Connectivity-Based Parcellation of the Amygdala Predicts Social Skills in Adolescents with Autism Spectrum Disorder.

Amygdala dysfunction plays a role in the social impairments in autism spectrum disorders (ASD), but it is unclear which of its subregions are abnormal in ASD. This study compared the volume and functional connectivity (FC) strength of three FC-defined amygdala subregions between ASD and controls, and assessed their relation to social skills in ASD. A subregion associated with the social perception network was enlarged in ASD (F1 = 7.842, p = .008) and its volume correlated significantly with symptom severity (social skills: r = .548, p = .009). Posthoc analysis revealed that the enlargement was driven by the vmPFC amygdala network. These findings refine our understanding of abnormal amygdala connectivity in ASD and may inform future strategies for therapeutic interventions targeting the amygdalofrontal pathway.

Decreased Left Caudate Volume Is Associated with Increased Severity of Autistic-Like Symptoms in a Cohort of ADHD Patients and Their Unaffected Siblings.

Autism spectrum disorder (ASD) symptoms frequently occur in individuals with attention-deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural brain correlates, knowledge of the structural brain profile of individuals with ADHD with raised ASD symptoms is limited. The presence of ASD-like symptoms was measured by the Children's Social Behavior Questionnaire (CSBQ) in a sample of typically developing controls (n = 154), participants with ADHD (n = 239), and their unaffected siblings (n = 144) between the ages of 8 and 29. Structural magnetic resonance imaging (MRI) correlates of ASD ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for ADHD symptom count and total brain volume. ASD ratings were significantly elevated in participants with ADHD relative to controls and unaffected siblings. For the entire group (participants with ADHD, unaffected siblings and TD controls), mixed effect models revealed that the left caudate nucleus volume was negatively correlated with ASD ratings (t = 2.83; P = 0.005). The current findings are consistent with the role of the caudate nucleus in executive function, including the selection of goals based on the evaluation of action outcomes and the use of social reward to update reward representations. There is a specific volumetric profile associated with subclinical ASD-like symptoms in participants with ADHD, unaffected siblings and controls with the caudate nucleus and globus pallidus being of critical importance in predicting the level of ASD-like symptoms in all three groups.

Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study.

BACKGROUND: Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls. METHODS: We collected resting state functional magnetic resonance imaging (fMRI) data, tailored to provide optimal sensitivity in the amygdala as well as the neocortex, in 20 adolescents and young adults with ASD and 25 matched controls. We performed a regular correlation analysis between the entire amygdala (EA) and the whole brain and used a partial correlation analysis to investigate whole-brain functional connectivity uniquely related to each of the amygdaloid subregions. RESULTS: Between-group comparison of regular EA correlations showed significantly reduced connectivity in visuospatial and superior parietal areas in ASD compared to controls. Partial correlation analysis revealed that this effect was driven by the left superficial and right laterobasal input subregions, but not the centromedial output nuclei. CONCLUSIONS: These results indicate reduced connectivity of specifically the amygdaloid sensory input channels in ASD, suggesting that abnormal amygdalo-cortical connectivity can be traced down to the socio-perceptual pathways.

Gender and age differences in the core triad of impairments in autism spectrum disorders: a systematic review and meta-analysis.

Autism is an extensively studied disorder in which the gender disparity in prevalence has received much attention. In contrast, only a few studies examine gender differences in symptomatology. This systematic review and meta-analysis of 22 peer reviewed original publications examines gender differences in the core triad of impairments in autism. Gender differences were transformed and concatenated using standardized mean differences, and analyses were stratified in five age categories (toddlerhood, preschool children, childhood, adolescence, young adulthood). Boys showed more repetitive and stereotyped behavior as from the age of six, but not below the age of six. Males and females did not differ in the domain of social behavior and communication. There is an underrepresentation of females with ASD an average to high intelligence. Females could present another autistic phenotype than males. As ASD is now defined according to the male phenotype this could imply that there is an ascertainment bias. More research is needed into the female phenotype of ASD with development of appropriate instruments to detect and ascertain them.

