Long-Term Effects of an Oligoantigenic Diet in Children with Attention-Deficit/Hyperactivity Disorder (ADHD) on Core Symptomatology.

In the early 1920s, it was discovered that nutrition is associated with what is known today as Attention-Deficit/Hyperactivity Disorder (ADHD) and that certain foods can worsen the symptoms. In previous studies, approximately 60% of the participants experience at least a 40% reduction in ADHD symptoms after an oligoantigenic diet (OD). The purpose of this study was to evaluate ADHD symptoms in children approximately 3.5 years after completing a 4-week oligoantigenic diet. Among 28 participants who completed the 4-week diet, 21 were re-assessed for this study after 3.5 years. The severity of ADHD symptoms was assessed with the ADHD-Rating-Scale-IV (ARS). Of 21 participants, 14 fulfilled the responder criterion, whereas 7 did not. At follow-up, 28% of the participants were taking medication. The mean ARS total score improved significantly from T1: M = 29.62 (SD = 9.80) to T2: M = 15.86 (SD = 8.56) between the time points before and after the diet (d = -1.91). There was also a lower ARS total score at the follow-up T5: M = 16.00 (SD = 10.52) compared to before the diet (d = -1.17). This study shows that individually adjusted nutrition significantly improved the ADHD symptomatology of the participants long-term. This suggests that an oligoantigenic diet with subsequent individual nutritional recommendations could become an additional treatment option for children with ADHD.

Individual Behavioral Reactions in the Context of Food Sensitivities in Children with Attention-Deficit/Hyperactivity Disorder before and after an Oligoantigenic Diet.

The influence of food intake on behavior problems of children with Attention-Deficit/Hyperactivity Disorder (ADHD) was already described in the early 20th century. Eliminating food components by using the Oligoantigenic Diet (OD) leads to reduction of ADHD symptoms for more than two-thirds of patients. The aim of our study was to reveal how to identify foods having an impact on ADHD symptomatology. Therefore, 28 children with ADHD participating in this uncontrolled, open trial were examined before and after a restricted elimination diet. They kept a daily 24-h recall nutrition and behavior journal and filled out the abbreviated Conners' scale (ACS) to identify foods which increased ADHD symptoms. The study was completed by 16 children (13 m/3 f). After four weeks of elimination diet the individual food sensitivities were identified in a reintroduction phase. A repetitive increase of ADHD symptoms by at least two points in ACS after food introduction hints at food sensitivity. Twenty-seven food sensitivity reactions were identified. Most of the participants were sensitive to more than one food. Food intolerances could not be identified without preceding OD. The combination of OD and subsequent food challenge appears as a valid method to identify individual food sensitivity in ADHD.

Preliminary Evaluation of the FETASS Training for Parents of Children With Autism Spectrum Disorder: A Pilot Study.

While several recent evaluation studies have shown the efficacy of parent training programs for children with neurodevelopmental disorders, manual-based training in German is still scarce. To address this gap, we developed a specific modularized training program for parents of children from preschool to pre-adolescent age with Autism Spectrum Disorder (FETASS). The overarching purpose of the FETASS intervention is to enhance social communication behavior and quality of life of the child by coaching parents. As a proximal target, the FETASS training aims to provide families with behavior management and communication strategies. The development of the training was influenced by published behavioral parent trainings and autism-specific interventions. The training comprises eight weekly sessions and targets families whose children have a diagnosis of Autism Spectrum Disorder (ASD) without intellectual and language impairments. As a preliminary pilot study, the purpose was to evaluate the acceptability of the training. Furthermore, the study aimed at initially evaluating social communication behavior, quality of life of the child, parental stress level, and parenting after training in comparison to a treatment as usual (TAU) group. Exploratively, long-term effects were investigated after 6 months of training as well. In total, 57 families participated (n[TAU] = 29, n[FETASS] = 28). Questionnaires about social communication behavior and quality of life of the child, parental stress, and parenting were administered at three time points (t1: baseline TAU/FETASS, t2: post TAU/FETASS; and t3: 6-month follow-up after FETASS). Primary outcome measures were the social communication behavior of the child and the parent's proxy report on quality of life of the child. Secondary outcome measures were changes in parental stress and parenting behavior. Acceptability of the training was very high and we had almost no dropouts during training. Results for the primary outcome measure of social communication behavior, overall quality of life of the child, and long-term effects on social communication behavior were not significant. While long-term findings for parent stress reduction and for the quality of life of the child are promising, further research has to be done in a future randomized controlled trial.

