Behavioral,cognitive, and adaptive development in infants with autism spectrum disorder in the first 2?years of life

Background

To delineate the early progression of autism spectrum disorder (ASD) symptoms, this study investigated developmental characteristics of infants at high familial risk for ASD (HR), and infants at low risk (LR).

Methods

Participants included 210 HR and 98 LR infants across 4 sites with comparable behavioral data at age 6, 12, and 24 months assessed in the domains of cognitive development (Mullen Scales of Early Learning), adaptive skills (Vineland Adaptive Behavioral Scales), and early behavioral features of ASD (Autism Observation Scale for Infants). Participants evaluated according to the DSM-IV-TR criteria at 24 months and categorized as ASD-positive or ASD-negative were further stratified by empirically derived cutoff scores using the Autism Diagnostic Observation Schedule yielding four groups: HR-ASD-High, HR-ASD-Moderate (HR-ASD-Mod), HR-ASD-Negative (HR-Neg), and LR-ASD-Negative (LR-Neg).

Results

The four groups demonstrated different developmental trajectories that became increasingly distinct from 6 to 24 months across all domains. At 6 months, the HR-ASD-High group demonstrated less advanced Gross Motor and Visual Reception skills compared with the LR-Neg group. By 12 months, the HR-ASD-High group demonstrated increased behavioral features of ASD and decreased cognitive and adaptive functioning compared to the HR-Neg and LR-Neg groups. By 24 months, both the HR-ASD-High and HR-ASD-Moderate groups demonstrated differences from the LR- and HR-Neg groups in all domains.

Conclusions

These findings reveal atypical sensorimotor development at 6 months of age which is associated with ASD at 24 months in the most severely affected group of infants. Sensorimotor differences precede the unfolding of cognitive and adaptive deficits and behavioral features of autism across the 6- to 24-month interval. The less severely affected group demonstrates later symptom onset, in the second year of life, with initial differences in the social-communication domain.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9117-6) contains supplementary material, which is available to authorized users.     

Event-related potentials to repeated speech in 9-month-old infants at risk for autism spectrum disorder

Background

Atypical neural responses to repeated auditory and linguistic stimuli have been reported both in individuals with autism spectrum disorder (ASD) and their first-degree relatives. Recent work suggests that the younger siblings of children with ASD have atypical event-related potentials (ERPs) to repeated tones at 9 months of age; however, the functional significance is unclear, and it is unknown whether this atypicality is also present in response to linguistic stimuli.

Methods

We analyzed ERPs to repetitive and deviant consonant-vowel stimuli at 9 months in 35 unaffected high-risk-for-autism (HRA) infant siblings of children with ASD and 45 low-risk control (LRC) infants. We examined a positive component, the P150, over frontal and central electrode sites and investigated the relationships between this component and later behavior.

Results

Over frontal electrodes, HRA infants had larger-amplitude ERPs to repetitions of the standard than LRC infants, whereas ERPs to the deviant did not differ between HRA and LRC infants. Furthermore, for HRA infants, the amplitude of ERPs to the standards was positively correlated with later language ability.

Conclusions

Our work suggests that atypical ERPs to repeated speech during infancy are a possible endophenotype of ASD but that this atypicality is associated with beneficial, rather than disordered, language development. Potential mechanisms driving these relationships and implications for development are discussed.     

Altered modulation of gamma oscillation frequency by speed of visual motion in children with autism spectrum disorders

Background

Recent studies link autism spectrum disorders (ASD) with an altered balance between excitation and inhibition (E/I balance) in cortical networks. The brain oscillations in high gamma-band (50–120 Hz) are sensitive to the E/I balance and may appear useful biomarkers of certain ASD subtypes. The frequency of gamma oscillations is mediated by level of excitation of the fast-spiking inhibitory basket cells recruited by increasing strength of excitatory input. Therefore, the experimental manipulations affecting gamma frequency may throw light on inhibitory networks dysfunction in ASD.

