of ketones has been presumed to be the cause of hypoketosis, but this has never been proven. Stable isotope dilution studies of ketone kinetics were performed on three well children with homozygous 985G MCAD deficiency using 1,3-13C2 sodium acetoacetate and 1,2,3,4-13C4 sodium 3-hydroxybutyrate to ascertain the rates of ketone production, interconversion, and use. All children were fasted for 9 to 11.5 hours before the beginning of the study period. Euglycemia was maintained in all cases. Ketone kinetics were calculated using a two-accessible pool model and showed normal ketone production in all three children compared with published control data from children fasted for a similar length of time. There is no evidence for underproduction or overuse of ketones in these MCAD-deficient children, at least when they are well. We propose that another factor, such as fever, may be required to reduce ketone production and result in the biochemical phenotype recognized in unwell children.

3-Hydroxybutyric Acid↗
PubMed2000

Brain activation profiles in dyslexic children during non-word reading: a magnetic source imaging study.

The purpose of the study was to identify spatiotemporal brain activation profiles associated with phonological decoding in dyslexic children using magnetic source imaging. For this purpose maps of regional cerebral activation were obtained from eleven children diagnosed with dyslexia and ten children without reading problems during engagement in a pseudoword rhyme-matching task. All dyslexic children showed aberrant activation maps consisting of reduced activity in temporoparietal areas in the left hemisphere (including the posterior part of the superior temporal, angular and supramarginal gyri) and increased activity in the right homotopic region. In contrast, the two groups of children did not differ in the degree of activity in basal temporal areas that typically precedes temporoparietal activation. This is the first study to demonstrate the existence of distinct activation profiles associated with phonological decoding in individual dyslexic children.

Adolescent↗
PubMed2000

Brain mechanisms for reading: the role of the superior temporal gyrus in word and pseudoword naming.

The purpose of this study was to test the neurological validity of a dual-route model of reading by asking patients, who were undergoing electrocortical stimulation mapping, to read words with irregular print-to-sound correspondences and pseudowords. Brain activation profiles were also obtained from these patients during an auditory and a visual word recognition task using whole-head magnetic source imaging. We demonstrated that reading is subserved by at least two brain mechanisms that are anatomically dissociable. One mechanism subserves assembled phonology and depends on the activity of the posterior part of the left superior temporal gyrus (STGp), whereas the second is responsible for addressed phonology and does not necessarily involve this region. The contribution of STGp to reading appears to be based on its specialization for phonological analysis operations, involved in the processing of both spoken and written language.

Adult↗
PubMed2000

Reduction of corpus callosum growth after severe traumatic brain injury in children.

OBJECTIVE: To study effects of closed head injury (CHI) severity on development of corpus callosum (CC) in children, using MRI. BACKGROUND: Vulnerability of CC to diffuse axonal injury has been shown in adults and children by neuropathologic and MRI studies. Given continued development of CC through the second decade, serial MRI could characterize effects of CHI on CC growth in children. METHOD: MRI performed at 3 and 36 months after severe (mean age = 10.3 years, n = 25) and mild to moderate (mean age = 9.7 years, n = 28) CHI. Mild to moderate and severe CHI groups did not differ in demographic features. Morphometry of T1-weighted midsagittal CC by two operators with satisfactory interrater reliability yielded uncorrected and corrected CC volume. RESULTS: An interaction of occasion with CHI severity was present as CC area decreased from 3 to 36 months in severely injured children and increased in the mild to moderate CHI group. Uncorrected CC area was correlated with acute CHI severity and functional outcome at 36 months postinjury. CONCLUSIONS: Morphometric measurement of CC area provides a useful index of diffuse injury, which is related to functional outcome of CHI in children.

Brain Injuries↗
PubMed2000

Acute neuroradiologic findings in young children with inflicted or noninflicted traumatic brain injury.

Acute CT/MRI findings were examined in a prospective, longitudinal study of 60 children 0-6 years of age hospitalized for moderate to severe traumatic brain injury (TBI). TBI was categorized as either inflicted (n = 31) or noninflicted (n = 29). Glasgow Coma Scale scores and perinatal history were comparable in both groups. Acute CT/MRI studies were visually inspected by a radiologist blind to group membership. Compared with the noninflicted TBI group, the inflicted TBI group had significantly elevated rates of subdural interhemispheric and convexity hemorrhages as well as signs of pre-existing brain abnormality, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly. Intraparenchymal hemorrhage, shear injury, and skull fractures were more frequent after non-inflicted TBI. Subarachnoid hemorrhage and infarct/edema occurred with comparable frequency in both groups. Characteristic acute neuroimaging findings of inflicted TBI included multiple extraaxial hemorrhages in addition to the mild atrophy, subdural hygromas, and ventriculomegaly that suggest prior brain abnormality.