ADOS-Eye-Tracking: The Archimedean Point of View and Its Absence in Autism Spectrum Conditions.

Face perception and emotion categorization are widely investigated under laboratory conditions that are devoid of real social interaction. Using mobile eye-tracking glasses in a standardized diagnostic setting while applying the Autism Diagnostic Observation Schedule (ADOS-2), we had the opportunity to record gaze behavior of children and adolescents with and without Autism Spectrum Conditions (ASCs) during social interaction. The objective was to investigate differences in eye-gaze behavior between three groups of children and adolescents either (1) with ASC or (2) with unconfirmed diagnosis of ASC or (3) with neurotypical development (NTD) during social interaction with an adult interviewer in a diagnostic standard situation using the ADOS-2. In a case control study, we used mobile eye-tracking glasses in an ecologically valid and highly standardized diagnostic interview to investigate suspected cases of ASC. After completion of the ASC diagnostic gold standard including the ADOS-2, the participants were assigned to two groups based on their diagnosis (ASC vs. non-ASC) and compared with a matched group of neurotypically developed controls. The primary outcome measure is the percentage of total dwell times assessed for different areas of interest (AOI) with regard to the face and body of a diagnostic interviewer and the surrounding space. Overall, 65 children and adolescents within an age range of 8.3-17.9 years were included in the study. The data revealed significant group differences, especially in the central-face area. Previous investigations under laboratory conditions gave preferential attention to the eye region during face perception to describe differences between ASC and NTD. In this study - using an ecologically valid setting within a standard diagnostic procedure - the results indicate that neurotypically developed controls seem to process faces and facial expressions in a holistic manner originating from the central-face region. Conversely, participants on the Autism Spectrum (tAS) seem to avoid the central-face region and show unsystematic gaze behavior, not using the preferred landing position in the central-face region as the Archimedean point of face perception. This study uses a new approach, and it will be important to replicate these preliminary findings in future research.

Oligoantigenic Diet Improves Children's ADHD Rating Scale Scores Reliably in Added Video-Rating.

OBJECTIVES: The influence of food intake on behavioural disorders was already described in the early 20th century. Elimination of individually allergenic food items from individual diets ["oligoantigenic diet" (OD)] showed promise to improve attention-deficit/hyperactivity disorder (ADHD) symptoms. However, only few of the positive results were evaluated by blinded symptom rating. Therefore the present study's purpose was to evaluate the reliability of a non-blinded rating of the ADHD Rating Scale IV (ARS) for the assessment of OD effects in comparison to a blinded rating of the ARS based on pseudonymized video recordings. METHODS: Ten children (8m/2f) aged 8 to 14 with ADHD according to ICD-10 participated in an uncontrolled, open-label dietary intervention study. Food items, commonly related to intolerances, were eliminated for four weeks. Participants with > 40% improvement in the ARS between T1 (before the diet) and T2 (after the diet) were defined as responders. Nutrients with individual relevance to ADHD symptoms were identified in a following reintroduction phase (T3-T4) lasting 8-16 weeks. The ARS was completed by a non-blinded child and adolescent psychiatrist (T0-T4). Sessions were recorded on video, pseudonymized, and evaluated by three blinded raters. Complete data were captured for eight children. The inter-rater reliability between the non-blinded therapist and every blinded rater was determined by the intra-class correlation coefficient (ICC). Correlations according to Pearson and Spearman between the non-blinded and blinded rating were calculated for each rater. RESULTS: Two blinded raters and the non-blinded rater considered 5 of 8 (62.5%) children as responders, whereas one blinded rater disagreed as to the success of one case thus considering only 4 of 8 children as responders to the diet. Inter-rater reliability was assessed after each rater having scored 33 videos: The intra-class coefficients were >.9 for all raters (rater 1: ICC=.997, rater 2: ICC=.996, rater 3: ICC=.996) and the Spearman rho between the raters were high (n=33; rater 1: rho =.989, p<.0001, rater 2: rho=.987, p<.0001, rater 3: rho=.984, p<.0001), respectively. DISCUSSION: As both, blinded and non-blinded ratings of the ARS, revealed relevant significant improvement of ADHD scores in children following an OD in this uncontrolled trial, Randomized controlled trials appear as highly desirable in order to replicate these improvements and to establish reliable and unbiased effect sizes thereby fostering further more objective confirmatory measurements.

