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Atypicalities in connectivity between brain regions have been implicated in a\ud range of neurocognitive disorders. We require metrics to assess stable individual\ud differences in connectivity in the developing brain, while facing the challenge of\ud limited data quality and quantity. Here, we examine how varying core processing\ud parameters can optimise the test-retest reliability of EEG connectivity measures\ud in infants.\ud EEG was recorded twice with a 1-week interval between sessions in 10-\ud month-olds. EEG alpha connectivity was measured across different epoch lengths\ud and numbers, with the phase lag index (PLI) and debiased weighted PLI\ud (dbWPLI), for both whole-head connectivity and graph theory metrics. We\ud calculated intra-class correlations between sessions for infants with sufficient\ud data for both sessions (N’s = 19 – 41, depending on the segmentation method).\ud Reliability for the whole brain dbWPLI was higher across many short\ud epochs, whereas reliability for the whole brain PLI was higher across fewer long\ud epochs. However, the PLI is confounded by the number of available segments.\ud Reliability was higher for whole brain connectivity than graph theory metrics.\ud Thus, segmenting available data into a high number of short epochs and\ud calculating the dbWPLI is most appropriate for characterising connectivity in\ud populations with limited availability of EEG data.

Infants’ socio-cognitive ability develops dramatically during the first year of life. From the perspective of ontogeny, the early development of social behavior allows for parent-child attachment, which in turn enhances survival. Thus, it is theorized that the development of social behavior, driven by social brain networks, forms the core of developmental acquisitions during this period. Further, understanding the maturation within the neural networks during social development is crucial to obtain a better grasp of the development of social developmental disorders. Therefore, we performed a longitudinal study in 854 infants measured at around 5 and 10 months to map the development of functional networks in the brain when infants were processing social and non-social videos. Using EEG, we focused on the frequency bands most commonly connected to social behavior: theta and alpha. We found that alpha networks remained relatively stable over the first year of life and showed no selectivity for social versus non-social stimuli, theta networks, showed strong global reconfigurations. The development of the theta networks progressed from a parietal occipital network in early infancy to a frontoparietal network towards the end of the first year of life. This reconfiguration coincided with selectivity for social versus non-social stimuli, with infants approaching the end of their first year of life showing increased synchronicity of theta communication when watching social videos versus non-social videos. Our findings provide strong evidence for the involvement of a frontoparietal theta network in the development of the social brain.

Face-to-face interaction is a primary mode of human social behavior which includes verbal and non-verbal expressions, e.g. speech, gazing, eye contact, facial displays, and gestures (Holler & Levinson, 2019). In this study, we investigated the relation between speech and gaze behavior during 'face-to-face' dialogues between parents and their preadolescent children (9-11 years). 79 child-parent dyads engaged in two semi-structured conversations about family-related topics. We used a state-of-the-art dual-eye tracking setup (Hessels et al. 2019) that is capable of concurrently recording eye movements, frontal video recordings, and audio from two conversational partners. Crucially, the setup is designed in such a way that eye contact can be maintained using half-silvered mirrors, as opposed to e.g. Skype where the camera is located above the screen. Parents and children conversed about two different topics for five minutes each, one 'conflict' (e.g. bedtime, homework) and one 'cooperation' (e.g. organize a party) topic. Preliminary analyses of speech behavior (Figure 1) show that children talked more in the cooperative task and talked less when discussing a topic of disagreement with their parents. Conversely, parents talked more during the conflict-task and less during the cooperative-task. The next step is to combine measures of speech and gaze to investigate the interplay and temporal characteristics of verbal and non-verbal behavior during face-to-face interactions.

Rapid decoding of emotional expressions is essential for social communication. Fast processing of facial expressions depends on the adequate (subcortical) processing of important global face cues in the low spatial frequency (LSF) ranges. However, children below 9 years of age extract fearful expression information from local details represented by high SF (HSF) image content. Our ERP study investigated at which developmental stage this ineffective HSF-driven processing is replaced by the proficient and rapid LSF-driven perception of fearful faces, in which adults are highly skilled. We examined behavioral and neural responses to high- and low-pass filtered faces with a fearful or neutral expression in groups of children on the verge of pre-adolescence (9-10 years), adolescents (14-15 years), and young adults (20-28 years). Our results suggest that the neural emotional face processing network has a protracted maturational course into adolescence, which is related to changes in SF processing. In mid-adolescence, increased sensitivity to emotional LSF cues is developed, which aids the fast and adequate processing of fearful expressions that might signal impending danger.