Methods

Here, we used magnetoencephalography (MEG) to investigate modulation of visual gamma oscillation frequency by speed of drifting annular gratings (1.2, 3.6, 6.0 °/s) in 21 boys with ASD and 26 typically developing boys aged 7–15 years. Multitaper method was used for analysis of spectra of gamma power change upon stimulus presentation and permutation test was applied for statistical comparisons. We also assessed in our participants visual orientation discrimination thresholds, which are thought to depend on excitability of inhibitory networks in the visual cortex.

Results

Although frequency of the oscillatory gamma response increased with increasing velocity of visual motion in both groups of participants, the velocity effect was reduced in a substantial proportion of children with ASD. The range of velocity-related gamma frequency modulation correlated inversely with the ability to discriminate oblique line orientation in the ASD group, while no such correlation has been observed in the group of typically developing participants.

Conclusions

Our findings suggest that abnormal velocity-related gamma frequency modulation in ASD may constitute a potential biomarker for reduced excitability of fast-spiking inhibitory neurons in a subset of children with ASD.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9121-x) contains supplementary material, which is available to authorized users.     

Enhanced parietal cortex activation during location detection in children with autism

Background

Visuospatial processing has been found to be mediated primarily by two cortical routes, one of which is unique to recognizing objects (occipital-temporal, ventral or “what” pathway) and the other to detecting the location of objects in space (parietal-occipital, dorsal or “where” pathway). Considering previous findings of relative advantage in people with autism in visuospatial processing, this functional MRI study examined the connectivity in the dorsal and ventral pathways in high-functioning children with autism.

Methods

Seventeen high-functioning children and adolescents with autism spectrum disorders (ASD) and 19 age-and-IQ-matched typically developing (TD) participants took part in this study. A simple visual task involving object recognition and location detection was used. In the MRI scanner, participants were shown grey scale pictures of objects (e.g., toys, household items, etc.) and were asked to identify the objects presented or to specify the location of objects relative to a cross at the center of the screen.

Results

Children with ASD, relative to TD children, displayed significantly greater activation in the left inferior parietal lobule (especially the angular gyrus) while detecting the location of objects. However, there were no group differences in brain activity during object recognition. There were also differences in functional connectivity, with the ASD participants showing decreased connectivity of the inferior temporal area with parietal and occipital areas during location detection.

Conclusions

The results of this study underscore previous findings of an increased reliance on visuospatial processing (increased parietal activation) for information processing in ASD individuals. In addition, such processing may be more local, focal, and detailed in ASD as evidenced from the weaker functional connectivity.

Electronic supplementary material

The online version of this article (doi:10.1186/1866-1955-6-37) contains supplementary material, which is available to authorized users.     

Organization of brain networks governed by long-range connections index autistic traits in the general population

Background

The dimensional approach to autism spectrum disorder (ASD) considers ASD as the extreme of a dimension traversing through the entire population. We explored the potential utility of electroencephalography (EEG) functional connectivity as a biomarker. We hypothesized that individual differences in autistic traits of typical subjects would involve a long-range connectivity diminution within the delta band.

Methods

Resting-state EEG functional connectivity was measured for 74 neurotypical subjects. All participants also provided a questionnaire (Social Responsiveness Scale, SRS) that was completed by an informant who knows the participant in social settings. We conducted multivariate regression between the SRS score and functional connectivity in all EEG frequency bands. We explored modulations of network graph metrics characterizing the optimality of a network using the SRS score.

Results

Our results show a decay in functional connectivity mainly within the delta and theta bands (the lower part of the EEG spectrum) associated with an increasing number of autistic traits. When inspecting the impact of autistic traits on the global organization of the functional network, we found that the optimal properties of the network are inversely related to the number of autistic traits, suggesting that the autistic dimension, throughout the entire population, modulates the efficiency of functional brain networks.

Conclusions

EEG functional connectivity at low frequencies and its associated network properties may be associated with some autistic traits in the general population.     

