Typically Developing Controls Research Articles

The Association Between Gastrointestinal Issues and Psychometric Scores in Children with Autism Spectrum Disorder, Developmental Delays, Down Syndrome, and Typical Development.

Investigate the association between gastrointestinal (GI) issues and psychometric scores among children with developmental delays and typical development. We examined the association between GI issues and the Mullen Scale of Early Learning (MSEL), Vineland Adaptive Behavior Subscales (VABS), and Aberrant Behavior Checklist (ABC) scores from participants with autism spectrum disorder (ASD), Down syndrome (DS),other developmental delays (DD) and typical development (TD) from the CHildhood Autism Risk from Genetics and Environment (CHARGE) Study (n = 1603). Approximately 32% of children with ASD, 31% of children with DD, and 20% of children with DS reported at least one GI issue, compared to 7% of TD controls.Constipation was the most frequently reported symptom for the entire population, including controls. In general, GI issues correlated with poorer behavioral scores (decreased communication, daily living, socialization, and motor skills on the VABS, and increased irritability/agitation, lethargy/social withdrawal, stereotypic behavior, and hyperactivity/noncompliance on the ABC) among ASD cases. Analysis by sex indicated that GI issues also correlated with poorer cognitive scores (fine motor, receptive language, expressive language, and MSEL composite scores), and adaptive behavior (communication skills, daily living skills, motor, and VABS composite scores) among boys with DD, but not girls with DD-suggesting sex differences among DD cases. Even TD controls showed increased stereotypic behavior and social withdrawal in association with GI issues. However, GI issues were not correlated with impairments in psychometric scores among DS cases. Given that GI issues correlate with deficits in behavioral and cognitive scores, future studies should investigate the treatment of GI symptoms in children with ASD and DD.

Challenges with computing scalar and ad-hoc implicatures in Mandarin-speaking 4–8-year-old autistic children

IntroductionMixed findings have been reported about the computation of scalar or/and ad-hoc implicatures in primarily school-age autistic verbal children and adolescents: while some studies reported their struggles with both implicatures, others observed their strengths in computing scalar implicatures. This study extends the previous investigation by testing the derivation of scalar (including both number and quantifier) and ad-hoc implicatures of a younger group of Mandarin-speaking autistic 4–8-year-olds; moreover, we assess the biological, linguistic, and cognitive factors affecting children's implicature acquisition. MethodsThe participants included 22 4–8-year-old autistic verbal children (mean age = 67.64 months) and 19 typically developing (TD) children who did not significantly differ in age, receptive vocabulary, and non-verbal IQ. Both groups completed a computer-based Truth Value Judgment task, assessing their knowledge of scalar (involving the number ‘three’ and the quantifier ‘some’) and ad-hoc implicatures. We also examined whether their implicature computation was linked to age, receptive vocabulary, non-verbal IQ, and Theory of Mind (ToM). ResultsCompared with the TD controls, autistic children derived significantly fewer scalar and ad-hoc implicatures. Specifically, TD children successfully computed number and ad-hoc implicatures, contrasting to the bimodal distribution of their pragmatic vs. logical responses to quantifier implicatures. Though autistic children performed better with number implicatures slightly above the chance level, they had difficulties in computing quantifier and ad-hoc implicatures. Further, autistic children's knowledge of the number and ad-hoc implicatures was linked to their ToM skills. ConclusionsThese findings underscore the overall delayed implicature knowledge of young autistic children, and their low sensitivity to the implicatures is related to the core ToM deficits. Furthermore, our data confirm the coherent pattern of the earlier acquisition of number over quantifier implicatures and illuminate the distinct mechanisms underlying the computation of scalar vs. ad-hoc implicatures.

The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives

BackgroundMost children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance.MethodsWe used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals.ResultsFirst, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills.LimitationsWe only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis.ConclusionsAutistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles.

Assessing Frontal Lobe Function on Verbal Fluency and Emotion Recall in Autism Spectrum Disorder by fNIRS.