Psychometric analyses of the Tower of London planning task reveal high reliability and feasibility in typically developing children and child patients with ASD and ADHD.

The Tower of London (TOL) is probably the most often used assessment tool for planning ability in healthy and clinical samples. Various versions, including our proposed standard problem set, have proven to be feasible and reliable in adults. In contrast, reliability information for typically developing (TD) children and neurodevelopmental disorders during childhood are largely missing. Also, it would be highly desirable to attain a problem set that can be used across the whole lifespan. Therefore, here we examine reliability of our proposed standard problem set using a computerized TOL version in 178 TD children (two different samples), 49 children with high-functioning autism spectrum disorder (ASD) and 56 children with attention-deficit/hyperactivity disorder (ADHD) (age ranges of each group 6 to 13 years), and 130 young adults (age range 18 to 32 years). Greatest lower bound estimates of reliability were adequate to high in the two samples of TD children (.76 and .80) and high to very high in patients (ASD: .90; ADHD: .83). In young adults, all reliability indices were adequate to high. Moreover, a subset of four- and five-move problems exhibited sufficient performance variability and high part-whole correlations with the complete problem set in all samples. These findings demonstrate the reliability of the presented TOL problem set in both clinical and non-clinical child samples. A clinically feasible subset of four- and five-move problems is reflective of overall planning performance at all ages, hence enabling comparisons of planning ability within and between developmental samples across almost the whole lifespan.

Intuitive Moral Reasoning in High-Functioning Autism Spectrum Disorder: A Matter of Social Schemas?

Using a schema-theoretical perspective in the field of moral cognition, we assessed response behavior of adolescent (n = 15) and adult (n = 22) individuals with Autism Spectrum Disorder (ASD) in comparison with adolescent (n = 22) and adult (n = 22) neurotypically developed controls. We conceptualized the Intuitive Moral Reasoning Test-in five moral dilemmas, participants had to choose between two alternative actions and assess their decision with respect to emotional valence, arousal, moral acceptability and permissibility from both the perspective of the acting person and then of the victim. Patients with ASD displayed a different decision and response behavior, particularly when the dilemmas were based on extreme life situations in combination with a social schema involving close social relationships.

Inferior Frontal Gyrus Volume Loss Distinguishes Between Autism and (Comorbid) Attention-Deficit/Hyperactivity Disorder-A FreeSurfer Analysis in Children.