Brain Edema↗
PubMed2000

Treatment of late-onset nonketotic hyperglycinaemia: effectiveness of imipramine and benzoate.

We report a patient with late-onset nonketotic hyperglycinaemia managed with a sequential approach to drug therapy in placebo-controlled therapeutic trials. Partial response to low-protein diet and sodium benzoate and dramatic response to imipramine are demonstrated, with parental scores on the Developmental Behavioural Checklist falling from the 86th centile before treatment to normal with combined benzoate and imipramine therapy.

Benzoates↗
PubMed2000

Dissociation of frequency and recency processing from list recall after severe closed head injury in children and adolescents.

To investigate judgment of the frequency and recency of events relative to word list recall in children following closed head injury (CHI), 124 children and adolescents, including 79 severe CHI patients (mean age at test = 13.2 years), 27 mild CHI cases (mean age at test = 12.1 years), and 18 uninjured comparison subjects (mean age = 12.8 years) were studied. The mean postinjury interval was 63.6 months for the severe and 46.7 months for the mild CHI groups. The experimental tasks included estimation of the frequency of presentation of words and designs and recency judgment to select the most recently presented of two stimuli on verbal (words) and nonverbal (faces) tasks. To compare frequency and recency judgments to performance on a task which has been shown to be sensitive to CHI severity and age at test, verbal recall was tested using the California Verbal Learning Test-Children's Version. Severity of CHI (group) affected verbal recall across trials and after delays, but had no effect on estimating frequency and isolated effects on judgment of recency. Age was also primarily related to verbal recall. A subgroup of severe CHI patients with frontal lesions was impaired on delayed recall. The results are discussed in relation to previous research on the effects of CHI on processing the frequency and recency of events.

Adolescent↗
PubMed2000

Profiles of cognitive performance associated with reading disability in temporal lobe epilepsy.

92 patients with temporal lobe epilepsy (TLE) were classified into reading deficient (RD; N = 41) and non-reading deficient (no-RD; N = 51) groups. A cutoff of 80 was used to further classify patients as having low average or better (AVG: IQ > 79) or below average (LOW: 69 < IQ < 80) intellectual ability. Differences between RD-AVG and no-RD-AVG patients in profiles of performance on cognitive tests were specific to verbal and non-verbal memory and verbal abilities, but not visuoconstructional and executive abilities. RD-LOW patients exhibited globally reduced abilities. Profiles of performance on cognitive tests were sensitive to side of seizure onset in the no-RD AVG group, but not the RD-AVG or RD-LOW groups. These data suggest that a group of patients with TLE and reduced academic achievement exhibit cognitive deficits suggestive of a language learning disability, and that cognitive tests are less sensitive to side of seizure onset in this group.

Adolescent↗
PubMed2000

Cerebral mechanisms involved in word reading in dyslexic children: a magnetic source imaging approach.

The purpose of the present investigation was to describe spatiotemporal brain activation profiles during word reading using magnetic source imaging (MSI). Ten right-handed dyslexic children with severe phonological decoding problems and eight age-matched non-impaired readers were tested in two recognition tasks, one involving spoken and the other printed words. Dyslexic children's activation profiles during the printed word recognition task consistently featured activation of the left basal temporal cortices followed by activation of the right temporoparietal areas (including the angular gyrus). Non-impaired readers showed predominant activation of left basal followed by left temporoparietal activation. In addition, we were able to rule out the hypothesis that hypoactivation of left temporoparietal areas in dyslexics was due to a more general cerebral dysfunction in these areas. Rather, it seems likely that reading difficulties in developmental dyslexia are associated with an aberrant pattern of functional connectivity between brain areas normally involved in reading, namely ventral visual association cortex and temporoparietal areas in the left hemisphere. The interindividual consistency of activation profiles characteristic of children with dyslexia underlines the potential utility of this technique for examining neurophysiological changes in response to specific educational intervention approaches.

Adolescent↗
PubMed2000

Adrenomedullary function during cognitive testing in attention-deficit/hyperactivity disorder.