This study applied the functional near-infrared spectroscopy (fNIRS) to investigate frontal activity in autism when performing verbal fluency test and emotion recall task. We recruited 32 autistic adults without intellectual disability and 30 typically-developing controls (TDC). Prefrontal hemodynamic changes were evaluated by fNIRS when the participants performed the verbal fluency test and emotion recall task. fNIRS signals in the prefrontal cortex were compared between autism and TDC. Compared to TDC, autistic adults showed comparable performance on the verbal fluency test but exhibited lower frontal activity on the vegetable category. In the verbal fluency test, left frontal activity in TDC significantly increased in the vegetable category (vs. fruit category). In the emotion recall task, left frontal activity increased significantly in TDC when recalling emotional (vs. neutral) events. This increase of left frontal activity on the more difficult works was not found in autism. Similarly, brain activities were related to test performance only in TDC but not in autism. In addition, more severe social deficits were associated with lower frontal activity when recalling emotional events, independent of autism diagnosis. Findings suggested reduced frontal activity in autism, as compared to TDC, when performing verbal fluency tests. The reduction of left frontal activation in verbal fluency test and emotion recall tasks might reflect on the social deficits of the individual. The fNIRS may potentially be applied in assessing frontal lobe function in autism and social deficits in general population. Trial registration number: NCT04010409.

Attention toward Social and Non-Social Stimuli in Preschool Children with Autism Spectrum Disorder: A Paired Preference Eye-Tracking Study.

Different dimensions of visual attention to social (human faces) and non-social stimuli (objects) were assessed in 19 preschool children with Autism Spectrum Disorder (ASD) and 19 typically developing (TD) age, gender, and IQ-matched controls through an original paired preference eye-tracking paradigm. The present study found a significantly reduced attentional bias toward human faces in children with ASD compared to TD controls. The analysis of the total fixation time showed a significantly reduced preference for faces in children with ASD compared to TD children. Moreover, while TD children showed a significant preference for the face over the object, children in the ASD group observed the two paired pictures for a similar amount of time, thus showing no preference. Besides, children with ASD paid significantly more sustained attention to the objects than TD children. Children in the TD group paid greater sustained attention to the faces over the objects, while children in the ASD group did not differentiate between objects and faces. Finally, an age effect was found in ASD, as younger children in the group tended to prefer objects and to show more sustained attention towards them. Overall, these findings add to the literature on anomalies in attention toward social and non-social stimuli in young children with ASD compared to their TD counterparts. These results are discussed in the light of previous studies and suggest possible directions for future research.

Muscle synergy-informed neuromusculoskeletal modelling to estimate knee contact forces in children with cerebral palsy.

Cerebral palsy (CP) includes a group of neurological conditions caused by damage to the developing brain, resulting in maladaptive alterations of muscle coordination and movement. Estimates of joint moments and contact forces during locomotion are important to establish the trajectory of disease progression and plan appropriate surgical interventions in children with CP. Joint moments and contact forces can be estimated using electromyogram (EMG)-informed neuromusculoskeletal models, but a reduced number of EMG sensors would facilitate translation of these computational methods to clinics. This study developed and evaluated a muscle synergy-informed neuromusculoskeletal modelling approach using EMG recordings from three to four muscles to estimate joint moments and knee contact forces of children with CP and typically developing (TD) children during walking. Using only three to four experimental EMG sensors attached to a single leg and leveraging an EMG database of walking data of TD children, the synergy-informed approach estimated total knee contact forces comparable to those estimated by EMG-assisted approaches that used 13 EMG sensors (children with CP, n = 3, R2 = 0.95 ± 0.01, RMSE = 0.40 ± 0.14 BW; TD controls, n = 3, R2 = 0.93 ± 0.07, RMSE = 0.19 ± 0.05 BW). The proposed synergy-informed neuromusculoskeletal modelling approach could enable rapid evaluation of joint biomechanics in children with unimpaired and impaired motor control within a clinical environment.