A long-standing hypothesis is that humans have a bias for fixating the eye region in the faces of others. Most studies have tested this hypothesis with static images or videos of faces, yet recent studies suggest that the use of such "nonresponsive" stimuli might overlook an influence of social context. The present study addressed whether the bias for fixating the eye region in faces would persist in a situation that allowed for social interaction. In Experiment 1, we demonstrate a setup in which a duo could engage in social interaction while their eye movements were recorded. Here, we show that there is a bias for fixating the eye region of a partner that is physically present. Moreover, we report that the time 1 partner in a duo spends looking at the eyes is a good predictor of how long the other partner looks at the eyes. In Experiment 2, we investigate whether participants attune to the level of eye contact instigated by a partner by having a confederate pose as one of the partners. The confederate was subsequently instructed to either fixate the eyes of the observer or scan the entire face. Gaze behaviour of the confederate did not affect gaze behaviour of the observers. We conclude that there is a bias to fixate the eyes when partners can engage in social interaction. In addition, the amount of time spent looking at the eyes is duo-dependent, but not easily manipulated by instructing the gaze behaviour of 1 partner. (PsycINFO Database Record

Face perception is characterized by configural processing, which depends on visual information in the low spatial frequency (LSF) ranges. However, it is unclear whether LSF content is equally important for face memory. The present study investigated how face information in the low and high SF range plays a role in the configural encoding of faces for short-term and long-term recall. Moreover, we examined how SF-dependent face memorization develops in female adolescence, by comparing children (9-10-year-olds), adolescents (12-13-year-olds and 15-16-year-olds), and young adults (21-32-year-olds). Results show that similar to face perception, delayed face recognition was consistently facilitated by LSF content. However, only adults were able to adequately employ configural LSF cues for short-term recall, analogous to the slow maturation of LSF-driven configural face perception reported by previous studies. Moreover, the insensitivity to face inversion of early adolescents revealed their inadequate use of configural face cues regardless of SF availability, corroborating previous reports on an adolescent "dip" in face recognition. Like face perception, face recognition has a protracted maturational course. In (female) adolescence, sensitivity to configural LSF cues is developed, which aids not only configural face perception but also face memorization.

Understanding the development of attention is key to understanding cognitive maturation. The gap-overlap task can be administered at all ages and is widely used to study the development of overt visual attention. However, studies using the gap-overlap task report different measures and little is known about the tasks’ psychometric properties, especially in infants. We tested the 1-week test–retest reliability of two frequently used gap-overlap measures of attentional disengagement in 10-month-old infants; the gap effect as measured by the difference between the gap and overlap condition and the gap effect as measured by the difference between the gap and baseline condition. Sixty-seven infants performed the gap-overlap task twice, of which 45 infants had sufficient data quality for further analyses. Test–retest reliability of the overlap-gap gap effect was higher (r = .50) than the baseline-gap gap effect (r = .29). Moreover, the shared variance between overlap and baseline saccadic reaction times was moderate to high across sessions. In light of these results and the methodological challenges and limitations of infant research, we consider the overlap-gap gap effect to be a good measure to study the development of attentional disengagement in infants and suggest the exclusion of the baseline condition in future studies.

