Activación Hemisférica Cerebral en Adultos Jóvenes Mientras Ejecutan Tareas Ortográficas Utilizando fMRI / Hemispheric Brain Activation in Young Adults While Performing Orthographic Tasks Using fMRI

Resumen El dominio del lenguaje escrito se basa en la consolidación de representaciones neurales complejas de los patrones ortográficos de las palabras. En virtud de explorar las características presentes en procesos neurales relacionados con la especialización ortográfica, se estudiaron con métodos de imagen por resonancia magnética funcional los niveles neurales de activación intrahemisférica de 27 jóvenes con alto y bajo rendimiento ortográfico mientras ejecutaban tareas ortográficas. Los resultados sugieren que, en participantes con alto rendimiento ortográfico, la intensidad de activación neural en el hemisferio izquierdo no difiere ante el estímulo de palabras o pseudohomófonos (palabras con error ortográfico); en cambio, difieren cuando se emiten respuestas correctas vs. incorrectas. En participantes con bajo rendimiento ortográfico no se encontró diferencia interhemisférica en ninguna tarea. Se encontró tendencia de que los participantes con bajo rendimiento ortográfico tienen mayor dispersión de la activación neural, respecto a los participantes con alto rendimiento, en el hemisferio derecho e izquierdo, además, en participantes con bajo rendimiento ortográfico se encontró tendencia de que la detección consciente aumenta la variación de la activación neural; sin embargo, no se encontró evidencia estadística concluyente. Este estudio ha abonado a la evidencia de la existencia de la especialización neural orientada a habilidades ortográficas.

Abstract The written language domain is based on the consolidation of complex neural representations of words' orthographic patterns. Here, we studied the characteristics and differences of the neural activation levels that occur in the neural processes related to orthographic specialization, with functional magnetic resonance imaging, in each hemisphere, of 27 young adults with low and high orthographic abilities when they performed orthographic tasks. The results suggest that in high-orthographic-performance participants' left hemispheric neural activation does not vary between words and pseudohomophones; otherwise, their neural activation variates in incorrect vs. correct responses. There were not found interhemispheric differences in low-orthographic-performance participants where they performed any type of task. There were some tendency in the low-orthographic-performance participants to have greater neural activation dispersion, regarding the high-orthographic-performance participants, in both hemispheres, also, there were found tendency in low-orthographic-performance participants to have greater neural activation variation in explicit tasks; nevertheless, there is not enough conclusive statistic evidence. This study increases the evidence of lateralized neural specialization of orthographic abilities.

Rapid automatized naming and lexical decision in children from an electrophysiological perspective.

Rapid Automatized Naming (RAN) deficits have been associated with less developed orthographic abilities that may affect lexical decisions. The effects of Spanish-speaking children's RAN performance on lexical decisions were evaluated by analyzing ERP and behavioral measures. Based upon their naming speed in four RAN tasks, 28 normal IQ, right-handed, 7-year-old children were selected and divided uniformly into two groups: average-naming (AN), and slow-naming (SN). ERPs were obtained during a lexical decision task consisting of 100 strings of four sequentially-presented letters that completed words (50 trials) or pseudowords (also 50 trials). The SN group showed major reading difficulties when compared to the AN group, as well as a significantly lower number of correct responses and slower reaction times in the lexical task. Two main ERP components were observed: parietal N320, interpreted as analogous to N170/N200; and a subsequent P3-like component (P500) with a higher amplitude for pseudowords, which probably reflects higher cognitive demands. Better reading comprehension and fewer misread pseudowords correlated with minor N320 latencies, while lower N320 amplitudes for words correlated with faster reading speeds, lower naming times and fewer errors while reading a text. The present results suggest that naming speed and ERP seem to be valuable in distinguishing early orthographic stored code retrieval abilities through a lexical decision task. Moreover, RAN and ERP emerge as accurate tools for evaluating reading processes in the early stages of reading acquisition.