Common and distinct cortical thickness alterations in youth with autism spectrum disorder and attention-deficit/hyperactivity disorder

BackgroundAutism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with overlapping behavioral features and genetic etiology. While brain cortical thickness (CTh) alterations have been reported in ASD and ADHD separately, the degree to which ASD and ADHD are associated with common and distinct patterns of CTh changes is unclear.MethodsWe searched PubMed, Web of Science, Embase, and Science Direct from inception to 8 December 2023 and included studies of cortical thickness comparing youth (age less than 18) with ASD or ADHD with typically developing controls (TDC). We conducted a comparative meta-analysis of vertex-based studies to identify common and distinct CTh alterations in ASD and ADHD.ResultsTwelve ASD datasets involving 458 individuals with ASD and 10 ADHD datasets involving 383 individuals with ADHD were included in the analysis. Compared to TDC, ASD showed increased CTh in bilateral superior frontal gyrus, left middle temporal gyrus, and right superior parietal lobule (SPL) and decreased CTh in right temporoparietal junction (TPJ). ADHD showed decreased CTh in bilateral precentral gyri, right postcentral gyrus, and right TPJ relative to TDC. Conjunction analysis showed both disorders shared reduced TPJ CTh located in default mode network (DMN). Comparative analyses indicated ASD had greater CTh in right SPL and TPJ located in dorsal attention network and thinner CTh in right TPJ located in ventral attention network than ADHD.ConclusionsThese results suggest shared thinner TPJ located in DMN is an overlapping neurobiological feature of ASD and ADHD. This alteration together with SPL alterations might be related to altered biological motion processing in ASD, while abnormalities in sensorimotor systems may contribute to behavioral control problems in ADHD. The disorder-specific thinner TPJ located in disparate attention networks provides novel insight into distinct symptoms of attentional deficits associated with the two neurodevelopmental disorders.Trial registrationPROSPERO CRD42022370620. Registered on November 9, 2022.

Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations.

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in a total of 385 scans from 22qDel (n = 96, scans = 191, 53.1% female), 22qDup (n = 37, scans = 64, 45.9% female), and TD controls (n = 80, scans = 130, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the linear effects of 22q11.2 gene dosage and non-linear effects of age were characterized with generalized additive mixed models (GAMMs). Positive gene dosage effects (volume increasing with copy number) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.

Stimulant medications in children with ADHD normalize the structure of brain regions associated with attention and reward.

Children with ADHD show abnormal brain function and structure. Neuroimaging studies found that stimulant medications may improve brain structural abnormalities in children with ADHD. However, prior studies on this topic were conducted with relatively small sample sizes and wide age ranges and showed inconsistent results. In this cross-sectional study, we employed latent class analysis and linear mixed-effects models to estimate the impact of stimulant medications using demographic, clinical measures, and brain structure in a large and diverse sample of children aged 9-11 from the Adolescent Brain and Cognitive Development Study. We studied 273 children with low ADHD symptoms and received stimulant medication (Stim Low-ADHD), 1002 children with high ADHD symptoms and received no medications (No-Med ADHD), and 5378 typically developing controls (TDC). After controlling for the covariates, compared to Stim Low-ADHD and TDC, No-Med ADHD showed lower cortical thickness in the right insula (INS, d = 0.340, PFDR = 0.003) and subcortical volume in the left nucleus accumbens (NAc, d = 0.371, PFDR = 0.003), indicating that high ADHD symptoms were associated with structural abnormalities in these brain regions. In addition, there was no difference in brain structural measures between Stim Low-ADHD and TDC children, suggesting that the stimulant effects improved both ADHD symptoms and ADHD-associated brain structural abnormalities. These findings together suggested that children with ADHD appear to have structural abnormalities in brain regions associated with saliency and reward processing, and treatment with stimulant medications not only improve the ADHD symptoms but also normalized these brain structural abnormalities.