A problem in eyetracking research is choosing areas of interest (AOIs): Researchers in the same field often use widely varying AOIs for similar stimuli, making cross-study comparisons difficult or even impossible. Subjective choices while choosing AOIs cause differences in AOI shape, size, and location. On the other hand, not many guidelines for constructing AOIs, or comparisons between AOI-production methods, are available. In the present study, we addressed this gap by comparing AOI-production methods in face stimuli, using data collected with infants and adults (with autism spectrum disorder [ASD] and matched controls). Specifically, we report that the attention-attracting and attention-maintaining capacities of AOIs differ between AOI-production methods, and that this matters for statistical comparisons in one of three groups investigated (the ASD group). In addition, we investigated the relation between AOI size and an AOI's attention-attracting and attention-maintaining capacities, as well as the consequences for statistical analyses, and report that adopting large AOIs solves the problem of statistical differences between the AOI methods. Finally, we tested AOI-production methods for their robustness to noise, and report that large AOIs-using the Voronoi tessellation method or the limited-radius Voronoi tessellation method with large radii-are most robust to noise. We conclude that large AOIs are a noise-robust solution in face stimuli and, when implemented using the Voronoi method, are the most objective of the researcher-defined AOIs. Adopting Voronoi AOIs in face-scanning research should allow better between-group and cross-study comparisons.

Eye-tracking research in infants and older children has gained a lot of momentum over the last decades. Although eye-tracking research in these participant groups has become easier with the advance of the remote eye-tracker, this often comes at the cost of poorer data quality than in research with well-trained adults (Hessels, Andersson, Hooge, Nystrom, & Kemner Infancy, 20, 601-633, 2015; Wass, Forssman, & Leppanen Infancy, 19, 427-460, 2014). Current fixation detection algorithms are not built for data from infants and young children. As a result, some researchers have even turned to hand correction of fixation detections (Saez de Urabain, Johnson, & Smith Behavior Research Methods, 47, 53-72, 2015). Here we introduce a fixation detection algorithm-identification by two-means clustering (I2MC)-built specifically for data across a wide range of noise levels and when periods of data loss may occur. We evaluated the I2MC algorithm against seven state-of-the-art event detection algorithms, and report that the I2MC algorithm's output is the most robust to high noise and data loss levels. The algorithm is automatic, works offline, and is suitable for eye-tracking data recorded with remote or tower-mounted eye-trackers using static stimuli. In addition to application of the I2MC algorithm in eye-tracking research with infants, school children, and certain patient groups, the I2MC algorithm also may be useful when the noise and data loss levels are markedly different between trials, participants, or time points (e.g., longitudinal research).

In the manuscript, we write that saccadic reaction time was determined as the time between the offset of the last fixation on the central stimulus and the onset of the peripheral stimulus (the target).

OBJECTIVE: In the current study, we investigated the role of noradrenaline in directing (bias) and disengagement of visuospatial attention. METHODS: We assessed the effect of clonidine on event-related brain potential (ERP) reflections of bias and disengagement in a double-blind placebo-controlled crossover design. An initial dose of 200-μg clonidine was replaced by 100 μg because of marked side effects. Twenty-one healthy male participants performed the visual-spatial cueing task while an electroencephalogram (EEG) was recorded. The behavioral output is the validity effect (benefit of cueing in terms of reaction time to targets). ERP indices for bias were the cue-related early directing attention negativity and late directing attention positivity, and the target-elicited P1 and N1 modulations by validity ('validity-effect'). The ERP index for disengagement was the target-elicited 'late positive deflection' modulation by validity. Behavioral analyses were performed on 16 participants, electrophysiological analyses on a subset (n=9). RESULTS: Clonidine attenuated the N1 effect, albeit in a subsample. Neither cue-elicited ERPs nor the behavioral validity effect were affected. Clonidine-induced blood pressure reduction was correlated with the reduction of the late positive deflection effect under clonidine. CONCLUSION: Clonidine attenuated the result of bias in a subsample and may have a modulating effect on disengagement.

After hearing a tone, the human auditory system becomes more sensitive to similar tones than to other tones. Current auditory models explain this phenomenon by a simple bandpass attention filter. Here, we demonstrate that auditory attention involves multiple pass-bands around octave-related frequencies above and below the cued tone. Intriguingly, this "octave effect" not only occurs for physically presented tones, but even persists for the missing fundamental in complex tones, and for imagined tones. Our results suggest neural interactions combining octave-related frequencies, likely located in nonprimary cortical regions. We speculate that this connectivity scheme evolved from exposure to natural vibrations containing octave-related spectral peaks, e.g., as produced by vocal cords. ispartof: Proceedings of the National Academy of Sciences of the United States of America vol:110 issue:38 pages:15225-15230 ispartof: location:United States status: published

