ABBREVIATIONS ASDAutism spectrum disorder GABA 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 17y 11mo, SD 4y 5mo) and in typically developing age-matched volunteers (n=9; five males, four females; mean age 22y 4mo, SD 5y 2mo). 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.Autism spectrum disorders (ASDs) are severe neurodevelopmental disorders characterized by a qualitative impairment of social interaction and communication, repetitive stereotyped patterns of behaviour, and restricted interests and activities. These are accompanied by gross and fine motor impairment in both high-functioning autism (HFA) and Asperger syndrome. [2][3][4] Motor impairments range from unspecific 'clumsiness' to Parkinsonian-like movement patterns, indicating an involvement of the central nervous structures responsible for intact motor behaviour and motor learning. 5,6 Strengthening of synaptic connections by long-term potentiation (LTP) in animals and LTP-like plasticity in humans has been shown to be a basic mechanism of motor learning. 7,8 LTP deficits in animal models of autism were recently identified. Mice with mutations in the methyl CpG binding protein 2 (MECP2) show impaired LTP induction and deficits in learning and memory. 9,10 In humans, MECP2 mutations cause Rett syndrome, and reduced expression of MECP2 in the frontal lobe cortex has been described in patients with ASD.11 MECP2 protein regulates the transcription of the gene encoding for brain-derived neurotrophic factor, which is strongly involved in induction of LTP-like plasticity.12 A reduced excitatory synaptic connectivity in MECP2 knockout mice precedes deficits in neuronal plasticity. 9 It has also been demonstrated that a dysfunction in c-aminobutyric acid (GABA) signalling mediates autism-like stereotypies 13 and ...

Whether or not a formal approach to spatial relations is a cognitively adequate (the term will be explicated in this paper) model of human spatial knowledge is more often based on the intuition of the researchers than on empirical data In contrast, the research reported here is concerned with an empirical assessment of one of the three general classes of spatial relations, namely topological knowledge. In the reported empirical investigation, subjects had to group numerous spatial configurations consisting of two circles with respect to their similarity. As is well known, such tasks are solved on the basis of underlying spatial concepts. The results were compared with the RCC-theory and Egenhofer‘s approach to topological relations and support the assumption that both theories are cognitively adequate in a number of important aspects

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.

The aim of this study was to evaluate long-term weight gain associated with clozapine, olanzapine, and risperidone treatment and its clinical risk factors in children and adolescents. At four child and adolescent psychiatric departments, the weight and body mass index of initially hospitalized patients (aged 9.0-21.3 years) treated with clozapine (n = 15), olanzapine (n = 8), and risperidone (n = 10) were prospectively monitored for 45 weeks. Clinical risk factors (age, gender, baseline weight, dosage, drug-naivety) were tested for their association with weight gain in the three groups. All three groups experienced significant weight gain between baseline and endpoint. The absolute and percentage average weight gains were significantly higher for the olanzapine group (16.2 +/- 8.8 kg; 30.1 +/- 18.9%) than for the clozapine (9.5 +/- 10.4 kg; 14.8 +/- 15.8%) and the risperidone (7.2 +/- 5.3 kg; 11.5 +/- 6.0%) groups. Olanzapine is associated with extreme long-term weight gain in children and adolescents that, in addition, is much higher than that expected in adults. Clozapine and risperidone are associated with a less marked weight gain in children and adolescents but also much higher than that expected in adults. These differences may affect compliance with medication and health risk.

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.