[Methylphenidate and short-term memory in young females with attention deficit hyperactivity disorder. A study using functional magnetic resonance imaging]. / Metilfenidato y memoria a corto plazo en mujeres jovenes con trastorno por deficit de atencion/hiperactividad. Estudio de resonancia magnetica funcional.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) is a common behavioral disorder found mainly in males, thus current knowledge on its clinical expression in female adults is extremely limited. AIM. To evaluate the behavioral and neural substrates associated with the performance of a short-term memory task in female ADHD adults, with and without methylphenidate exposure, with respect to a control group. SUBJECTS AND METHODS: Two groups of eight young right-handed, female, university students with ADHD and healthy controls matched by age, gender, handedness and academic level, voluntarily participated. All subjects performed twice an easy auditory short-term memory task (ADHD group without, and 90 minutes post-intake of methylphenidate 0.4 mg/kg in a counterbalanced order). The BOLD-fMRI response was used as a measure of neural activity during task performance. RESULTS: ADHD subjects showed a tendency to improve their performances under medication, showing an increased widespread functional activation, especially relevant over left frontal and cerebellar areas, in comparison with control subjects. CONCLUSIONS: Methylphenidate slightly improves short-term memory task performance in adult female ADHD subjects by modifying underlying neural functioning patterns.

Metilfenidato y memoria a corto plazo en mujeres jóvenes con trastorno por déficit de atención/hiperactividad. Estudio de resonancia magnética funcional / Methylphenidate and short-term memory in young females with attention deficit hyperactivity disorder. A study using functional magnetic resonance imaging

Introducción. El trastorno por déficit de atención/hiperactividad (TDAH) afecta predominantemente al sexo masculino, por lo que el conocimiento acerca de su expresión clínica y los efectos del tratamiento en el sexo femenino es muy limitado. Objetivo. Evaluar la respuesta funcional asociada a la ejecución de una tarea sencilla de memoria a corto plazo en mujeres con TDAH sin y bajo la exposición a metilfenidato respecto a un grupo control sano. Sujetos y métodos. Ocho mujeres universitarias, diestras, con diagnóstico de TDAH subtipo inatento y un grupo de controles sanos ejecutaron una tarea auditiva de memoria a corto plazo en dos ocasiones (sin y con ingestión de una dosis terapéutica de metilfenidato en el grupo con TDAH) mientras se registraba la respuesta funcional cerebral con la técnica BOLD de resonancia magnética funcional. Resultados. El grupo con TDAH mostró una tendencia a mejorar la ejecución basal de la tarea con la administración del medicamento. El grupo con TDAH medicado incrementó su actividad funcional en lóbulos frontales, temporal bilateral, parietal derecho y cerebelo izquierdo respecto a los niveles obtenidos durante la ejecución sin metilfenidato. En contraste, los controles sanos mostraron menor activación en el lóbulo frontal bilateral y parietal derecho durante la segunda ejecución de la tarea. Conclusión. El metilfenidato genera una activación funcional más amplia en mujeres adultas con TDAH que coincide con una tendencia a la mejoría en la ejecución conductual de una tarea sencilla de memoria a corto plazo (AU)

Introduction. Attention deficit/hyperactivity disorder (ADHD) is a common behavioral disorder found mainly in males, thus current knowledge on its clinical expression in female adults is extremely limited. Aim. To evaluate the behavioral and neural substrates associated with the performance of a short-term memory task in female ADHD adults, with and without methylphenidate exposure, with respect to a control group. Subjects and methods. Two groups of eight young right-handed, female, university students with ADHD and healthy controls matched by age, gender, handedness and academic level, voluntarily participated. All subjects performed twice an easy auditory short-term memory task (ADHD group without, and 90 minutes post-intake of methylphenidate 0.4 mg/kg in a counterbalanced order). The BOLD-fMRI response was used as a measure of neural activity during task performance. Results. ADHD subjects showed a tendency to improve their performances under medication, showing an increased widespread functional activation, especially relevant over left frontal and cerebellar areas, in comparison with control subjects. Conclusions. Methylphenidate slightly improves short-term memory task performance in adult female ADHD subjects by modifying underlying neural functioning patterns (AU)

Time reproduction disturbances in ADHD children: an ERP study.

