Robert Licht

Sustained attention and inhibition of cognitive interference in treated phenylketonuria: associations with concurrent and lifetime phenylalanine concentrations

Fifty-seven 7-14-year-old early- and continuously treated phenylketonuria (PKU) patients and 65 matched controls performed a sustained attention task. PKU patients with plasma phenylalanine (phe) levels higher than 360 micromol/l at the time of testing exhibited, compared to controls, lower speed of information processing, a lower ability to inhibit task-induced cognitive interference, less consistent performance, and a stronger decrease of performance level over time. Patients with concurrent phe levels lower than 360 micromol/l did not differ from controls and were significantly better than patients with levels higher than 360 micromol/l. Strong relationships were found with task performance for phe levels during the pre-school years and between ages 5 and 7. These correlations were stronger than those between concurrent phe level and task performance. Significant multiple regression models were found with age accounting for the largest proportion of variance of tempo and tempo fluctuation, and lifetime phe levels (particularly phe level between ages 5 and 7) accounting for the largest proportion of variance of the relative number of inhibition errors and its increase over time. Phe level between ages 5 and 7 also contributed significantly to the variance of tempo and tempo fluctuation. Neuropsychological outcome was independent of IQ. The results indicate that strict dietary adherence during these periods is beneficial to attentional control later in life. We suggest that phe levels should be maintained under 360 micromol/l until approximately age 12, when development of attentional control approaches an adult level.

Inhibition of prepotent responding and attentional flexibility in treated phenylketonuria

Inhibition of prepotent responding and attentional flexibility were assessed in 58 early and continuously treated phenylketonuria (PKU) patients and 69 controls, age 7 to 14 years. A computerized task was used requiring participants to process consecutive stimuli according to various attentional sets. Analysis of error rate suggested poorer inhibition of prepotent responding in PKU patients compared with controls. No influence of concurrent plasma phenylalanine (phe) was shown, neither in the younger (age < 11 years) nor in the older participants (age sup3; 11 years). Analysis of error rate provided strong evidence for poorer attentional flexibility in PKU patients compared with controls. The difference between attentional flexibility in controls and PKU patients could mainly be attributed to younger PKU patients, with concurrent phe levels higher than 360μmol/L.Younger PKU patients with phe levels below 360 μmol/L performed at the same level as age-matched controls. Performance of PKU patients was strongly associated with phe levels in age periods during the first 10 years of life, which are characterized by a strong development of executive functioning (ages 2-7 and age 9). High phe levels during these age periods could delay development of inhibitory control and attentional flexibility. With regard to treatment, analyses with lifetime and concurrent phe levels support strict dietary control throughout the first decade of life, after which the phe-restricted diet can be relaxed. However, based on the evidence that development of specific executive functions continues until approximately age 12, it is recommended to maintain phe levels below 360 μmol/L throughout early adolescence.

The development of lateral event-related potentials (ERPs) related to word naming: A four year longitudinal study.

Event-related potentials (ERPs) were recorded from the left and right temporal and parietal sites during a word naming task. Subjects were a group of children that were followed over four consecutive years starting at Kindergarten. ERP waveforms contained a sequence of positive and negative components (N150, P240, N360, N530 and SW). All components, except N150, showed changes in amplitude as a function of age, whereas SW, N360 and N150 also changed in hemispheric distribution. In addition, a relationship was found between reading performance and ERP amplitudes over the right parietal hemisphere in young children, and over the left temporal hemisphere in older children. Proficient readers showed larger (more negative) parietal N530 amplitudes than less proficient readers, especially when stimuli were degraded words. The results are discussed in terms of age-related changes in right and left hemisphere functions involved in early and advanced stages of reading, that might possibly be related to visual word recognition.

Motor function under lower and higher controlled processing demands in early and continuously treated phenylketonuria

This study examined motor control in 61 early and continuously treated patients with phenylketonuria (PKU) and 69 control participants, aged 7 to 14 years. The pursuit task demanded concurrent planning and execution of unpredictable movements, whereas the tracking task required a highly automated circular movement that could be planned in advance. PKU patients showed significantly poorer motor control in both tasks compared with control participants. Deficits were particularly observed for younger patients (age < 11 years). Differences between control participants and PKU patients were significantly greater in the pursuit task compared with the tracking task, indicating more serious deficits when a higher level of controlled processing is required. Correlations with historical phenylalanine levels indicated a later maturation of the level of control required by the pursuit task compared with the tracking task.

Cortical responses to word reading by right- and left-eared normal and reading disturbed children.

Abstract There is behavioral evidence that children showing left ear dominance (LED) generate hemispheric reading strategies which are different from those who show right ear dominance (RED) subsequent to dichotic verbal stimulation. Electrophysiological evidence of this was sought in the present investigation. Normal and reading-disturbed children were required to read monosyllabic words that were flashed at the point of fixation. Event-related potentials (ERP) were analysed in relation to reading level (normal vs disturbed readers), ear dominance (LED vs RED), and side of diversion (left temporal vs right temporal and left parietal vs right parietal). Significant interactions were found for P310 and N440 amplitudes and latencies, indicating that normal and reading-disturbed LED and RED children generate different reading strategies.

