Satoshi Sanada

The Rey-Osterrieth Complex Figure as a Measure of Executive Function in Childhood

In adults, the Rey-Osterrieth Complex Figure (ROCF) can be used for the assessment of not only visuoconstructional ability and visual memory, but also executive function in adults. We studied whether ROCF scores also correlated with executive function in childhood. The subjects consisted of 56 patients with various neurological diseases (5 years 7 months-14 years 11 months; mean: 8 years 8 months; M 42, F 14) whose full-scale IQs were 70 or higher (mean: 93.3). All subjects underwent the Wechsler Intelligence Scale for children third edition (WISC-III) and various psychological tests focusing on executive function. We evaluated the ROCF with the Boston Qualitative Scoring System (BQSS). We calculated the partial correlation coefficients between the BQSS Summary Scores and representative scores of other executive function tests, using age as the control variable. Among the scores of the various examinations, the Perseverative Errors of Nelson of the Wisconsin Card Sorting Test, the raw scores of the Mazes (WISC-III), the Digit Span (WISC-III), and the Block Design (WISC-III) were correlated significantly with two to four BQSS Summary Scores (P<0.05 or P<0.01). In contrast, the scores of the Trail Making Test, the Stroop Test, and the Commission Error of Continuous Performance Test-II did not show a significant correlation with any of the BQSS Summary Scores. The ROCF evaluated with the BQSS reflects not only visuoperceptual ability and visuoconstructional ability, but also executive function, especially planning and organization. However, a new BQSS Summary Score should be devised since no existing BQSS index specifically reflects executive functions with an outstandingly strong correlation.

The effects of age on the N200 component of the auditory event-related potentials

This study was undertaken to determine the effects of development and aging on N200 of event-related potentials from childhood to adulthood. Event-related potentials were recorded from 164 normal subjects ranging in age from 4 to 77 years. A total of 127 of the 164 subjects demonstrated N200 peaks. N200 showed marked developmental changes. During childhood, the N200 latency decreased rapidly with age to the minimum (217 +/- 17.3 ms) at 16 years of age, while it was prolonged gradually with age during adulthood. The latency/age slope in the subjects from 5 to 15 years of age was -9.03 ms/year, while +0.97 ms/year in those from 16 to 77. The N200-P300 interpeak latency remained constant in all age groups and showed no age-related changes. The N200 amplitude decreased as age increased. Nineteen young cases showed N200 peaks to the frequent stimuli. Their ages ranged from 5 to 17 years. Our study suggests that N200 is valuable in evaluating the developmental and aging processes in the central nervous system. The results of this study could be used as normative data in clinical practices.

Effects of high-dose antiepileptic drugs on event-related potentials in epileptic children

N200 and P300 of event-related potentials (ERPs) were recorded from 22 epileptic children receiving high-dose antiepileptic drugs. The patients were undergoing monotherapy with supratherapeutic serum level and were not mentally retarded. P300 latency was prolonged in 5 of 8 patients (62.5%) of the carbamazepine (CBZ) group and in 4 of 7 patients (57.1%) of the phenytoin (PHT) group. Only one child of the PHT group showed abnormality in brain-stem auditory evoked potentials (BAEPs). Abnormality of P300 was more frequent than that of BAEP. In patients of the PHT group who underwent examinations consecutively before and after changing the dose, P300 latency was prolonged rapidly when the PHT level exceeded 30 micrograms/ml. This suggested that the prolongation was dose dependent. In all patients of the valproic acid (VPA) group, P300 latency was normal. Only 2 patients of the PHT group had P300 prolongation simultaneously with clinical signs of intoxication. Others demonstrated changes in P300 without symptoms of side effects.