Paralimbic cortical thickness in first-episode depression: evidence for trait-related differences in mood regulation.

OBJECTIVE: Impaired mood regulation is a key deficit of major depressive disorder that is primarily mediated by an interaction between the paralimbic cortex (i.e., orbitofrontal, cingulate, insular, parahippocampal, and temporopolar cortices) and limbic regions. The authors investigated whether depressed patients and healthy comparison subjects have differences in cortical thickness in the paralimbic cortex and whether potential differences are evident only during a depressive state or are trait related. METHOD: Forty patients with a first episode of major depressive disorder participated: 20 medication-naive currently depressed patients and 20 medication-free recovered patients. The patients and 31 matched healthy comparison subjects underwent structural magnetic resonance imaging. Group differences in mean cortical thickness of the paralimbic cortex were measured by using FreeSurfer software, with adjustment for age, sex, and intracranial volume, and subgroup analyses were performed to assess state and trait effects. RESULTS: The medial orbitofrontal cortex was thinner in the depressed patients than in the comparison subjects. Greater thickness was present in the temporal pole and the caudal anterior and posterior cingulate cortex. All changes were trait related. CONCLUSIONS: The data provide evidence that even early in the course of depression brain regions involved in mood regulation show trait-related differences in cortical thickness.

Visual scanning in very young children with autism and their unaffected parents.

This study of gaze patterns in very young children with autism and their parents included 23 cases (with 16 fathers and 19 mothers) and 46 controls (with 14 fathers and 28 mothers). Children (mean age 3.3 ± 1.5 years) with autism met DSM-IV and ADOS-G diagnostic criteria. The participants' gaze patterns were recorded while they viewed four simple movies that did not feature people. In children, severity of autism is related to spending more time watching irrelevant regions in one of the four movies. The mothers of children with autism showed an atypical pattern for three movies, whereas the fathers of children with autism did not show an atypical gaze pattern. The gaze pattern of the mothers was positively correlated with that of their children. The atypical viewing pattern of autistic individuals appears not to be restricted to people and social situations but is also seen in other situations, suggesting that there is a perceptual broad autism phenotype.

Pervasive microstructural abnormalities in autism: a DTI study.

BACKGROUND: Recent studies have reported abnormal functional connectivity patterns in the brains of people with autism that may be accompanied by decreases in white matter integrity. Since autism is a developmental disorder, we aim to investigate the nature and location of decreases in white and grey matter integrity in an adolescent sample while accounting for age. METHODS: We used structural (T1) imaging to study brain volumetrics and diffusion tensor imaging (DTI) to investigate white and grey matter integrity in people with autism. We obtained magnetic resonance images for adolescents aged 12-18 years with high-functioning autism and from matched controls. Fractional anisotropy and mean diffusivity, as well as grey and white matter volumetrics were analyzed. RESULTS: There were 17 participants with autism and 25 matched controls included in this study. Participants with autism had lower fractional anisotropy in the left and right superior and inferior longitudinal fasciculus, but this effect was not significant after adjusting for age and intelligence quotient (IQ). The kurtosis of the white matter fractional anisotropy probability distribution was higher in this participant group, with and without adjustment for age and IQ. Most notably, however, the mean diffusivity levels were markedly increased in the autism group throughout the brain, and the mean diffusivity probability distributions of both grey and white matter were shifted toward a higher value, particularly with age and IQ adjustment. No volumetric differences in grey and white matter were found. LIMITATIONS: We corrected for age and IQ using a linear model. The study was also limited by its sample size, investigated age range and cross-sectional design. CONCLUSION: The findings suggest that autism is characterized by a generalized reduction of white matter integrity that is associated with an increase of interstitial space. The generalized manifestation of the white matter abnormalities provides an important new perspective on autism as a connectivity disorder.

Altered intrinsic functional connectivity of anterior and posterior insula regions in high-functioning participants with autism spectrum disorder.