Objective: Autism spectrum (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with a high rate of comorbidity. To date, diagnosis is based on clinical presentation and distinct reliable biomarkers have been identified neither for ASD nor ADHD. Most previous neuroimaging studies investigated ASD and ADHD separately. Method: To address the question of structural brain differences between ASD and ADHD, we performed FreeSurfer analysis in a sample of children with ADHD (n = 30), with high-functioning ASD (n = 14), with comorbid high-functioning ASD and ADHD (n = 15), and of typically developed controls (TD; n = 36). With FreeSurfer, an automated brain imaging processing and analyzing suite, we reconstructed the cerebral cortex and calculated gray matter volumes as well as cortical surface parameters in terms of cortical thickness and mean curvature. Results: A significant main effect of the factor ADHD was detected for the left inferior frontal gyrus (Pars orbitalis) volume, with the ADHD group exhibiting smaller Pars orbitalis volumes. Dimensional measures of autism (SRS total raw score) and ADHD (DISYPS-II FBB-ADHD score) had no significant influence on the left Pars orbitalis volume. Both, ASD and ADHD tended to have an effect on cortical thickness or mean curvature, which did not survive correction for multiple comparisons. Conclusion: Our results underline that ADHD rather than ASD is associated with volume loss in the left inferior frontal gyrus (Pars orbitalis). This area might play a relevant role in modulating symptoms of inattention and/or impulsivity in ADHD. The effect of comorbid ADHD in ASD samples and vice versa, on cortical thickness and mean curvature, requires further investigation in larger samples.

Interindividual and Intraindividual Variation of Methylphenidate Concentrations in Serum and Saliva of Patients With Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Therapeutic drug monitoring is becoming increasingly important in psychiatric therapy, especially in children. However, for several reasons, it cannot yet be implemented as a daily routine in clinical or outpatient settings. To evaluate new, noninvasive procedures, blood and saliva (oral fluid) samples were collected from patients with attention-deficit/hyperactivity disorder (ADHD) who were also being administered methylphenidate (MPH). The study's main purposes were to correlate MPH concentrations in serum and saliva between subjects and to analyze intraindividual variation of serum concentration. METHODS: Thirty-six patients with ADHD (27 children and 9 adults) on MPH medication were included for drug analysis. MPH and its major metabolite ritalinic acid were quantified using liquid chromatography-tandem mass spectrometry measurements. The following correlations were investigated: (1) between drug concentrations in serum and saliva, and (2) between pH value and saliva to serum concentration ratio. Furthermore, the mean intraindividual MPH-concentration fluctuation in saliva under constant frame conditions was analyzed. RESULTS: After quantification, MPH concentrations were approximately 5 times higher in the saliva than in the serum, whereas the concentrations of ritalinic acid were much lower in saliva. We found significant correlations between concentrations of MPH in serum and saliva (r = 0.51, P < 0.05). Saliva MPH measures, compared with serum, were pH-dependent (r = -0.56, P < 0.01). Daily coefficient of variance of saliva concentration in children taking constant medication was 27.3% (11%-42%), whereas the coefficient of variance for the ratio of saliva to serum was 122% (2%-2060%). CONCLUSIONS: Our data indicate that the interindividual variation in saliva to serum concentrations is rather high, whereas the intraindividual variation is fairly low, as already shown in the literature for repeated citalopram serum measurements. Saliva may well serve as an alternative matrix for therapeutic drug monitoring of MPH in patients with ADHD, especially for follow-up examinations. Future research should focus on analyzing the relationship between drug levels in saliva and clinical effects as well as on understanding the mechanisms that generate saliva drug concentrations. These are essential steps before potential clinical use.

What Difference Does It Make? Implicit, Explicit and Complex Social Cognition in Autism Spectrum Disorders.

We tested social cognition abilities of adolescents with autism spectrum disorders (ASD) and neurotypically developed peers (NTD). A multi-faceted test-battery including facial emotion categorization (FEC), classical false belief tasks (FBT), and complex social cognition (SC), yielded significantly lower accuracy rates for FEC and complex SC tasks in ASD, but no significant differences in performance concerning FBT. A significant correlation between age and performance in a FEC task and in a complex task was found only in ASD. We propose that dynamic and/or fragmented FEC tasks can elicit deficits in implicit processing of facial emotion more efficiently. The difficulties of ASD in solving complex SC tasks can be ascribed to deficits in the acquisition and application of social schemata.

Development of Planning in Children with High-Functioning Autism Spectrum Disorders and/or Attention Deficit/Hyperactivity Disorder.