Sixteen ADHD children and a control group were asked to reproduce the varying time duration of successively presented visual stimuli. Time estimation was poorer in ADHD children, who showed more impulsive errors. ERPs exhibited similar grand-mean waveforms for both groups during the estimating period, but they were significantly different during the reproducing stage, when an early positive wave over frontal regions characterized the control group, interpreted as memory-guided motor output, followed by a slow negativity probably reflecting an inhibitory motor closure process, both probably involving central executive networks that seem to be improperly activated in ADHD children.

Event-related brain potentials in normal children during detection of inverse serial digits.

Three inverse serial digit detection tasks were evaluated with event-related brain potentials (ERPs) in 15 11-year-old children to determine how the increase of perceptual or memory demands could modify detection processing. Reaction times were significantly longer for the task that used visual blurring, compared to that with a greater memory demand. Difference-ERPs (target minus non-target conditions) showed three significant parietal components; one earlier positive peak at 162 ms interpreted as an index of working memory load; a same polarity 295 ms peak which probably represents a P3 analogous and a subsequent negative polarity component (520 ms) possibly involved with motor preparation. A fourth difference-component was a frontal positive peak at 680 ms, interpreted as related to task difficulty.

Event-related brain potentials during a continuous performance test (CPT) task in normal children.

BACKGROUND: Continuous Performance Test (CPT) is a commonly used paradigm to assess attention disorders that could involve working memory processes. METHODS: Event-related potentials (ERPs) during a CPT (X-AX) test were obtained in 16 healthy male students, with ages ranging from 9 to 11 years (X = 10.3). In grouped averaged ERPs, an endogenous slow positive potential was recorded in the first task (infrequent letter detection); maximum was at 460 msec with a slight lateralization tendency toward left parietal area. In the second task (target detection with an A as warning signal), an early (maximum at 330 msec) and more acute peak was detected without evidence of any lateralization. RESULTS: Reaction times were significantly shorter for the second task. Electrophysiologic differences between both target conditions showed an early, remarkable, and statistically significant component located at the parietal area at 340 msec. CONCLUSIONS: These ERPs findings could be interpreted as correlates with working memory processes in children.

Molecular detection of respiratory syncytial virus in postmortem lung tissue samples from Mexican children deceased with pneumonia.

BACKGROUND: Respiratory syncytial virus (RSV) is the major viral cause of severe respiratory infections in children younger than 2 years of age. Nevertheless there are not enough epidemiologic data about the role of RSV as a cause of infantile mortality from pneumonia, mainly in young children from developing countries Aim. To determine the frequency of RSV infection in lung tissue samples from Mexican children deceased with pneumonia, by reverse transcription (RT) and PCR. METHODS: Postmortem lung tissue samples from 98 children younger than 2 years of age who died of pneumonia during the period of 1989 to 1997 were studied. Paraffin was removed with xylene from 10-microm lung sections, the total RNA was extracted and complementary DNA was obtained by RT reaction. A nested PCR with the use of oligonucleotides specific for the F glycoprotein gene was developed. Samples negatives for RSV were tested for the absence of polymerase inhibitors and for complementary DNA integrity. RESULTS: Twenty-nine of the 98 (30%) children deceased with pneumonia were positive for RSV by RT-PCR; 8 were detected from 13 (62%) children with histopathologic diagnosis of viral pneumonia and 21 from 85 (25%) children with histopathologic diagnosis of bacterial pneumonia (P = 0.018). There was no significant difference in RSV infection according to age groups or seasonal pattern. CONCLUSIONS: RSV infection is frequent in Mexican children younger than 2 years of age who died of pneumonia. Although RSV was more common in viral pneumonia, mixed infections with RSV and bacterial pneumonia were also common.