Understanding the neuropharmacology of inhibition is of importance to fuel optimal treatment for disorders such as Attention Deficit/Hyperactivity Disorder. The aim of the present study was to assess the effect of noradrenergic antagonism by clonidine on behavioral-performance and brain-activity indices of inhibition. A placebo-controlled, double-blind, randomized, crossover design was implemented. Male (N = 21) participants performed in a visual stop signal task while EEG was recorded under clonidine in one session and under placebo in another. We expected that 100 μg clonidine would have a negative effect on EEG indices of inhibition, the Stop N2 and Stop P3. Furthermore, we expected that clonidine would negatively affect the behavioral measure of inhibition, the stop signal reaction time (SSRT). Behavioral analyses were performed on data of 17 participants, EEG analyses on a subset (N = 13). Performance data suggested that clonidine negatively affected attention (response variability, omissions) without affecting inhibition as indexed by SSRT. Electrophysiological data show that clonidine reduced the Stop P3, but not the Stop N2, indicating a partial negative effect on inhibition. Results show that it is unlikely that the Stop P3 reduction was related to the effect of clonidine on lapses of attention and on peripheral cardiovascular functioning. In conclusion, the current dose of clonidine had a negative effect on attention and a partial effect on inhibitory control. This inhibitory effect was restricted to the dorsal region of the prefrontal cortex (presumably the superior frontal gyrus) as opposed to the ventral region of the prefrontal cortex (right inferior frontal gyrus).

Multiple Complex Developmental Disorder (MCDD) is a well-defined and validated behavioral subtype of autism with a proposed elevated risk of developing a schizophrenic spectrum disorder. The current study investigated whether children with MCDD show the same deficits in sensory gating that are commonly reported in schizophrenia, or whether they are indistinguishable from children with autism in this respect. P50 suppression and prepulse inhibition (PPI) of the startle reflex were assessed in children with MCDD (n=14) or autism (n=13), and healthy controls (n=12), matched on age and IQ. All subjects showed high levels of PPI and P50 suppression. However, no group differences were found. No abnormalities in sensory filtering could be detected in children with autism or MCDD. Since sensory gating deficits are commonly regarded as possible endophenotypic markers for schizophrenia, the current results do not support a high level of similarity between schizophrenia and MCDD.

Autism is a neurodevelopmental disorder that usually arises on the basis of a complex genetic predisposition. The most significant susceptibility region in the first whole genome screen of multiplex families was on chromosome 7q, although this linkage was evident only in UK IMGSAC families. Subsequently all other genome screens of non-UK families have found some evidence of increased allele sharing in an overlapping 40 cM region of 7q. To further characterize this susceptibility locus, linkage analysis has now been completed on 170 multiplex IMGSAC families. Using a 5 cM marker grid, analysis of 125 sib pairs meeting stringent inclusion criteria resulted in a multipoint maximum LOD score (MLS) of 2.15 at D7S477, whereas analysis of all 153 sib pairs generated an MLS of 3.37. The 71 non-UK sib pairs now contribute to this linkage. Linkage disequilibrium mapping identified two regions of association-one lying under the peak of linkage, the other some 27 cM distal. These results are supported in part by findings in independent German and American singleton families.

Objective:To find out whether the neurodevelopmental disorders autism and childhood-onset schizophrenia have a common developmental pathway and whether the abnormalities detected are ‘disorder-specific’, by reviewing magnetic resonance imaging (MRI) studies.Methods:As a result of a Medline search, we were able to access 28 studies on autism and 12 studies on childhood-onset schizophrenia, which focused on children and adolescents.Results:Larger lateral ventricles were found to be a common abnormality in both disorders. ‘Disorder-specific’ abnormalities in patients with autism were larger brains, a larger thalamic area, and a smaller right cingulate gyrus. Subjects with childhood-onset schizophrenia were found to have smaller brains, a smaller amygdalum and thalamus, and a larger nucleus caudatus. In subjects with childhood-onset schizophrenia, abnormalities appeared to progress over a limited period of time.Conclusions:Because the study designs varied so much, the results should be interpreted cautiously. Before abnormalities found in the disorders can be designated as equal or ‘disorder-specific’, it will be essential to perform large longitudinal and cross-sectional follow-up studies.