Neural synchrony examined with magnetoencephalography (MEG) during eye gaze processing in autism spectrum disorders: preliminary findings

Background

Gaze processing deficits are a seminal, early, and enduring behavioral deficit in autism spectrum disorder (ASD); however, a comprehensive characterization of the neural processes mediating abnormal gaze processing in ASD has yet to be conducted.

Methods

This study investigated whole-brain patterns of neural synchrony during passive viewing of direct and averted eye gaze in ASD adolescents and young adults (M _Age  = 16.6) compared to neurotypicals (NT) (M _Age  = 17.5) while undergoing magnetoencephalography. Coherence between each pair of 54 brain regions within each of three frequency bands (low frequency (0 to 15 Hz), beta (15 to 30 Hz), and low gamma (30 to 45 Hz)) was calculated.

Results

Significantly higher coherence and synchronization in posterior brain regions (temporo-parietal-occipital) across all frequencies was evident in ASD, particularly within the low 0 to 15 Hz frequency range. Higher coherence in fronto-temporo-parietal regions was noted in NT. A significantly higher number of low frequency cross-hemispheric synchronous connections and a near absence of right intra-hemispheric coherence in the beta frequency band were noted in ASD. Significantly higher low frequency coherent activity in bilateral temporo-parieto-occipital cortical regions and higher gamma band coherence in right temporo-parieto-occipital brain regions during averted gaze was related to more severe symptomology as reported on the Autism Diagnostic Interview-Revised (ADI-R).

Conclusions

The preliminary results suggest a pattern of aberrant connectivity that includes higher low frequency synchronization in posterior cortical regions, lack of long-range right hemispheric beta and gamma coherence, and decreased coherence in fronto-temporo-parietal regions necessary for orienting to shifts in eye gaze in ASD; a critical behavior essential for social communication.     

Modulation of mu attenuation to social stimuli in children and adults with 16p11.2 deletions and duplications

Background

Copy number variations (CNV) within the recurrent ~600 kb chromosomal locus of 16p11.2 are associated with a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, little is known about the social brain phenotype of 16p11.2 CNV and how this phenotype is related to the social impairments associated with CNVs at this locus. The aim of this preliminary study was to use molecular subtyping to establish the social brain phenotype of individuals with 16p11.2 CNV and how these patterns relate to typical development and ASD.

Methods

We evaluated the social brain phenotype as expressed by mu attenuation in 48 children and adults characterized as duplication carriers (n = 12), deletion carriers (n = 12), individuals with idiopathic ASD (n = 8), and neurotypical controls (n = 16). Participants watched videos containing social and nonsocial motion during electroencephalogram (EEG) acquisition.

Results

Overall, only the typical group exhibited predicted patterns of mu modulation to social information (e.g., greater mu attenuation for social than nonsocial motion). Both 16p11.2 CNV groups exhibited more mu attenuation for nonsocial than social motion. The ASD group did not discriminate between conditions and demonstrated less mu attenuation compared to the typical and duplication carriers. Single-trial analysis indicated that mu attenuation decreased over time more rapidly for 16p11.2 CNV groups than the typical group. The duplication group did not diverge from typical patterns of mu attenuation until after initial exposure.

Conclusions

These results indicate atypical but unique patterns of mu attenuation for deletion and duplication carriers, highlighting the need to continue characterizing the social brain phenotype associated with 16p11.2 CNVs.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9118-5) contains supplementary material, which is available to authorized users.     

High rates of parkinsonism in adults with autism

Background

While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition.

Methods

We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson’s disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism.

Results

Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism.

Conclusions

We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson’s disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism.     