Planning impairment is often observed in children with high-functioning autism spectrum disorders (ASD), but attempts to differentiate planning in ASD from children with attention deficit hyperactivity disorder (ADHD) and typically developing children (TD) have yielded inconsistent results. This study examined differences between these groups by focusing on development and analyzing performance in searching ahead several steps ("search depth") in addition to commonly used global performance measures in planning. A cross-sectional consecutive sample of 83 male patients (6-13 years), subgrouped as ASD without (ASD-, n = 18) or with comorbid ADHD (ASD+, n = 23), ADHD only (n = 42) and n = 42 TD children (6-13 years) were tested with the Tower-of-London-task. For global performance, ASD+ showed the lowest accuracy in younger children, but similar performance as TD at older ages, suggesting delayed development. Typically, a prolongation of planning time with increasing problem difficulty is observed in older children as compared to younger children. Here, this was most pronounced in ASD-, but under-expressed in ADHD. In contrast to global performance, effects of search depth were independent of age. ASD-, but not ASD+, showed increased susceptibility to raised demands on mentally searching ahead, along with the longest planning times. Thus, examining both global and search depth performance across ages revealed discernible patterns of planning between groups. Notably, the potentially detrimental impact of two diagnosed disorders does not add up in ASD+ in this task. Rather, our results suggest paradoxical enhancement of performance, ostensibly attributable to disruption of behavioral rigidity through increased impulsivity, which did not take place in ASD-. Autism Res 2016, 9: 739-751. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Identification of neuromotor deficits common to autism spectrum disorder and attention deficit/hyperactivity disorder, and imitation deficits specific to autism spectrum disorder.

Deficits in motor and imitation abilities are a core finding in autism spectrum disorders (ASD), but impaired motor functions are also found in attention deficit/hyperactivity disorder (ADHD). Given recent theorising about potential aetiological overlap between the two disorders, the present study aimed to assess difficulties in motor performance and imitation of facial movements and meaningless gestures in a sample of 24 ADHD patients, 22 patients with ASD, and 20 typically developing children, matched for age (6-13 years) and similar in IQ (>80). Furthermore, we explored the impact of comorbid ADHD symptoms on motor and imitation performance in the ASD sample and the interrelationships between the two groups of variables in the clinical groups separately. The results show motor dysfunction was common to both disorders, but imitation deficits were specific to ASD. Together with the pattern of interrelated motor and imitation abilities, which we found exclusively in the ASD group, our findings suggest complex phenotypic, and possibly aetiological, relationships between the two neurodevelopmental conditions.

Looking ahead from age 6 to 13: a deeper insight into the development of planning ability.

Planning ability gradually increases throughout childhood. However, it remains unknown whether this is attributable to global factors such as an increased ability and willingness to inhibit premature, impulsive responding, or due to the availability of specific planning operations, such as being able to mentally plan ahead more steps ('search depth') or to derive a clear temporal order of goals by the task layout ('goal hierarchy'). Here, we studied the development of planning ability with respect to these global and problem-specific aspects (search depth and goal hierarchy) of performance in 178 children from 6 to 13 years using the Tower of London task. As expected, global performance gradually developed with age. In accordance, planning durations increasingly reflected global problem demands with longer pre-planning in harder problems. Furthermore, specific planning parameters revealed that children were increasingly capable of mentally searching ahead more steps. In contrast, the ability to derive a goal hierarchy did not show age-related changes. While the global development of planning performance and adaptive planning durations were proposed to primarily reflect enhanced self-monitoring, the specific increase in search depth across childhood that most likely proceeds until young adult age represents more directly planning-related processes. Thus, development of planning ability is supported by multiple contributions.

Are There Any Connections between Language Deficits and Cognitive Slowing in Alzheimer's Disease?