Contains fulltext : 98353.pdf (Publisher’s version ) (Open Access) Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient's phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders. 01 november 2011

Background: A detailed visual processing style has been noted in autism spectrum disorder (ASD); this contributes to problems in face processing and has been directly related to abnormal processing of spatial frequencies (SFs). Little is known about the early development of face processing in ASD and the relation with abnormal SF processing. We investigated whether young ASD children show abnormalities in low spatial frequency (LSF, global) and high spatial frequency (HSF, detailed) processing and explored whether these are crucially involved in the early development of face processing.Methods: Three-to 4-year-old children with ASD (n = 22) were compared with developmentally delayed children without ASD (n = 17). Spatial frequency processing was studied by recording visual evoked potentials from visual brain areas while children passively viewed gratings (HSF/LSF). In addition, children watched face stimuli with different expressions, filtered to include only HSF or LSF.Results: Enhanced activity in visual brain areas was found in response to HSF versus LSF information in children with ASD, in contrast to control subjects. Furthermore, facial-expression processing was also primarily driven by detail in ASD.Conclusions: Enhanced visual processing of detailed (HSF) information is present early in ASD and occurs for neutral (gratings), as well as for socially relevant stimuli (facial expressions). These data indicate that there is a general abnormality in visual SF processing in early ASD and are in agreement with suggestions that a fast LSF subcortical face processing route might be affected in ASD. This could suggest that abnormal visual processing is causative in the development of social problems in ASD.

There is converging evidence for the presence of a fast subcortical face-processing route that operates on global face characteristics in the mature brain. Until now, little has been known about the development of such a route, which is surprising given suggestions that this fast subcortical face-processing route might be affected in neurodevelopmental disorders such as autism. To address this, early visual event-related potentials to pictures of fearful and neutral faces containing detailed or global information in 3- to 4-year-old (n = 20), 5- to 6-year-old (n = 25), and 7- to 8-year-old (n = 25) children were compared. In children, emotional processing was driven by detailed information. Developmental effects are discussed in terms of maturation of the fast subcortical face-processing route as well as an increase in experience with facial expressions with age.

Obsessive-compulsive disorder (OCD) is associated with deficits in inhibition mechanisms. This is reflected in reports showing impaired sensorimotor and sensory gating in OCD patients, as measured with prepulse inhibition (PPI) of the startle reflex and P50 suppression paradigms. However, most of the patients in these studies used medication and the results were not controlled for menstrual cycle phase in women. In this study PPI and P50 suppression were tested in 25 medication-free OCD patients and 25 healthy controls, using auditory stimuli and controlling for menstrual cycle effects. Subgroups were established, based on clinical variables (e.g. 'washers' and 'checkers'). No impairments in PPI or P50 suppression were found in the OCD group when compared with healthy controls. However, a subgroup of OCD patients ('checkers', n=12) showed increased P50 suppression. It was concluded that sensorimotor and sensory gating is not impaired in drug-free OCD patients, taking into account the menstrual cycle effects in women. These results do not support hypotheses linking deficits in these inhibition paradigms and the pathogenesis of OCD. The finding of an increased P50 suppression in the subgroup of 'checkers' deserves further investigation and underlines the value of studying subgroups of OCD.