Structural and functional connectivity in the default mode network in 22q11.2 deletion syndrome

Background

The neural endophenotype associated with 22q11.2 deletion syndrome (22q11DS) includes deviant cortical development and alterations in brain connectivity. Resting-state functional magnetic resonance imaging (fMRI) findings also reported disconnectivity within the default mode network (DMN). In this study, we explored the relationship between functional and structural DMN connectivity and their changes with age in patients with 22q11DS in comparison to control participants. Given previous evidence of an association between DMN disconnectivity and the manifestation of psychotic symptoms, we further investigated this relationship in our group of patients with 22q11DS.

Methods

T1-weighted, diffusion, and resting-state fMRI scans were acquired from 41 patients with 22q11DS and 43 control participants aged 6 to 28 years. A data-driven approach based on independent component analysis (ICA) was used to identify the DMN and to define regions of interest for the structural and functional connectivity analysis. Prodromal psychotic symptoms were assessed in adolescents and adults using the positive symptom scores of the Structured Interview of Prodromal Syndromes (SIPS). Connectivity measures were compared between groups and correlated with age. Repeating the between-group analysis in three different age bins further assessed the presence of age-related alterations in DMN connectivity. Structural and functional connectivity measures were then correlated with the SIPS scores.

Results

A simultaneous reduction of functional and structural connectivity between core medial nodes of the DMN was observed. Furthermore, structural connectivity measures significantly increased with age in the control group but not in patients with 22q11DS, suggesting the presence of an age-related alteration of the DMN structural connections. No correlations were found between the DMN disconnectivity and expression of prodromal symptoms in 22q11DS.

Conclusions

These findings indicate the presence of functional and structural DMN disconnectivity in 22q11DS and that patients with 22q11DS fail to develop normal structural connections between medial DMN nodes. This suggests the presence of altered neurodevelopmental trajectories in 22q11DS.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9120-y) contains supplementary material, which is available to authorized users.     

The perinatal androgen to estrogen ratio and autistic-like traits in the general population: a longitudinal pregnancy cohort study

Background

Prenatal androgen exposure has been hypothesized to be linked to autism spectrum disorder (ASD). While previous studies have found a link between testosterone levels in amniotic fluid and autistic-like traits, a similar relationship has not been found for testosterone in umbilical cord blood. However, it may be the net biological activity of multiple androgens and estrogens that influences postnatal effects of prenatal sex steroids. Accordingly, composite levels of androgens (A) and estrogens (E) were investigated, along with their ratio, in relation to autistic-like traits in young adulthood.

Methods

Sex steroid data in umbilical cord blood were available from 860 individuals at delivery. Samples were analyzed for androgens (testosterone, androstenedione, and dehydroepiandrosterone) and estrogens (estrone, estradiol, estriol, and estetrol). Levels of bioavailable testosterone, estradiol, and estrone were measured and used to calculate A and E composites and the A to E ratio. Participants were approached in early adulthood to complete the autism-spectrum quotient (AQ) as a self-report measure of autistic-like traits, with 183 males (M = 20.10 years, SD = 0.65 years) and 189 females (M =19.92 years, SD = 0.68 years) providing data.

Results

Males exhibited significantly higher androgen composites and A to E composite ratios than females. Males also scored significantly higher on the details/patterns subscale of the AQ. Subsequent categorical and continuous analyses, which accounted for covariates, revealed no substantial relationships between the A/E composites or the A to E ratio and the AQ total or subscale scores.

Conclusions

The current study found no link between the A/E composites or the A to E ratio in cord blood and autistic-like traits in the population as measured by the AQ. These outcomes do not exclude the possibility that these sex steroid variables may predict other neurodevelopmental traits in early development.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9114-9) contains supplementary material, which is available to authorized users.     

Decoding the processing of lying using functional connectivity MRI

Background

Previous functional MRI (fMRI) studies have demonstrated group differences in brain activity between deceptive and honest responses. The functional connectivity network related to lie-telling remains largely uncharacterized.