Short-term dietary interventions in children and adolescents with treated phenylketonuria: Effects on neuropsychological outcome of a well-controlled population

This study addressed two questions: is there an effect of dietary interventions that induce relatively small changes in phenylalanine (Phe) concentration on neuropsychological outcome of early- and continuously treated phenylketonuria (PKU) patients, and are there differences in effects for PKU children and adolescents? To answer the first question, the effect of a short-term dietary intervention (1–2 weeks) was compared for patients whose Phe concentrations increased vs those whose Phe concentrations decreased. Controls were tested twice to control for learning effects. To answer the second question, the effect of dietary interventions was examined in younger patients (aged 7–10 years) and older patients (aged 11–14 years). The effect of dietary interventions was determined with three neuropsychological tasks: one requiring sustained attention; a second demanding maintenance in working memory; and a third in which complex operations were performed in working memory. Relatively small fluctuations in Phe concentration were found to influence neuropsychological task performance of PKU patients. Patients whose Phe concentrations decreased at the second assessment showed generally more improvement than controls. Patients whose Phe concentrations had increased showed minimal improvement or deterioration of task performance. The strongest effects were observed when sustained attention and manipulation of working memory content were required. There were some indications of a greater sensitivity of younger patients to fluctuations in Phe concentration.

Grade-related changes in event-related potentials (ERPs) in primary school children: Differences between two reading tasks.

Event-related potentials (ERPs) were recorded from the left and right temporal and parietal sites during word reading in a group of children who were followed over three consecutive years, starting at Grade 1. The first task required the child to read repeatedly presented words; the second task consisted of a series of different words, with each word being presented only once. All ERP components showed changes in amplitude as a function of grade: P240, N530, the parietal N150, and SW all decreased, whereas the temporal N360 and SW both increased. In addition, SW changed from no asymmetry to larger positivity over the right site, whereas N360 changed from symmetric amplitudes to larger amplitudes over the left hemisphere with grade. Single word presentations were associated with smaller SW activity and larger N530 and N360 amplitudes than were repeated word presentations. It was also found that proficient readers showed larger SW and N360 asymmetries and shorter vocal response times than did less proficient readers. In addition, a positive relationship was found between reading performance and ERP amplitudes over the left temporal hemisphere at Grades 2 and 3, particularly in the single word reading task. The results are discussed in terms of age-related changes in right and left hemisphere functions involved in learning to read.

Hemispheric distribution of ERP components and word naming in preschool children.

Event-related potentials (ERPs) were recorded at the left and right temporal and parietal sites during a word-naming task in 61 children ranging in age from 5.1 to 6.2 years. Principal component analysis (PCA) was performed on the average ERP waveforms. Analyses of the factor scores revealed that the P240, N380, and SW components were asymmetrically distributed over the hemispheres. Fast reading acquisition was associated with smaller N380 and larger SW activity than slow reading acquisition. Multiple regression analyses indicated that only right hemispheric ERP components were significantly associated with rate of reading acquisition. These findings are discussed in terms of right hemispheric involvement in early reading acquisition.

Shifting of attention in subtyped dyslexic children: An event‐related potential study

The behavioral and electrophysiological correlates of the ability to shift attention was investigated in 9‐ to 12‐year‐old children, 22 L‐dyslexic, 21 P‐dys‐lexic, and 25 normal readers. L‐dyslexia presumably is associated with premature generation of left‐hemispheric reading strategies and P‐dyslexia is associated with the perseverant generation of right‐hemispheric strategies. Subjects were presented a task developed by Posner et al. that requires the covert shift of attention to a spatial location and a response to an imperative stimulus that appears in the cued or uncued visual field. In agreement with previous findings, valid information (coincidence of cue and stimulus) elicited faster reaction times and fewer errors than invalid information (non‐coincidence of cue and stimulus). Contrary to predictions neutral cues elicited the slowest and most accurate responses. No effect of group was found. Cue‐ and stimulus‐related event‐related potentials (ERPs) generally were pronounced over the right posteri...

Event-related potential correlates of selective processing in early- and continuously-treated children with phenylketonuria: effects of concurrent phenylalanine level and dietary control.

This study focused on important characteristics of attentional (selective) processing in children with early-treated phenylketonuria (PKU). Seven to 14-year-old children with PKU were allocated to high phenylalanine (Phe) and low Phe groups and compared with control children on amplitudes and latencies of early and late event-related potential (ERP) components elicited during a selective processing task. These components are thought to measure early sensory processes (stimulus encoding/perception) and later selection processes (target detection). The effects of concurrent Phe level and dietary control on brain activity and behavioural performance were studied. Results showed that children with PKU with high Phe levels were less accurate and made more false alarms than controls and children with PKU with low Phe levels. Both children with PKU and controls displayed the expected early fronto-central selection negativity and a late positive peak over posterior sites associated with sensory aspects of the selective attention task. However, in contrast with controls, children with PKU showed an absence of condition differences for selection positivity over anterior sites associated with target detection. Negative and positive selection potentials over fronto-central sites were dependent on concurrent and historical Phe levels, whereas sensory potentials depended more strongly on historical Phe levels. It is concluded that both sensory and selection aspects of attention are affected by Phe levels. The relative predictive strength of historical Phe levels suggests that high Phe levels during sensitive periods for brain maturation may have long-lasting influences on selective attention.