Many genetic studies in autism have been performed, resulting in the identification of multiple linkage regions and cytogenetic aberrations, but little unequivocal evidence for the involvement of specific genes exists. By identifying novel symptoms in these patients, enhanced phenotyping of autistic individuals not only improves understanding and diagnosis but also helps to define biologically more homogeneous groups of patients, improving the potential to detect causative genes. Supported by recent copy number variation findings in autism, we hypothesized that for some susceptibility loci, autism resembles a contiguous gene syndrome, caused by aberrations within multiple (contiguous) genes, which jointly increases autism susceptibility. This would result in various different clinical manifestations that might be rather atypical, but that also co-occur with autism. To test this hypothesis, 13 susceptibility loci, identified through genetic linkage and cytogenetic analyses, were systematically analyzed. The Online Mendelian Inheritance in Man database was used to identify syndromes caused by mutations in the genes residing in each of these loci. Subsequent analysis of the symptoms expressed within these disorders allowed us to identify 33 symptoms (significantly more than expected, P = 0.037) that were over-represented in previous reports mapping to these loci. Some of these symptoms, including seizures and craniofacial abnormalities, support our hypothesis as they are already known to co-occur with autism. These symptoms, together with ones that have not previously been described to co-occur with autism, might be considered for use as inclusion or exclusion criteria toward defining etiologically more homogeneous groups for molecular genetic studies of autism European Journal of Human Genetics (2010) 18, 588-595; doi:10.1038/ejhg.2009.206; published online 25 November 2009

Onderzoek heeft laten zien dat mensen met autisme een basale afwijking in de visuele waarneming hebben. Deze waarnemingsafwijkingen zijn waarschijnlijk direct negatief gerelateerd aan het vermogen om op een optimale manier sociale informatie (zoals gezichten) te kunnen verwerken. De oorzaak van de waarnemingsafwijking heeft waarschijnlijk te maken met relatief kleine veranderingen in de communicatie tussen hersencellen in autisme. Om meer te begrijpen over de relatie tussen dergelijke subtiele veranderingen in hersenfunctioneren en de klinische symptomen van autisme, is ontwikkelingsonderzoek essentieel.

Autism spectrum disorders (ASD) and schizophrenia are both neurodevelopmental disorders that have extensively been associated with impairments in functional brain connectivity. Using a cross-sensory P50 suppression paradigm, this study investigated low-level audiovisual interactions on cortical EEG activation, which provides crucial information about functional integrity of connections between brain areas involved in cross-sensory processing in both disorders. Thirteen high functioning adult males with ASD, 13 high functioning adult males with schizophrenia, and 16 healthy adult males participated in the study. No differences in neither auditory nor cross-sensory P50 suppression were found between healthy controls and individuals with ASD. In schizophrenia, attenuated P50 responses to the first auditory stimulus indicated early auditory processing deficits. These results are in accordance with the notion that filtering deficits may be secondary to earlier sensory dysfunction. Also, atypical cross-sensory suppression was found, which implies that the cognitive impairments seen in schizophrenia may be due to deficits in the integrity of connections between brain areas involved in low-level cross-sensory processing. (C) 2009 Elsevier Ltd. All rights reserved.

The association between the 22q11.2 deletion syndrome (22q11DS) and psychiatric disorders, particularly psychosis, suggests a causal relationship between 22q11DS genes and abnormal brain function. The genes catechol-O-methyl-transferase (COMT) and proline dehydrogenase both reside within the commonly deleted region of 22q11.2. COMT activity and proline levels may therefore be altered in 22q11DS individuals. Associations of both COMT(158) genotype and elevated serum proline levels with abnormal brain function have been reported. Fifty-six 22q11DS children and 75 healthy controls were assessed on physiological measures of brain function, including prepulse inhibition (PPI) of startle, P50 auditory sensory gating and smooth pursuit eye movements (SPEM). COMT(158) genotype and plasma proline levels were determined in the 22q11DS children. We hypothesized an interaction between the COMT(158) genotype and proline, predicting the strongest negative effect of high proline on brain function to occur in 22q11DS children who are carriers of the COMT(met) allele. Of the three physiological measures, only SPEM and PPI were abnormal in the patient sample. With regard to the SPEM performance, there was a significant interaction between the COMT(158) genotype and proline level with significantly decreased SPEM performance in children with high plasma proline levels and the low activity COMT(met) allele. A similar interaction effect was not observed with regard to PPI. These findings are consistent with a model in which elevated proline negatively affects brain function by an increase in dopamine in the prefrontal cortex. 22q11DS patients with low dopamine catabolic capacity are therefore especially vulnerable to this functional disruption.

