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Biomedical subjects

J M Fletcher

Publications and source records attributed to J M Fletcher.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Neuroanatomic and neuropsychological outcome in school-age children with achondroplasia.

We previously reported on cognitive and respiratory factors in a series of infants with achondroplasia (ACH). We now present the results of neuropsychological evaluation and magnetic resonance imaging in 16 school-age children with ACH, 7 of whom had been included as infants in our previous report. We examined the neuroanatomic and cognitive status of this sample, as well as the predictive stability of the prior infant assessment. Seventeen normally developing children of average stature and 21 preterm children with arrested (compensated, unshunted) hydrocephalus constituted the comparison groups. Brain volumes of children with ACH were significantly larger than those of the comparison groups. In addition, children with ACH exhibited kinking of the medulla and neuroanatomic abnormalities consistent with arrested hydrocephalus, including enlarged ventricles and hypoplasia of the corpus callosum. Cognitive abilities at school age were average, although mild deficits were seen on visual-spatial tasks, similar to those obtained by the hydrocephalic comparison group. Only gross motor coordination deficits distinguished the ACH group from the hydrocephalic controls. Infant assessment overestimated later school-age IQ scores in those infants with ACH who scored above average. These findings point to generally preserved cognitive skills in selected children with ACH at early school age, although children with ACH should be evaluated individually as they are at risk for cognitive, academic, and motor deficits.

Achondroplasia↗
PubMed1999

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.

CONTEXT: Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES: Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. RESULTS: Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS: Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.

Adult↗
PubMed1999

Corpus callosum damage and interhemispheric transfer of information following closed head injury in children.

We evaluated the relationship of corpus callosum atrophy and/or lesions on magnetic resonance imaging (MRI) to functional hemispheric disconnection following closed head injury (CHI) in 51 pediatric patients, including mild CHI, moderate to severe CHI with extracallosal lesions, and moderate to severe CHI with callosal atrophy and/or lesions. Interhemispheric transfer of information was assessed using auditory, motor, tactile, and visual tests in patients and in 16 uninjured children. Total and regional callosal areas were measured from the midsagittal MRI slice by morphometry. The corpus callosum lesion group demonstrated a greater right ear advantage on verbal dichotic listening than all other groups. Areas of the posterior corpus callosum were negatively correlated with laterality indices of verbal dichotic listening performance and tachistoscopic identification of verbal material. The relationship of corpus callosum atrophy and/or lesions to asymmetry in dichotic listening is consistent with previous investigation of posttraumatic hemispheric disconnection effects in adults.

Adolescent↗
PubMed1999

Pitfalls in the use of 2-octynoic acid as an in vivo model of medium-chain acyl-coenzyme A dehydrogenase deficiency: ketone turnover and metabolite studies in the rat.

2-Octynoic acid was administered by intraperitoneal injection to fasted Sprague-Dawley rats in an attempt to simulate medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The resultant urine organic acid profile showed a mild dicarboxylic aciduria but lacked the glycine conjugates characteristic of MCAD deficiency. Further studies with infused 13C(4)-3-hydroxybutyrate and 13C(2)-acetoacetate demonstrated reduced ketone production in treated rats compared with control animals. Although plasma ketone body concentrations were low in treated rats, plasma free fatty acids were also low, thereby providing diminished substrate for ketone production. This is the reverse of the finding in children with MCAD deficiency, who have low levels of plasma ketones despite elevated free fatty acids. These animal studies were therefore not helpful in improving our understanding of ketone body kinetics in children with MCAD deficiency.

3-Hydroxybutyric Acid↗