Prenatal exposure to traffic-related air pollution and child behavioral development milestone delays in Japan

Background: Recent studies suggest that prenatal exposure to outdoor air pollution is associated with unfavorable neurodevelopment in children. We examined associations between prenatal exposure to traffic-related air pollution and child behavioral development milestone delays, using data from a nationwide population-based longitudinal survey in Japan, where the participants were recruited in 2001 and followed. Methods: Particulate matter, nitrogen dioxide, and sulfur dioxide concentrations during the 9 months before birth were obtained at the municipality level and assigned to the participants who were born in the corresponding municipality. We analyzed data from singleton births with linked pollution data available (N = 33,911 at the maximum). We used responses to survey questions about age-appropriate behaviors at ages 2.5 and 5.5 years as indicators of behavioral development. We conducted multilevel logistic regression analysis, adjusting for individual and municipality-level variables. Results: Air pollution exposure during gestation was positively associated with the risk of some developmental milestone delays at both ages. Specifically, air pollution was associated with verbal and fine motor development at age 2.5 years, and with behaviors related to inhibition and impulsivity at 5.5 years. In the fully-adjusted models, odds ratios following one-interquartile-range increase in nitrogen dioxide and suspended particulate matter were 1.24 (95% confidence interval: 1.07, 1.43) for inability to compose a two-phrase sentence at ages 2.5 and 1.10 (1.05, 1.16) for inability to express emotions at age 5.5 years, respectively. Conclusions: Prenatal exposure to traffic-related air pollution was associated with behavioral development milestone delays of children in a nationally representative sample in Japan.

Suppression-burst patterns in intractable epilepsy with focal cortical dysplasia

We report on a patient with early-onset spasms in series and partial seizures associated with focal cortical dysplasia whose EEGs showed suppression-burst patterns during early infancy. These electroclinical characteristics suggested a diagnosis of Ohtahara syndrome, but the EEG findings were atypical because of the lack of suppression-burst patterns during wakefulness. In addition, the patient did not have severe psychomotor retardation. With high-dose pyridoxal phosphate therapy, seizures were suppressed and suppression-burst patterns disappeared at 2 months of age. Focal motor seizures recurred later and they often evolved into epilepsia partialis continua. Patients with early-onset intractable seizures associated with suppression-burst patterns on EEGs have several different etiologies, and these patients should be categorized according to their etiology in addition to their syndromic diagnosis.

Predicting executive function task scores with the Rey-Osterrieth Complex Figure.

The Boston Qualitative Scoring System (BQSS) is one of the scoring methods of the Rey-Osterrieth Complex Figure Test (ROCF). With BQSS, 17 qualitative ratings are generated, and subsequently 6 summary scores are calculated by combining several qualitative scores. Previously we showed that 5 of 6 BQSS summary scores were correlated with the scores of the several executive function tests in children. The objective of this study was to develop a new summary score which correlates with the executive function test scores more strongly than the existing summary scores. For this purpose, we conducted multiple regression analysis to predict PEN, CA, DSM of the Wisconsin Card Sorting Test Keio Version, and the Mazes scores from WISC-III, by the BQSS qualitative scores derived from ROCF drawings in copy condition. The subjects were 78 children with various neuropsychological disorders (5 years 5 months-14 years 11 months; mean: 9 years 2 months; F 22, M 56). Significant predictive models were generated for PEN, CA, and Mazes scores. Among them the models for the Mazes scores were the most accurate. The second model for the Mazes scores was most suitable for a new summary score. Its degree-of-freedom-adjusted coefficient of multiple determination and multiple correlation coefficient reached 0.467 and 0.695, respectively. A new summary score should be applied in future studies to evaluate its clinical usefulness.