Assessing the impact of infantile hydrocephalus on visuomotor integration through behavioural and neuroimaging studies

ABSTRACT Infantile hydrocephalus considerably impacts neurodevelopment, warranting attention to potential long-term consequences on visuomotor functions. The current study investigated the impact of infantile hydrocephalus on functional connectivity within the posterior cortex. Fourteen patients, who were treated for infantile hydrocephalus, were matched for age and sex with 14 typically-developing controls. Both groups had a mean age of 9 years old. Resting-state functional MRI was used to conduct a functional connectivity analysis within the visuomotor integration network, including the inferior frontal occipital fasciculus, superior longitudinal fasciculus, and frontal aslant tract. Patients had reduced functional connectivity in visuomotor pathways compared to typically-developing children with notable impact on the left and right fusiform gyrus and precuneus. Children with infantile hydrocephalus also performed significantly lower in tasks involving visuomotor integration, visual processing, visuospatial skills, motor coordination, and fine motor manipulation. This study enhances our understanding of the multifaceted impact of infantile hydrocephalus on both neural connectivity and considering behavioral outcomes.

Gait Characterization in Duchenne Muscular Dystrophy (DMD) Using a Single-Sensor Accelerometer: Classical Machine Learning and Deep Learning Approaches.

Differences in gait patterns of children with Duchenne muscular dystrophy (DMD) and typically developing (TD) peers are visible to the eye, but quantifications of those differences outside of the gait laboratory have been elusive. In this work, we measured vertical, mediolateral, and anteroposterior acceleration using a waist-worn iPhone accelerometer during ambulation across a typical range of velocities. Fifteen TD and fifteen DMD children from 3 to 16 years of age underwent eight walking/running activities, including five 25 m walk/run speed-calibration tests at a slow walk to running speeds (SC-L1 to SC-L5), a 6-min walk test (6MWT), a 100 m fast walk/jog/run (100MRW), and a free walk (FW). For clinical anchoring purposes, participants completed a Northstar Ambulatory Assessment (NSAA). We extracted temporospatial gait clinical features (CFs) and applied multiple machine learning (ML) approaches to differentiate between DMD and TD children using extracted temporospatial gait CFs and raw data. Extracted temporospatial gait CFs showed reduced step length and a greater mediolateral component of total power (TP) consistent with shorter strides and Trendelenberg-like gait commonly observed in DMD. ML approaches using temporospatial gait CFs and raw data varied in effectiveness at differentiating between DMD and TD controls at different speeds, with an accuracy of up to 100%. We demonstrate that by using ML with accelerometer data from a consumer-grade smartphone, we can capture DMD-associated gait characteristics in toddlers to teens.

The production of relative clauses in Italian-speaking children with DLD

Children with Developmental Language Disorder (DLD) have been shown to struggle with the acquisition of complex structures requiring structural embedding and movement of a sentential element from its original position. This study examines the production of subject and object relative clauses (RCs) by Italian children, investigating whether: i) seven-year-old children with DLD are impaired in embedding or movement operations; ii) specific factors, such as animacy of the arguments, affect the production of sentences with movement and embedding, iii) the linguistic profile of children with DLD is qualitatively different from that of typically developing (TD) children. We elicited the production of RCs with animate and inanimate arguments in 12 Italian-speaking children with DLD (mean age = 7;2) and in two TD control groups: age matched (AM) and language matched (LM). Children with DLD produced fewer RCs than either control group and made different errors, showing a slightly different developmental path. Animacy mismatch did not improve RC production in any group. Results suggest that seven-year-old children with DLD are in a transitional stage: they can use embedding but still have difficulties with movement operations, especially in object RCs. This indicates that the language competence of children with DLD improves with age, but long-distance dependencies continue to be challenging.