Serum antibody as a marker of protection against natural rotavirus infection and disease.

To determine whether naturally acquired serum IgA and IgG antibodies were associated with protection against rotavirus infection and illness, a cohort of 200 Mexican infants was monitored weekly for rotavirus excretion and diarrhea from birth to age 2 years. Serum samples collected during the first week after birth and every 4 months were tested for anti-rotavirus IgA and IgG. Children with an IgA titer >1:800 had a lower risk of rotavirus infection (adjusted relative risk [aRR], 0.21; P<.001) and diarrhea (aRR, 0. 16; P=.01) and were protected completely against moderate-to-severe diarrhea. However, children with an IgG titer >1:6400 were protected against rotavirus infection (aRR, 0.51; P<.001) but not against rotavirus diarrhea. Protective antibody titers were achieved after 2 consecutive symptomatic or asymptomatic rotavirus infections. These findings indicate that serum anti-rotavirus antibody, especially IgA, was a marker of protection against rotavirus infection and moderate-to-severe diarrhea.

Transitory cognitive impairment in epileptic children during a CPT task.

EEGs and behavioral responses were studied in two sex matched groups of 58 epileptic and 20 healthy children between 8 and 12 years of age, during the execution of a go-no go CPT (X; A-X) task to determine transitory cognitive impairment (TCI) incidence. Paroxysmal discharges were found on 87.9% and 5% of the EEGs in the epileptic and control groups respectively, with no differences related to sex. The predominant EEG findings with respect to paroxysmal discharges were the association of two or more types of paroxysms with frequency higher than 5/minute, an average duration less than 0.5 second and topographical distribution over temporal-parietal-occipital areas without significant interhemispheric differences. TCI was detected in 36.2% of epileptic children. The epileptic group showed significantly higher numbers of behavioral errors and longer reaction times (RTs) in relation to the control group. Analyzing RTs on the two blocks of the task, linear discriminant analysis showed an acceptable classification of TCI incidence between groups.

A prospective study of astrovirus diarrhea of infancy in Mexico City.

AIM: To describe the epidemiologic and clinical characteristics of astrovirus-associated diarrhea in a cohort of young children from a periurban community in Mexico City. METHODS: From November, 1988, through December, 1991, a total of 214 children were enrolled in a longitudinal study of diarrhea and monitored from birth to 18 months of age. A stool specimen was collected during each episode of diarrhea. Specimens from a total of 510 diarrhea episodes were tested for astrovirus by enzyme immunoassay and examined for other enteric pathogens. The antigenic types of astrovirus were determined by a typing enzyme immunoassay. RESULTS: Astrovirus was detected in 26 (5%) of 510 diarrhea episodes, with an incidence rate of 0.1 episode/child year; the highest rate was in children 13 to 18 months of age. Astrovirus-associated diarrhea was characterized by a median of 4 stools (range, 2 to 10) during the first 24 h, a median duration of 3 days (range, 1 to 21), vomiting (20%), and fever (7%). No cases of dehydration or repeat symptomatic infections were observed. Coinfection with another pathogen was detected in 11 of the 26 episodes (42%). Serotype 2 (35%) was most common, followed by serotypes 4 (15%), 3 (11%), and 1 and 5 (4% each); 31% were nontypable. Astrovirus-associated diarrhea was less severe, as measured by the number of stools (4.3 +/- 1.9), than diarrhea caused by rotavirus (7.1 +/- 2.8) or when coinfections occurred (5.5 +/- 1.6; P = 0.008). CONCLUSIONS: Astrovirus was associated with 5% of the episodes of diarrhea in this cohort of young Mexican children and presented as a mild secretory diarrhea. Five predominant antigenic types were detected with type 2 being the most common.