Multimodal estimation of epileptic foci with dipole localization method and other technique

SummaryTo clarify the diagnostic value of the dipole localization method in estimating the epileptic focus in various types of localization-related epilepsy, dipole analysis of interictal spikes in epileptic patients was performed. Three-layered realistically-shaped models (Scalp-Skull-Brain model, SSB model) were used to compare the results with regional abnormalities revealed by various neuroimaging techniques and clinical manifestations. Subjects were 22 patients with localization-related epilepsy, including 11 cases with localized MRI abnormalities and 9 cases with abnormal SPECT findings. The results of spike dipole location coincided with the clinical findings in 20 of 22 cases. In the two cases with frontal lobe epilepsy, the results did not coincide. In 10 of 11 cases with MRI abnormality dipoles were located within the area of organic lesions. In all 10 cases with SPECT abnormal findings, regional hypoperfusion was found at the area corresponding to the location of the dipole, although SPECT findings showed a wider area as the epileptic focus. In conclusion, dipole estimation using the SSB model can be considered to be a useful technique for noninvasive investigation of epileptic focus.

Executive function in children with pervasive developmental disorder and attention-deficit/hyperactivity disorder assessed by the Keio version of the Wisconsin card sorting test

The Wisconsin card sorting test (WCST) comprehensively examines executive function (EF). The Keio version of the WCST (KWCST) uses fewer cards and presents them in two steps, separated by a short pause during which an instruction is given. Being of short duration, this test is suitable for children with pervasive developmental disorder (PDD) and attention-deficit/hyperactivity disorder (AD/HD), yet few studies have examined the performance of children with such developmental disorders in the second step of a two-step test such as the KWCST. Using the KWCST, this study compares EF in children with PDD (n=52), or AD/HD (n=46) to that in typically developing (TD) children (n=52). Scores for the six indices of this test, including numbers of response cards until the first category achieved (NUCA), total errors (TE), and non-perseverative errors of Nelson (NPEN), were analyzed using ANOVA. Compared to the TD group, scores in the PDD and/or AD/HD groups were significantly lower for all indices except NUCA and NPEN for the first step, and lower for all indices except NUCA for the second step. Moreover, significantly fewer improvements in TE were seen in the PDD group, and significantly fewer improvements in NPEN were seen in the AD/HD group, compared with TD. This study suggests that both PDD and AD/HD make it difficult for children to utilize their experience in the first step and to effectively apply the instruction given before the second step. It also suggests that the two-step nature of the KWCST is clinically important.

Intrauterine Exposure to Methylmercury and Neurocognitive Functions: Minamata Disease.

A large-scale food poisoning caused by methylmercury was identified in Minamata, Japan, in the 1950s. The severe intrauterine exposure cases are well known, although the possible impact of low-to-moderate methylmercury exposure in utero are rarely investigated. We examined neurocognitive functions among 22 participants in Minamata, mainly using an intelligence quotient test (Wechsler Adults Intelligent Scale III), in 2012/2013. The participants tended to score low on the Index score of processing speed (PS) relative to full-scale IQ, and discrepancies between PS and other scores within each participant were observed. The lower score on PS was due to deficits in digit symbol-coding and symbol search and was associated with methylmercury concentration in umbilical cords. The residents who experienced low-to-moderate methylmercury exposure including prenatal one in Minamata manifested deficits in their cognitive functions, processing speed in particular.

Event-related potentials in epileptic children treated with monotherapy

Abstract N200 and P300 of event-related potentials (ERPs) were compared between 73 epileptic children and 73 age-matched normal controls. The former group was composed of patients undergoing monotherapy and having neither mental retardation nor gross organic brain lesion. P300 was not influenced by the types of epileptic syndrome, types of seizure, kinds of antiepileptic drugs (AEDs), frequencies of seizures, EEG abnormality, or durations of illness. In 9 of 24 patients of the carbamazepine (CBZ) group, the P300 latency was prolonged with z -scores >2 above the normal standard mean value. In all other drug groups, the z -scores remained within the level of 2. In 5 of 32 patients with complex partial seizures (CPS), the P300 latency was prolonged. All these patients were receiving CBZ monotherapy. Our results showed that P300 latency could be prolonged in some of the CBZ-treated patients, although statistically significant differences were not observed among the drug groups. These findings suggest that P300 can detect a subtle functional change in the CNS induced by CBZ.