Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

<p>Abstract</p> <p>Background</p> <p>Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.</p> <p>Methods</p> <p>Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT + CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the δ, θ, α1, α2, β and γ frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.</p> <p>Results</p> <p>In the CT + CRT group, relative θ power was slightly increased (p = 0.069) and α2 power was significantly decreased (p = 0.006). The CT + CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional θ and α2 powers (0.471 < r < 0.697). A significant association between decreased regional α2 power and less attentional fluctuations was found for CT + CRT patients as well as controls (0.078 < r < 0.666). Patients treated with CT alone displayed a power spectrum similar to controls, except for a significantly increased level of left frontal α2 power (p = 0.030).</p> <p>Conclusions</p> <p>The tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early‐onset dementia. The CT group showed no signs of early aging.</p

Does Cognitive Impairment Explain Behavioral and Social Problems of Children with Neurofibromatosis Type 1?

Thirty NF1-patients (mean age 11.7 years, SD = 3.3) and 30 healthy controls (mean age 12.5 years, SD = 3.1) were assessed on social skills, autistic traits, hyperactivity-inattention, emotional problems, conduct problems, and peer problems. Cognitive control, information processing speed, and social information processing were measured using 5 computer tasks. GLM analyses of variance showed significant group differences, to the disadvantage of NF1-patients, on all measures of behavior, social functioning and cognition. General cognitive ability (a composite score of processing speed, social information processing, and cognitive control) accounted for group differences in emotional problems, whereas social information processing accounted for group differences in conduct problems. Although reductions were observed for group differences in other aspects of behavior and social functioning after control for (specific) cognitive abilities, group differences remained evident. Training of cognitive abilities may help reducing certain social and behavioral problems of children with NF1, but further refinement regarding associations between specific aspects of cognition and specific social and behavioral outcomes is required

Effect of the Size of Clods Contained Covering Soil on the Seedling Emergence of Rice Plant Sown under Upland Field Condition

水稲農林23号を用いて, 覆土の土塊の大きさが, 乾田に深播き(覆土7cm)された個体の出芽ならびに幼苗諸器官の長さに及ぼす影響について, 覆土が3cmの場合と比較しながら検討した。乾田に播種された種子が大きい土塊で覆土されると, 覆土が3cmの場合には鞘葉の伸長が抑制される。しかし, 不完全葉はほとんどの個体で3cm以上に伸長する。また大土塊の間隙が小土塊で充足された場合は, 鞘葉および不完全葉ともに, 大土塊だけの場合よりも長くなる。その結果, すべての区の出芽率は, 播種後12日目には90%以上に達する。覆土が7cmの場合には, 覆土の土塊が大きくても, 鞘葉および不完全葉は覆土が3cmの場合よりも著しく長くなる。その結果, 第1本葉が不完全葉から抽出する位置が高められる。しかし, 鞘葉および不完全葉の伸長のみによっては出芽することはできず, 出芽するためには, 第2節間および第1本葉が伸長しなければならない。覆土の土塊が大きい場合には, 第2節間の伸長が抑制される。と同時に, 出芽までの間に幼芽の伸長を妨げる土塊の数も多くなるので, 出芽率は著しく低下する。しかし, 大土塊の間隙が小さい土塊によって充足されると, 第2節間が著しく長くなり, 第1本葉をおしあげる。その結果, 出芽率は単一土塊の場合に比べて著しく高まる。以上の結果と土壌中への光の侵入量との関係について, 若干考察した。 / This experiment was carried out to clarify the effects of size of clods in covering soil on the emergence and the elongation of rice seedling sown under upland field condition in pot (10cm×10cm×12cm) culture. Variety used was Norin No. 23. Seeds were covered with 3cm and 7cm depth of soil. In the case of 3cm in depth of seeding, if seeds were covered with larger clods, the elongation of coleoptile was inhibited, but the profile elongated longer than 3cm. When gaps between larger clods were filled with smaller clods, the length of coleoptile and profile became longer. Consequently, the emergence percentage of all plots reached more than 90% the 12th day after seeding. In the case of 7cm in depth of seeding, if seeds were covered with larger clods, coleoptile or profile elongated to 3 to 4cm in length, but the elongation of second internode was inhibited. As a result, the emergence percentage decreased significantly. When gaps between larger clods were filled with smaller clods, however, the length of second internode increased and first leaf was pushed up through the soil by second internode. Consequently, the emergence percentage increased significantly

Neuropsychological assessment of attention in children with spina bifida

<p>Abstract</p> <p>Background</p> <p>Children with the severe form of spina bifida (SBM: spina bifida with myelomeningocele with accompanying hydrocephalus) may manifest attention deficits, and have a similar psychological profile to children with hydrocephalus due to other etiologies. It is unclear to what extent tests to assess attention in SBM are confounded by the accompanying cognitive or visual-motor impairments. The aim of this study was to analyse attention functions by administering two different types of attention tests, one with high and the other with low cognitive and motor requirements. This enabled the possible interaction between attention and cognitive and motor impairment to be assessed.</p> <p>Methods</p> <p>The study group comprised 31 children with SBM with shunted hydrocephalus. Twenty children with SB-only formed a closely matched comparison group. Of these, 19 children with SBM and 18 with SB had a full-scale IQ (FSIQ) higher than 70. All had undergone spinal surgery and all children with SBM had been shunted within the first months of life. Between 6 and 15 years of age, the children were assessed on focused and sustained attention, encoding, and distractibility/impulsivity, using both traditional tests and computerized attention tests.</p> <p>Results</p> <p>Compared to the SB group, attention scores of children with SBM were lower on the traditional tests, but when interfering cognitive and visual-motor requirements were eliminated using the computerised tasks, most differences disappeared. Furthermore, in contrast to traditional attention tasks, computerized tests showed no significant correlations with IQ-scores and visual-motor skills.</p> <p>Conclusion</p> <p>Assessment of attention functions in children with SBM by traditional tests may be misleading, because this paediatric population with complex cerebral malformations has difficulty with the cognitive and visual-motor requirements. To control for these interactions, the use of both traditional and computerized attention tests is recommended.</p