Background Schizophrenia is a highly heritable and complex disorder. Multiple genes are likely to be involved, complicating genetic research into the etiology of this disorder. Intermediate phenotypes or endophenotypes may facilitate genetic research if they display a simpler mode of transmission than schizophrenia itself, i.e., if they reflect more closely the underlying genetic effects. Methods Twenty-five multigenerational families with multiple members affected with schizophrenia (180 subjects) were administered an extensive neuropsychological, psychophysiological, and personality test battery. Familial correlations were calculated to select heritable traits. Subsequent heritability analysis followed by commingling and segregation analysis were performed to unravel the pattern of transmission and to estimate heritability. Results Five traits, including sensorimotor gating, openness, verbal fluency, early visual perception, and spatial working memory, showed moderate familial correlations. Heritability estimates for these traits ranged from 37% to 54%. A major gene model resembling dominant transmission was found for both sensorimotor gating and openness. Verbal fluency, early visual perception, and spatial working memory may be accounted for by polygenic, multifactorial, or environmental effects. Conclusions Only 2 of 13 candidate endophenotypes showed a simple mode of transmission useful for successful application in molecular genetic research: sensorimotor gating and openness. To our knowledge, this is the first study to investigate the pattern of transmission for these traits.

This study investigated self-monitoring in children with autism spectrum disorder (ASD) with event-related potentials looking at both the error-related negativity (ERN) and error-related positivity (Pe). The ERN is related to early error/conflict detection, and the Pe has been associated with conscious error evaluation or attention allocation. In addition, post-error slowing in reaction times (RTs) was measured. Children with ASD and age- and IQ- matched controls were administered an easy and a hard version of an auditory decision task. Results showed that the ERN was smaller in children with ASD but localized in the anterior cingulate cortex (ACC) in both groups. In addition we found a negativity on correct trials (CRN) that did not differ between the groups. Furthermore, a reduced Pe and a lack of post-error slowing in RTs were found in children with ASD. The reduced ERN in children with ASD, in the presence of an intact CRN, might suggest a specific insensitivity to detect situations in which the chance of making errors is enhanced. This might in turn lead to reduced error awareness/attention allocation to the erroneous event (reduced Pe) and eventually in a failure in change of strategy to deal with a situation, as becomes evident from the lack of post-error slowing in the ASD group. This relates well to the perseverative behaviour that is seen in children with ASD. We discuss these results in terms of a general deficit in self-monitoring, underlying social disturbance in ASD and the involvement of the ACC.

An important characteristic of autism spectrum disorder (ASD) is increased visual detail perception. Yet, there is no standing neurobiological explanation for this aspect of the disorder. We show evidence from EEG data, from 31 control subjects (three females) and 13 subjects (two females) aged 16-28 years, for a specific impairment in object boundary detection in ASD, which is present as early as 120 ms after stimulus presentation. In line with a neural network model explicating the role of feedforward, horizontal and recurrent processing in visual perception, we can attribute this deficit to a dysfunction of horizontal connections within early visual areas. Interestingly, ASD subjects showed an increase in subsequent activity at lateral occipital sites (225 ms), which might reflect a compensational mechanism. In contrast, recurrent processing between higher and lower visual areas (around 260 ms), associated with the segregation between figure and background, was normal. Our results show specific neural abnormalities in ASD related to low-level visual processing. In addition, given the reconciliation between our findings and previous neuropathology and neurochemistry research, we suggest that atypical horizontal interactions might reflect a more general neural abnormality in this disorder.

Background: Integration of information from multiple sensory sources is an important prerequisite for successful social behavior, especially during face-to-face conversation. It has been suggested that communicative impairments among individuals with pervasive developmental disorders (PDD) might be caused by an inability to integrate synchronously presented visual and auditory cues. Method: We investigated audiovisual integration of speech stimuli among a group of high-functioning adult PDD individuals and age- and IQ-matched controls using electroencephalography, measuring both early pre-phonological, as well as late phonologically driven integration. Results: Pre-phonological AV interactions are intact, while AV interactions corresponding to more complex phonological processes are impaired in individuals with PDD. Conclusions: The present findings argue for a pattern of impairments on tasks related to complex audiovisual integration combined with relative sparing of low-level integrational abilities. This combination may very well contribute to the communicative disabilities which are typical for the disorder.