Methods

In this study, we designed a lie-telling experiment that emphasized strategy devising. Thirty-two subjects underwent fMRI while responding to questions in a truthful, inverse, or deceitful manner. For each subject, whole-brain functional connectivity networks were constructed from correlations among brain regions for the lie-telling and truth-telling conditions. Then, a multivariate pattern analysis approach was used to distinguish lie-telling from truth-telling based on the functional connectivity networks.

Results

The classification results demonstrated that lie-telling could be differentiated from truth-telling with an accuracy of 82.81% (85.94% for lie-telling, 79.69% for truth-telling). The connectivities related to the fronto-parietal networks, cerebellum and cingulo-opercular networks are most discriminating, implying crucial roles for these three networks in the processing of deception.

Conclusions

The current study may shed new light on the neural pattern of deception from a functional integration viewpoint.

Electronic supplementary material

The online version of this article (doi:10.1186/s12993-014-0046-4) contains supplementary material, which is available to authorized users.     

Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder

Background

Convergent evidence suggests dysfunction within the prefrontal cortex (PFC) and amygdala, important components of a neural system that subserves emotional processing, in individuals with major depressive disorder (MDD). Abnormalities in this system in the left hemisphere and during processing of negative emotional stimuli are especially implicated. In this study, we used functional magnetic resonance imaging (fMRI) to investigate amygdala–PFC functional connectivity during emotional face processing in medication-naive individuals with MDD.

Methods

Individuals with MDD and healthy controls underwent fMRI scanning while processing 3 types of emotional face stimuli. We compared the strength of functional connectivity from the amygdala between the MDD and control groups.

Results

Our study included 28 individuals with MDD and 30 controls. Decreased amygdala–left rostral PFC (rPFC) functional connectivity was observed in the MDD group compared with controls for the fear condition (p < 0.05, corrected). No significant differences were found in amygdala connectivity to any cerebral regions between the MDD and control groups for the happy or neutral conditions.

Limitations

All participants with MDD were experiencing acute episodes, therefore the findings could not be generalized to the entire MDD population.

Conclusion

Medication-naive individuals with MDD showed decreased amygdala–left rPFC functional connectivity in response to negative emotional stimuli, suggesting that abnormalities in amygdala–left rPFC neural circuitry responses to negative emotional stimuli might play an important role in the pathophysiology of MDD.     

Neural circuitry of emotional face processing in autism spectrum disorders

Background

Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces.

Methods

Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces.

Results

In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces.

Limitations

The small sample size may have affected our ability to detect additional group differences.

Conclusion

When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.     

A multidisciplinary approach unravels early and persistent effects of X-ray exposure at the onset of prenatal neurogenesis

Background

In humans, in utero exposure to ionising radiation results in an increased prevalence of neurological aberrations, such as small head size, mental retardation and decreased IQ levels. Yet, the association between early damaging events and long-term neuronal anomalies remains largely elusive.

Methods

Mice were exposed to different X-ray doses, ranging between 0.0 and 1.0 Gy, at embryonic days (E) 10, 11 or 12 and subjected to behavioural tests at 12 weeks of age. Underlying mechanisms of irradiation at E11 were further unravelled using magnetic resonance imaging (MRI) and spectroscopy, diffusion tensor imaging, gene expression profiling, histology and immunohistochemistry.

Results

Irradiation at the onset of neurogenesis elicited behavioural changes in young adult mice, dependent on the timing of exposure. As locomotor behaviour and hippocampal-dependent spatial learning and memory were most particularly affected after irradiation at E11 with 1.0 Gy, this condition was used for further mechanistic analyses, focusing on the cerebral cortex and hippocampus. A classical p53-mediated apoptotic response was found shortly after exposure. Strikingly, in the neocortex, the majority of apoptotic and microglial cells were residing in the outer layer at 24 h after irradiation, suggesting cell death occurrence in differentiating neurons rather than proliferating cells. Furthermore, total brain volume, cortical thickness and ventricle size were decreased in the irradiated embryos. At 40 weeks of age, MRI showed that the ventricles were enlarged whereas N-acetyl aspartate concentrations and functional anisotropy were reduced in the cortex of the irradiated animals, indicating a decrease in neuronal cell number and persistent neuroinflammation. Finally, in the hippocampus, we revealed a reduction in general neurogenic proliferation and in the amount of Sox2-positive precursors after radiation exposure, although only at a juvenile age.