BACKGROUND: Speech disorders already occur in the early phases of Alzheimer's disease (AD). As a possible cause, problems of executive processes are discussed. Cognitive slowing is also repeatedly addressed. AIMS: Are there any connections between cognitive slowing and speech disorders in AD? And is there a relationship between cognitive slowing and executive processes? METHODS: The data of 72 healthy controls and 52 AD patients were examined with regard to their language performance and their response times in a computerized Stroop paradigm. RESULTS: The AD patients showed significantly worse results in all language tests as well as much longer reaction times in all Stroop conditions, especially in the interference condition (Stroop 3). Speech errors and response times correlated with severity (MMSE), and the speech errors correlated with the reaction times in Stroop 3 (interference condition, which reflects the processing time of executive processes). CONCLUSION: The most interesting question now is: How are language processing and executive processing time (Stroop 3) related?

Deficits in motor abilities and developmental fractionation of imitation performance in high-functioning autism spectrum disorders.

The co-occurrence of motor and imitation disabilities often characterises the spectrum of deficits seen in patients with autism spectrum disorders (ASD). Whether these seemingly separate deficits are inter-related and whether, in particular, motor deficits contribute to the expression of imitation deficits is the topic of the present study and was investigated by comparing these deficits' cross-sectional developmental trajectories. To that end, different components of motor performance assessed in the Zurich Neuromotor Assessment and imitation abilities for facial movements and non-meaningful gestures were tested in 70 subjects (aged 6-29 years), including 36 patients with high-functioning ASD and 34 age-matched typically developed (TD) participants. The results show robust deficits in probands with ASD in timed motor performance and in the quality of movement, which are all independent of age, with one exception. Only diadochokinesis improves moderately with increasing age in ASD probands. Imitation of facial movements and of non-meaningful hand, finger, hand finger gestures not related to social context or tool use is also impaired in ASD subjects, but in contrast to motor performance this deficit overall improves with age. A general imitation factor, extracted from the highly inter-correlated imitation tests, is differentially correlated with components of neuromotor performance in ASD and TD participants. By developmentally fractionating developmentally stable motor deficits from developmentally dynamic imitation deficits, we infer that imitation deficits are primarily cognitive in nature.

On the temporal characteristics of performance variability in attention deficit hyperactivity disorder (ADHD).

Increased intra-subject variability of reaction times (ISV-RT) is one of the most consistent findings in attention-deficit/hyperactivity disorder (ADHD). Although the nature of this phenomenon is still unclear, it has been hypothesised to reflect interference from the Default Mode Network (DMN). So far, ISV-RT has been operationally defined either as a frequency spectrum of the underlying RT time series, or as a measure of dispersion of the RT scores distribution. Here, we use a novel RT analysis framework to link these hitherto unconnected facets of ISV-RT by determining the sensitivity of different measures of RT dispersion to the frequency content of the underlying RT time series. N=27 patients with ADHD and N=26 healthy controls performed several visual N-back tasks. Different measures of RT dispersion were repeatedly modelled after individual frequency bands of the underlying RT time series had been either extracted or suppressed using frequency-domain filtering. We found that the intra-subject standard deviation of RT preserves the "1/f noise" characteristic typical of human RT data. Furthermore and most importantly, we found that the ex-Gaussian parameter τ is rather exclusively sensitive to frequencies below 0.025 Hz in the underlying RT time series and that the particularly slow RTs, which nourish τ, occur regularly as part of an quasi-periodic, ultra-slow RT fluctuation. Overall, our results are compatible with the idea that ISV-RT is modulated by an endogenous, slowly fluctuating process that may reflect DMN interference.

Diurnal variation of phenylalanine and tyrosine concentrations in adult patients with phenylketonuria: subcutaneous microdialysis is no adequate tool for the determination of amino acid concentrations.