Rotavirus infection in infants as protection against subsequent infections.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in infants. To provide a base line for assessing the efficacy of rotavirus vaccines, we evaluated the protection that is conferred by natural rotavirus infection. METHODS: We monitored 200 Mexican infants from birth to two years of age by weekly home visits and stool collections. A physician assessed the severity of any episodes of diarrhea and collected additional stool specimens for testing by enzyme immunoassay and typing of strains. Serum collected during the first week of life and every four months thereafter was tested for antirotavirus IgA and IgG. RESULTS: A total of 316 rotavirus infections were detected on the basis of the fecal excretion of virus (56 percent) or a serologic response (77 percent), of which 52 percent were first and 48 percent repeated infections. Children with one, two, or three previous infections had progressively lower risks of both subsequent rotavirus infection (adjusted relative risk, 0.62, 0.40, and 0.34, respectively) and diarrhea (adjusted relative risk, 0.23, 0.17, and 0.08) than children who had no previous infections. No child had moderate-to-severe diarrhea after two infections, whether symptomatic or asymptomatic. Subsequent infections were significantly less severe than first infections (P=0.024), and second infections were more likely to be caused by another G type (P=0.054). CONCLUSION: In infants, natural rotavirus infection confers protection against subsequent infection. This protection increases with each new infection and reduces the severity of the diarrhea.

Study of Norwalk-related viruses in Mexican children.

Two-hundred Mexican children monitored from birth to 2 years of age in a cohort study of diarrhea were tested for Norwalk virus (NV) and Norwalk-related virus infection. Blood was collected quarterly and tested by an enzyme immunoassay (EIA) using the recombinant NV (rNV) particles as antigen. Stool was collected weekly and tested by an EIA using hyperimmune anti-sera from animals immunized with rNV and a reverse transcription-polymerase chain reaction (RT-PCR) with primers in the RNA polymerase region of NV. A high prevalence of serum antibody to NV (85% at age 2 years) was found by the antibody EIA. In 54 stool specimens selected from children who developed a high titer of serum antibody to rNV, none was positive for NV by the antigen EIA, but 6 yielded products by the RT-PCR. One stool specimen (MX virus) yielded a 3.3 kb RT-PCR product from the 3' end of the viral genome. The MX virus cDNA has a genomic organization like other caliciviruses. Sequence comparison showed that MX virus shares 80% nucleic acid and 91% amino acid sequence identity with Snow Mountain agent (SMA), but only 62% and 60% identity, respectively, with NV in the RNA polymerase region, suggesting that MX virus is a SMA-like virus.

Immediate responses of endothelial cells to hypoxia and reoxygenation: an in vitro model of cellular dysfunction.

We have studied endothelial functions and integrity under clinically relevant levels of acute and profound hypoxia. Bovine aortic endothelial cells (EC) grown on microcarrier beads were exposed for 15-min intervals to normoxic (20% O2) or hypoxic (1-2% O2) medium. Control intervals were followed by four hypoxic and then four normoxic intervals for reoxygenation. Prostacyclin release from EC significantly decreased after only 15 min of hypoxia and remained low despite reoxygenation. This decrease in prostacyclin release was not coincident with decreased viable cells (Trypan blue exclusion) or with increased cell lysis (increased lactate dehydrogenase) after hypoxia or reoxygenation. When the medium was supplemented with 30 microM arachidonate (saturating concentration), prostacyclin release still significantly decreased after 30 min of hypoxia but returned to baseline levels by 30 min of reoxygenation. Similar results were obtained for thromboxane B2 release. These data suggest that 1) EC decrease prostacyclin release during acute, profound hypoxia, 2) EC decrease prostaglandin production during hypoxia despite abundant exogenous arachidonate, and 3) recovery of prostaglandin production is dependent on exogenous arachidonate during reoxygenation.