Conclusions

Our findings provide evidence for a radiation-induced disruption of mouse brain development, resulting in behavioural differences. We propose that alterations in cortical morphology and juvenile hippocampal neurogenesis might both contribute to the observed aberrant behaviour. Furthermore, our results challenge the generally assumed view of a higher radiosensitivity in dividing cells. Overall, this study offers new insights into irradiation-dependent effects in the embryonic brain, of relevance for the neurodevelopmental and radiobiological field.

Electronic supplementary material

The online version of this article (doi:10.1186/1866-1955-7-3) contains supplementary material, which is available to authorized users.     

Band-specific atypical functional connectivity pattern in childhood autism spectrum disorder

Objective

Altered brain connectivity has been theorized as a key neural underpinning of autism spectrum disorder (ASD), but recent investigations have revealed conflicting patterns of connectivity, particularly hyper-connectivity and hypo-connectivity across age groups. The application of graph theory to neuroimaging data has become an effective approach for characterizing topographical patterns of large-scale functional networks. We used a graph approach to investigate alteration of functional networks in childhood ASD.

Resting-state functional connectivity abnormalities in patients with obsessive–compulsive disorder and their healthy first-degree relatives

Background

Obsessive–compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysfunction of brain cortical–striatal–thalamic–cortical (CSTC) circuits; however, the extent of brain functional abnormalities in individuals with OCD is unclear, and the genetic basis of this disorder is poorly understood. We determined the whole brain functional connectivity patterns in patients with OCD and their healthy first-degree relatives.

Methods

We used resting-state fMRI to measure functional connectivity strength in patients with OCD, their healthy first-degree relatives and healthy controls. Whole brain functional networks were constructed by measuring the temporal correlations of all brain voxel pairs and further analyzed using a graph theory approach.

Results

We enrolled 39 patients with OCD, 20 healthy first-degree relatives and 39 healthy controls in our study. Compared with healthy controls, patients with OCD showed increased functional connectivity primarily within the CSTC circuits and decreased functional connectivity in the occipital cortex, temporal cortex and cerebellum. Moreover, patients with OCD and their first-degree relatives exhibited overlapping increased functional connectivity strength in the bilateral caudate nucleus, left orbitofrontal cortex (OFC) and left middle temporal gyrus.

Limitations

Potential confounding factors, such as medication use, heterogeneity in symptom clusters and comorbid disorders, may have impacted our findings.

Conclusion

Our preliminary results suggest that patients with OCD have abnormal resting-state functional connectivity that is not limited to CSTC circuits and involves abnormalities in additional large-scale brain systems, especially the limbic system. Moreover, resting-state functional connectivity strength abnormalities in the left OFC, bilateral caudate nucleus and left middle temporal gyrus may be neuroimaging endophenotypes for OCD.     

Robust features for the automatic identification of autism spectrum disorder in children

Background

It is commonly reported that children with autism spectrum disorder (ASD) exhibit hyper-reactivity or hypo-reactivity to sensory stimuli. Electroencephalography (EEG) is commonly used to study neural sensory reactivity, suggesting that statistical analysis of EEG recordings is a potential means of automatic classification of the disorder. EEG recordings taken from children, however, are frequently contaminated with large amounts of noise, making analysis difficult. In this paper, we present a method for the automatic extraction of noise-robust EEG features, which serve to quantify neural sensory reactivity. We show the efficacy of a system for the classification of ASD using these features.

Methods

An oddball paradigm was used to elicit event-related potentials from a group of 19 ASD children and 30 typically developing children. EEG recordings were taken and robust features were extracted. A support vector machine, logistic regression, and a naive Bayes classifier were used to classify the children as having ASD or being typically developing.