Impaired understanding of others' sensations and emotions as well as abnormal experience of their own emotions and sensations is frequently reported in individuals with Autism Spectrum Disorder (ASD). It is hypothesized that these abnormalities are based on altered connectivity within "shared" neural networks involved in emotional awareness of self and others. The insula is considered a central brain region in a network underlying these functions, being located at the transition of information about bodily arousal and the physiological state of the body to subjective feelings. The present study investigated the intrinsic functional connectivity properties of the insula in 14 high-functioning participants with ASD (HF-ASD) and 15 typically developing (TD) participants in the age range between 12 and 20 years by means of "resting state" or "nontask" functional magnetic resonance imaging. Essentially, a distinction was made between anterior and posterior regions of the insular cortex. The results show a reduced functional connectivity in the HF-ASD group, compared with the TD group, between anterior as well as posterior insula and specific brain regions involved in emotional and sensory processing. It is suggested that functional abnormalities in a network involved in emotional and interoceptive awareness might be at the basis of altered emotional experiences and impaired social abilities in ASD, and that these abnormalities are partly based on the intrinsic functional connectivity properties of such a network.

Diagnosing autism spectrum disorders in elderly people.

BACKGROUND: As autism spectrum disorders (ASD) have largely been neglected in old-age psychiatry, the objective of the present paper is to describe the diagnostic process in elderly patients. METHODS: A systematic review of the literature on ASD in older age was undertaken and illustrated by a case series of three elderly patients first diagnosed with ASD in later life by a tertiary mental health clinic. RESULTS: The search of the literature only yielded three papers on late-life ASD, while the review of the available diagnostic procedures among adults suggests some relevance for screening instruments (Autism Questionnaire), diagnostic instruments (Module 4, Autism Diagnostic Observation Schedule), and neuropsychological examination to profile impairments. Nonetheless, the case reports clearly showed that taking a thorough history with the patient, corroborated and supplemented by a close relative or caregiver who has known the patient for at least ten years, still remains the most important diagnostic tool. CONCLUSION: The three case studies show that in clinical practice ASD can easily be missed in elderly individuals presenting with comorbid psychiatric disorders, potentially causing iatrogenic damage. Although further research on phenotyping and diagnosing ASD in older people is warranted, the most important step at this point is to create a greater awareness of the possibility of ASD in old age among health-care professionals working with people in this age group.

Amygdala and hippocampus enlargement during adolescence in autism.

OBJECTIVE: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse. METHOD: We measured amygdala and hippocampus volume in a homogeneous group of adolescents with autism (12 through 18 years; n = 23) and compared them with an age-, sex-, and IQ-matched control group (n = 29) using a validated automated segmentation procedure in 1.5-T magnetic resonance images. All analyses were adjusted for total brain volume. RESULTS: Repeated-measures analysis revealed a significant group x hemisphere x brain structure interaction (p = .038), even when corrected for total brain volume. Post-hoc analysis showed that the right amygdala and left hippocampus were significantly enlarged (p = .010; p = .015) in the autism compared with the control group. There were no significant correlations between age and amygdala or hippocampus volume. CONCLUSIONS: The abnormal enlargement of the amygdala and hippocampus in adolescents with autism adds to previous findings of enlargement of these structures in children with autism. This may reflect increased activity of these structures and thereby altered emotion perception and regulation. Our results could therefore be interpreted in light of developmental adaptation of the autistic brain to a continuous overflow of emotional learning experiences.

Impaired task switching performance in children with dyslexia but not in children with autism.