Indirect estimation of thyroid hormone-binding proteins to calculate free thyroxine index: comparison of nonisotopic methods that use labeled thyroxine ("T-uptake")

There are many alternative ways of estimating free thyroxine (T4) when thyrotropin screening results are abnormal. In addition to free T4 immunoassays, the menu of most automated immunoassay instruments includes a nonisotopic version of the original triiodothyronine (T3)-uptake assay called "T-uptake." We evaluated the ability of five such assays (Access, ES-300, IMx, Magnum Opus, and Stratus) to accurately estimate the free thyroxine index (FTI) in euthyroid, hyperthyroid, and hypothyroid patients with abnormal concentrations of thyroid hormone-binding proteins, and in patients with nonthyroidal illness. For comparison, we calculated a similar FTI, using either T3-uptake or direct measurement of thyroxine-binding globulin (TBG). Euthyroid reference ranges were comparable. Of euthyroid patients with increased TBG, 12-32% and 5-20% had increased or suppressed FTI, respectively, depending on the T-uptake method used. Except for IMx, 6-35% of hypothyroid patients with increased TBG had inappropriately increased FTI. Patients with nonthyroidal illness had comparable results regardless of the method used, and T-uptake methods were variably affected by known inhibitors of thyroid hormone binding. The most reliable T-uptake method appeared to be the IMx, which, despite claims that it measures all thyroid hormone-binding proteins, correlated best with TBG concentrations.

Asymptomatic Shigella infections in a cohort of Mexican children younger than two years of age.

The proportion of Shigella infections that occur asymptomatically in young children has not been established. A community-based cohort study of 367 infants was followed prospectively by weekly home visits from January, 1990, through December, 1991. Stool samples were collected weekly and when diarrhea occurred and were tested for Shigella and other enteropathogens. There were 2925 child months of observation and 65 episodes of Shigella infection. There were 3.1 episodes/100 child months during the warm season (May through September) and 0.97 episode/100 child months during the cold season. Shigella infections were rare during the first 6 months of life but increased with age (P < 0.0001). Overall 55% of detected infections were asymptomatic. The proportion of infections that were asymptomatic increased as age increased (P < 0.01). Symptom status was not significantly associated with Shigella species or season. All isolates from symptomatic and asymptomatic children had the 120- to 140-megadalton virulence plasmid. We conclude that infections with virulent strains of Shigella are commonly asymptomatic in Mexican children during the first 2 years of life.

PIP: During January 1990-December 1991, each week, field workers visited the home of 367 children aged 0-24 months from a periurban area southwest of Mexico City (San Pedro Martir and San Andres Totoltepec, Tlalpan) and collected stool specimens from them to determine whether Shigella infections are often asymptomatic. The crude incidence rate of diarrhea, regardless of etiology, was 29 episodes/100 child months during the warmer and rainy months (May-September), while it was 21 episodes/100 child months for the rest of the year (October-April) (relative risk [RR] =1.38). 53 of all children (l4%) had 65 Shigella infections. The overall monthly incidence of symptomatic and asymptomatic Shigella infection was higher during May-September than October-April (3.13 vs. 0.97 episodes/100 children; RR = 3.22). 55% of all Shigella infections (36) were asymptomatic. 32% developed secretory-type diarrhea and 13% had blood present in the stool. The incidence of Shigella infections grew as did the age (0.4-8.2 episodes/100 child months for 0-6 month olds to 18-24 month olds; p 0.0001). The proportion of asymptomatic Shigella infections also increased with age (33% for 0-6 month olds, 40% for 7-12 month olds, 46% for 13-18 month olds, and 78% for 18-24 month olds; p 0.01). Shigella sonnei, S. flexneri, and S. boydii were the only species detected. The 120-140 megadalton virulence plasmid was present in all isolates from asymptomatic and symptomatic children. Mixed infections were rather common in both asymptomatic (47%) and symptomatic (45%) children. Among infants aged less than 12 year months, breast feeding infants were less likely to be infected with Shigella than nonbreast feeding infants (RR = 2.41). On the other hand, among children aged 12-24 months, nonbreast feeding was associated with a lower risk of Shigella infection (RR = 0.69). These findings show that Shigella infections in Mexican children aged 0-24 months range from asymptomatic infections to secretory diarrhea to bloody diarrhea.