Results

A classification accuracy of 79% was achieved, making our method competitive with other automatic diagnosis methods based on EEG. Additionally, we found that classification performance is reduced if eye blink artifacts are removed during preprocessing.

Conclusions

This study shows that robust EEG features that quantify neural sensory reactivity are useful for the classification of ASD. We showed that noise-robust features are crucial for our analysis, and observe that traditional preprocessing methods may lead to poor classification performance in the face of a large amount of noise. Further exploration of alternative preprocessing methods is warranted.     

Static and Dynamic Characteristics of Cerebral Blood Flow During the Resting State in Schizophrenia

Background:

The cerebral network that is active during rest and is deactivated during goal-oriented activity is called the default mode network (DMN). It appears to be involved in self-referential mental activity. Atypical functional connectivity in the DMN has been observed in schizophrenia. One hypothesis suggests that pathologically increased DMN connectivity in schizophrenia is linked with a main symptom of psychosis, namely, misattribution of thoughts.

Methods:

A resting-state pseudocontinuous arterial spin labeling (ASL) study was conducted to measure absolute cerebral blood flow (CBF) in 34 schizophrenia patients and 27 healthy controls. Using independent component analysis (ICA), the DMN was extracted from ASL data. Mean CBF and DMN connectivity were compared between groups using a 2-sample t test.

Results:

Schizophrenia patients showed decreased mean CBF in the frontal and temporal regions (P < .001). ICA demonstrated significantly increased DMN connectivity in the precuneus (x/y/z = −16/−64/38) in patients than in controls (P < .001). CBF was not elevated in the respective regions. DMN connectivity in the precuneus was significantly correlated with the Positive and Negative Syndrome Scale scores (P < .01).

Conclusions:

In schizophrenia patients, the posterior hub—which is considered the strongest part of the DMN—showed increased DMN connectivity. We hypothesize that this increase hinders the deactivation of the DMN and, thus, the translation of cognitive processes from an internal to an external focus. This might explain symptoms related to defective self-monitoring, such as auditory verbal hallucinations or ego disturbances.Key words: psychosis, default mode network, arterial spin labeling, functional connectivity, precuneus     

Sleep EEG Characteristics in Young and Elderly Patients with Obstructive Sleep Apnea Syndrome

Objective

In the present study, it was hypothesized that the sleep electroencephalogram (EEG) characteristics of young (<30 yrs) and elderly (>55 yrs) OSAS patients would differ.

Methods

We analyzed 76 sleep EEG recordings from OSAS patients (young group: n=40, mean age: 24.3±4.9 yrs; elderly group: n=36, mean age: 59.1±4.9 yrs), which were obtained during nocturnal polysomnography. The recordings were assessed via spectral analysis in the delta (0.5–4.5 Hz), theta (4.5–8 Hz), alpha (8–12 Hz), beta (12–32 Hz), slow sigma (11–13 Hz), and fast sigma (13–17 Hz) frequency bands.

Results

Apnea Hypopnea Index (AHI) and sleep efficiency (%) did not differ significantly between the two groups (19.8±14.4 vs. 25.9±16.0, p=0.085; 84.4±12.6 vs. 80.9±11.0, p=0.198, respectively). After adjusting for gender, the slow/fast sigma ratio was not significantly correlated with AHI in the elderly group (r=-0.047, p=0.790) but AHI was inversely correlated with the slow/fast sigma ratio in the young group (r=-0.423, p=0.007). A multiple linear regression analysis revealed that a higher AHI was related with a lower slow/fast sigma ratio in the young group (β=-0.392, p=0.028) but not the elderly.

Conclusion

In the present study, sleep EEG activity differed between young and elderly OSAS patients. The slow/fast sigma ratio was associated with OSAS severity only in young patients, suggesting that young OSAS patients may have a distinctive brain plasticity compared with elderly patients.