Speed, Variability, and Timing of Motor Output in ADHD: Which Measures are Useful for Endophenotypic Research?

Attention-Deficit/Hyperactivity Disorder (ADHD) shares a genetic basis with motor coordination problems and probably motor timing problems. In line with this, comparable problems in motor timing should be observed in first degree relatives and might, therefore, form a suitable endophenotypic candidate. This hypothesis was investigated in 238 ADHD-families (545 children) and 147 control-families (271 children). A motor timing task was administered, in which children had to produce a 1,000 ms interval. In addition to this task, two basic motor tasks were administered to examine speed and variability of motor output, when no timing component was required. Results indicated that variability in motor timing is a useful endophenotypic candidate: It was clearly associated with ADHD, it was also present in non-affected siblings, and it correlated within families. Accuracy (under- versus over-production) in motor timing appeared less useful: Even though accuracy was associated with ADHD (probands and affected siblings had a tendency to under-produce the 1,000 ms interval compared to controls), non-affected siblings did not differ from controls and sibling correlations were only marginally significant. Slow and variable motor output without timing component also appears present in ADHD, but not in non-affected siblings, suggesting these deficits not to be related to a familial vulnerability for ADHD. Deficits in motor timing could not be explained by deficits already present in basic motor output without a timing component. This suggests abnormalities in motor timing were predominantly related to deficient motor timing processes and not to general deficient motor functioning. The finding that deficits in motor timing run in ADHD-families suggests this to be a fruitful domain for further exploration in relation to the genetic underpinnings of ADHD

Effects of maternal and paternal smoking on attentional control in children with and without ADHD

Maternal smoking during pregnancy is a risk factor for attention-deficit/hyperactivity disorder (ADHD), but data on its adverse effects on cognitive functioning are sparse and inconsistent. Since the effect of maternal smoking during pregnancy may be due to correlated genetic risk factors rather than being a pure environmental effect, we examined the effect of prenatal exposure to smoking on attentional control, taking into account the effects of both maternal and paternal smoking, and examined whether these effects were genetically mediated by parental genotypes. We further examined whether the effect of prenatal exposure to smoking on attentional control interacted with genotypes of the child. Participants were 79 children with ADHD, ascertained for the International Multi-centre ADHD Gene project (IMAGE), and 105 normal controls. Attentional control was assessed by a visual continuous performance task. Three genetic risk factors for ADHD (DRD4 7-repeat allele of the exon 3 variable number of tandem repeats (VNTR), DAT1 10/10 genotype of the VNTR located in the 3′ untranslated region, and the DAT1 6/6 genotype of the intron 8 VNTR) were included in the analyses. Paternal smoking had a negative effect on attentional control in children with ADHD and this effect appeared to be mediated by genetic risk factors. The prenatal smoking effect did not interact with genotypes of the child. Maternal smoking had no main effect on attentional control, which may be due to lower smoking rates. This study suggests that the effects of paternal smoking on attentional control in children with ADHD should be considered a proxy for ADHD and/or smoking risk genes. Future studies should examine if the results can be generalized to other cognitive domains

Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.</p> <p>Methods</p> <p>We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis.</p> <p>Results</p> <p>Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to make up a rather more heterogeneous group with more severe information processing and attentional deficits.</p> <p>Conclusions</p> <p>Our findings are suggestive of a slowing of information processing for MS patients that may be a consequence of demyelination and axonal degeneration, which also seems to occur in MS patients that show little or no progression in the physical severity of the disease over time.</p

Response time variability and response inhibition predict affective problems in adolescent girls, not in boys: the TRAILS study

The present study examines the relationship between neurocognitive functioning and affective problems through adolescence, in a cross-sectional and longitudinal perspective. Baseline response speed, response speed variability, response inhibition, attentional flexibility and working memory were assessed in a cohort of 2,179 adolescents (age 10–12 years) from the TRacking Adolescents’ Individual Lives Survey (TRAILS). Affective problems were measured with the DSM-oriented Affective Problems scale of the Youth Self Report at wave 1 (baseline assessment), wave 2 (after 2.5 years) and wave 3 (after 5 years). Cross-sectionally, baseline response speed, response time variability, response inhibition and working memory were associated with baseline affective problems in girls, but not in boys. Longitudinally, enhanced response time variability predicted affective problems after 2.5 and 5 years in girls, but not in boys. Decreased response inhibition predicted affective problems after 5 years follow-up in girls, and again not in boys. The results are discussed in light of recent insights in gender differences in adolescence and state–trait issues in depression