Problems with cognitive control in both autism and dyslexia have already been reported in different studies. The present study specifically examined task-switching performance in children with autism and dyslexia. For this purpose, a multiple-trial paradigm was used with cues for colour- and shape-matching tasks presented before a run of trials. The cue could imply a task switch (when the cue changed the task) or a task repetition (when the cue did not change the task). Both reaction times and error rates were measured for switching, restarting, and general task performance. Participants were children with autism (24) and with dyslexia (25) and healthy controls (27) with normal IQ and ages from 12 to 18 years. The main finding was that while similar switching performance was observed between children with autism and the healthy controls, children with dyslexia showed a significant switch-specific delay relative to both healthy controls and children with autism. Furthermore, no deficit in restarting performance was observed for any of the two patient groups. Finally, additional evidence is provided for a more general deficit in information processing in dyslexia. Our data suggest that children with autism are able to switch between tasks in a similar way as do normally developing children as long as the tasks are unambiguously specified. Furthermore, the data imply switch-specific deficits in dyslexia additionally to the deficits in general information processing already reported in the literature. The implications of our data are further discussed in relation to the interpretation of the Wisconsin Card Sorting Test.

Intact spectral but abnormal temporal processing of auditory stimuli in autism.

The perceptual pattern in autism has been related to either a specific localized processing deficit or a pathway-independent, complexity-specific anomaly. We examined auditory perception in autism using an auditory disembedding task that required spectral and temporal integration. 23 children with high-functioning-autism and 23 matched controls participated. Participants were presented with two-syllable words embedded in various auditory backgrounds (pink noise, moving ripple, amplitude-modulated pink noise, amplitude-modulated moving ripple) to assess speech-in-noise-reception thresholds. The gain in signal perception of pink noise with temporal dips relative to pink noise without temporal dips was smaller in children with autism (p = 0.008). Thus, the autism group was less able to integrate auditory information present in temporal dips in background sound, supporting the complexity-specific perceptual account.

[Pseudologia fantastica. Recognition and treatment of pathological lying]. / Pseudologica fantastica: herkenning en behandeling van pathologisch liegen.

Although a clear definition of pseudologia fantastica cannot be found in the literature, there is consensus that this condition differs quantitatively and qualitatively from 'normal lying'. We discuss recognition of pseudologia fantastica based on 2 patients who presented with suicidal ideations at the casualty department following a traumatic event. Early recognition is important in order to break the pattern of lying, to restrict the use of medical resources and, finally, to act in accordance with the general principle of 'primum-non-nocere'. Although a psychiatric diagnostic workup might be worthwhile, it remains difficult to engage these patients for psychiatric treatment.

The phenotype and neural correlates of language in autism: an integrative review.

Although impaired communication is one of the defining criteria in autism, linguistic functioning is highly variable among people with this disorder. Accumulating evidence shows that language impairments in autism are more extensive than commonly assumed and described by formal diagnostic criteria and are apparent at various levels. Phenotypically, most people with autism have semantic, syntactic and pragmatic deficits, a smaller number are known to have phonological deficits. Neurophysiologically, abnormal processing of low-level linguistic information points to perceptual difficulties. Also, abnormal high-level linguistic processing of the frontal and temporal language association cortices indicates more self-reliant and less connected neural subsystems. Early sensory impairments and subsequent atypical neural connectivity are likely to play a part in abnormal language acquisition in autism. This paper aims to review the available data on the phenotype of language in autism as well as a number of structural, electrophysiological and functional brain-imaging studies to provide a more integrated view of the linguistic phenotype and its underlying neural deficits, and to provide new directions for research and therapeutic and experimental applications.

Gender in voice perception in autism.

Deficits in the perception of social stimuli may contribute to the characteristic impairments in social interaction in high functioning autism (HFA). Although the cortical processing of voice is abnormal in HFA, it is unclear whether this gives rise to impairments in the perception of voice gender. About 20 children with HFA and 20 matched controls were presented with voice fragments that were parametrically morphed in gender. No differences were found in the perception of gender between the two groups of participants, but response times differed significantly. The results suggest that the perception of voice gender is not impaired in HFA, which is consistent with behavioral findings of an unimpaired voice-based identification of age and identity by individuals with autism. The differences in response times suggest that individuals with HFA use different perceptual approaches from those used by typically developing individuals.