BACKGROUND: Metabolic control and dietary management of patients with phenylketonuria (PKU) are based on single blood samples obtained at variable intervals. Sampling conditions are often not well-specified and intermittent variation of phenylalanine concentrations between two measurements remains unknown. We determined phenylalanine and tyrosine concentrations in blood over 24 hours. Additionally, the impact of food intake and physical exercise on phenylalanine and tyrosine concentrations was examined. Subcutaneous microdialysis was evaluated as a tool for monitoring phenylalanine and tyrosine concentrations in PKU patients. METHODS: Phenylalanine and tyrosine concentrations of eight adult patients with PKU were determined at 60 minute intervals in serum, dried blood and subcutaneous microdialysate and additionally every 30 minutes postprandially in subcutaneous microdialysate. During the study period of 24 hours individually tailored meals with defined phenylalanine and tyrosine contents were served at fixed times and 20 min bicycle-ergometry was performed. RESULTS: Serum phenylalanine concentrations showed only minor variations while tyrosine concentrations varied significantly more over the 24-hour period. Food intake within the patients' individual diet had no consistent effect on the mean phenylalanine concentration but the tyrosine concentration increased up to 300% individually. Mean phenylalanine concentration remained stable after short-term bicycle-exercise whereas mean tyrosine concentration declined significantly. Phenylalanine and tyrosine concentrations in dried blood were significantly lower than serum concentrations. No close correlation has been found between serum and microdialysis fluid for phenylalanine and tyrosine concentrations. CONCLUSIONS: Slight diurnal variation of phenylalanine concentrations in serum implicates that a single blood sample does reliably reflect the metabolic control in this group of adult patients. Phenylalanine concentrations determined by subcutaneous microdialysis do not correlate with the patients' phenylalanine concentrations in serum/blood.

Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome.

AIM: We aimed to investigate the induction of long-term potentiation (LTP)-like plasticity by paired associative stimulation (PAS) in patients with high-functioning autism and Asperger syndrome (HFA/AS). METHOD: PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS(25)) was performed in patients with HFA/AS (n=9; eight males, one female; mean age 17 y 11 mo, SD 4 y 5 mo) and in typically developing age-matched volunteers (n=9; five males, four females; mean age 22 y 4 mo, SD 5 y 2 mo). The amplitude of motor-evoked potentials was measured before PAS(25), immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PAS(N20+2)) was performed in six additional patients with HFA/AS. Short-interval intracortical inhibition was measured using paired-pulse stimulation. RESULTS: In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor-evoked potentials after PAS(25). This finding could also be demonstrated after adaptation for N20 latency. Short-interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect. INTERPRETATION: Our results show a significant impairment of LTP-like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP-like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory-motor integration in these patients.

Patterns of change in ocular motor development.

This study examined development of pro- and anti-saccadic eye movements in a cross-sequential research design. A hundred and seventeen subjects aged 6-18 years at initial testing were retested 18.9 ± 1.2 months later. Pro- and anti-saccades were elicited under the gap and overlap conditions. We found strong longitudinal developmental effects on all parameters analysed, in particular those derived from the anti-saccade task. These longitudinal changes structurally resembled the cross-sectional age effects observed for the same data. However, the principal component analyses of longitudinal "true" and raw difference scores revealed a stable three-factor solution that was robust to age effects and included (a) an express saccade factor, (b) a variability factor and (c) a factor consisting of direction errors with regular latencies and pro-saccadic RT. Cross-sectional factor analysis, by contrast, merged these two last-mentioned factors. We thus conclude that longitudinal data can provide unique information regarding individual differences in the patterns of developmental change.

Cognitive correlates of anti-saccade task performance.

The anti-saccade task (AST) is widely used in experimental, clinical, and neuroscience research as a pronounced test of executive functions. AST research includes to some extent also the investigation into its cognitive correlates. In the present study, we have examined cognitive correlates of the AST in the short-term/working memory, executive functions, and intelligence domains in healthy adults. We have obtained the following results. In line with previous research, the global percentage of direction errors PDE comprised of two only negligibly correlated components, direction errors with express or regular latencies. Substantial correlations with the other cognitive measures were obtained only for regular direction errors and, less so, for the global PDE. Results add to the evidence that distinguishes express and regular direction errors and underline that the complex requirements of the AST are reflected in a comparatively rich set of non-redundant parameters.