OBJECTIVE: Reported correlations between epinephrine (EPI) excretion and classroom performance, the cognition-enhancing effects of EPI infusion, increased EPI excretion with stimulants, and reports of decreased EPI excretion in attention-deficit/hyperactivity disorder (ADHD) suggest that sympathoadrenomedullary function might be altered in ADHD. This hypothesis was tested by examining sympathetic and adrenomedullary functioning during cognitive testing in boys with diagnosed ADHD. METHOD: Urinary excretion of EPI and norepinephrine during a 3-hour cognitive test battery was assessed in 7- to 13-year-old boys. Excretion rates (nanograms per hour per square meter of body surface area) were determined in 200 individuals with ADHD (diagnosed according to DSM-IV criteria), with or without co-occurring oppositional defiant/conduct disorder or learning disorder. A non-ADHD contrast group (n = 51) with similar comorbidity was also studied. RESULTS: Substantially lower (mean +/- SE) urinary EPI excretion was observed in the ADHD-inattentive subtype (n = 71) compared with the control group (200 +/- 22 versus 278 +/- 24 ng/hr/m2; F = 5.99, p = .015, critical alpha = .017). No diagnostic group differences were seen for norepinephrine excretion. Correlational analysis of both parent- and teacher-rated behaviors revealed that inattention factors consistently negatively predicted urinary EPI excretion. CONCLUSIONS: The data extend findings of lower adrenomedullary activity during cognitive challenge in individuals with ADHD and suggest that the alteration is associated with inattentive behavior.

Adolescent↗
PubMed2000

Insights into brain function and neural plasticity using magnetic source imaging.

This review outlines the rationale for the use of magnetoencephalography (MEG) or magnetic source imaging (MSI), a noninvasive functional imaging technique, and the features that any imaging method should display to make a substantial contribution to cognitive neuroscience. After a brief discussion of the basic experimental approach used in the authors' studies, the use of early sensory components of brain magnetic responses is reviewed to address issues of the functional organization of the primary sensory cortices, followed by a comment on the clinical use of these components. Second, normative studies focusing on the late components of magnetic responses for establishing the validity and reliability of MSI maps of the language-specific cortex in normal subjects are reviewed. Third, the authors' investigations of fine spatiotemporal features of brain activation maps, specific to receptive language and to reading, are reviewed. Fourth, experience with presurgical mapping of the language-specific cortex in neurosurgery candidates and in patients undergoing the "Wada" procedure is summarized followed by a comment on the perfect agreement of the MSI maps with those derived by more direct invasive brain mapping procedures. Fifth. MSI-derived evidence of often dramatic, functional reorganization of brain areas subserving both simple sensory and linguistic functions is summarized along with comments on the use of MSI as a means for investigating brain plasticity. Finally, in the sixth section of this review, the authors relate their experience with the use of MSI in deriving brain activation profiles during silent reading of real words and pseudowords that are specific to dyslexic children. The review concludes with a discussion on the further use of MSI in assessing, among other issues, the effectiveness of intervention strategies designed to improve reading fluency in dyslexic children.

Acoustic Stimulation↗
PubMed2000

The angular gyrus in developmental dyslexia: task-specific differences in functional connectivity within posterior cortex.

Converging evidence from neuroimaging studies of developmental dyslexia reveals dysfunction at posterior brain regions centered in and around the angular gyrus in the left hemisphere. We examined functional connectivity (covariance) between the angular gyrus and related occipital and temporal lobe sites, across a series of print tasks that systematically varied demands on phonological assembly. Results indicate that for dyslexic readers a disruption in functional connectivity in the language-dominant left hemisphere is confined to those tasks that make explicit demands on assembly. In contrast, on print tasks that do not require phonological assembly, functional connectivity is strong for both dyslexic and nonimpaired readers. The findings support the view that neurobiological anomalies in developmental dyslexia are largely confined to the phonological-processing domain. In addition, the findings suggest that right-hemisphere posterior regions serve a compensatory role in mediating phonological performance in dyslexic readers.

Adolescent↗
PubMed2000

Volume of focal brain lesions and hippocampal formation in relation to memory function after closed head injury in children.

OBJECTIVES: (1) A study of verbal learning and memory in children who had sustained a closed head injury (CHI) at least 3 months earlier. (2) To relate memory function to focal brain lesion and hippocampal formation volumes using morphometric analysis of MRI. METHODS: A group of 245 children who had been admitted to hospital for CHI graded by the Glasgow coma scale (GCS), including 161 patients with severe and 84 with mild CHI completed the California verbal learning test (CVLT) and underwent MRI which was analysed for focal brain lesion volume independently of memory test data. Brain MRI with 1.5 mm coronal slices obtained in subsets of 25 patients with severe and 25 patients with mild CHI were analysed for hippocampal formation volume. Interoperator reliability in morphometry was satisfactory. RESULTS: Severity of CHI and age at study significantly affected memory performance. Regression analysis showed that bifrontal, left frontal, and right frontal lesion volumes incremented prediction of various learning and memory indices after entering the GCS score and age into the model. Extrafrontal lesion volume did not contribute to predicting memory performance. CONCLUSIONS: Prefrontal lesions contribute to residual impairment of learning and memory after severe CHI in children. Although effects of CHI on hippocampal formation volume might be difficult to demonstrate in non-fatal paediatric CHI, further investigation using functional brain imaging could potentially demonstrate hippocampal dysfunction.

Adolescent↗