Neurochemical differences in core regions of the autistic brain: a multivoxel 1H-MRS study in children

Autism spectrum disorder (ASD) is a neurodevelopmental condition which compromises various cognitive and behavioural domains. The understanding of the pathophysiology and molecular neurobiology of ASD is still an open critical research question. Here, we aimed to address ASD neurochemistry in the same time point at key regions that have been associated with its pathophysiology: the insula, hippocampus, putamen and thalamus. We conducted a multivoxel proton magnetic resonance spectroscopy (1H-MRS) study to non-invasively estimate the concentrations of total choline (GPC + PCh, tCho), total N-acetyl-aspartate (NAA + NAAG, tNAA) and Glx (Glu + Gln), presenting the results as ratios to total creatine while investigating replication for ratios to total choline as a secondary analysis. Twenty-two male children aged between 10 and 18 years diagnosed with ASD (none with intellectual disability, in spite of the expected lower IQ) and 22 age- and gender-matched typically developing (TD) controls were included. Aspartate ratios were significantly lower in the insula (tNAA/tCr: p = 0.010; tNAA/tCho: p = 0.012) and putamen (tNAA/tCr: p = 0.015) of ASD individuals in comparison with TD controls. The Glx ratios were significantly higher in the hippocampus of the ASD group (Glx/tCr: p = 0.027; Glx/tCho: p = 0.011). Differences in tNAA and Glx indices suggest that these metabolites might be neurochemical markers of region-specific atypical metabolism in ASD children, with a potential contribution for future advances in clinical monitoring and treatment.

Volume-based and Surface-Based Methods in Autism Compared with Healthy Controls Are Free surfer and CAT12 in Agreement?

Autism Spectrum Disorder (ASD) encompasses a range of neurodevelopmental disorders, and early detection is crucial. This study aims to identify the Regions of Interest (ROIs) with significant differences between healthy controls and individuals with autism, as well as evaluate the agreement between FreeSurfer 6 (FS6) and Computational Anatomy Toolbox (CAT12) methods. Surface-based and volume-based features were extracted from FS software and CAT12 toolbox for Statistical Parametric Mapping (SPM) software to estimate ROI-wise biomarkers. These biomarkers were compared between 18 males Typically Developing Controls (TDCs) and 40 male subjects with ASD to assess group differences for each method. Finally, agreement and regression analyses were performed between the two methods for TDCs and ASD groups. Both methods revealed ROIs with significant differences for each parameter. The Analysis of Covariance (ANCOVA) showed that both TDCs and ASD groups indicated a significant relationship between the two methods (p<0.001). The R2 values for TDCs and ASD groups were 0.692 and 0.680, respectively, demonstrating a moderate correlation between CAT12 and FS6. Bland-Altman graphs showed a moderate level of agreement between the two methods. The moderate correlation and agreement between CAT12 and FS6 suggest that while some consistency is observed in the results, CAT12 is not a superior substitute for FS6 software. Further research is needed to identify a potential replacement for this method.

Delineating the impact of childhood traumatic brain injury (TBI) on long-term depressive symptom severity: Does sub-acute brain morphometry prospectively predict 2-year outcome?

Despite evidence of a link between childhood TBI and heightened risk for depressive symptoms, very few studies have examined early risk factors that predict the presence and severity of post-injury depression beyond 1-year post injury. This longitudinal prospective study examined the effect of mild-severe childhood TBI on depressive symptom severity at 2-years post-injury. It also evaluated the potential role of sub-acute brain morphometry and executive function (EF) in prospectively predicting these long-term outcomes. The study involved 81 children and adolescents with TBI, and 40 age-and-sex matched typically developing (TD) controls. Participants underwent high-resolution structural magnetic resonance imaging (MRI) sub-acutely at five weeks post-injury (M = 5.55; SD = 3.05 weeks) and EF assessments were completed at 6-months post-injury. Compared to TD controls, the TBI group had significantly higher overall internalizing symptoms and were significantly more likely to exhibit clinically significant depressive symptoms at 2-year follow-up. The TBI group also displayed significantly lower EF and altered sub-acute brain morphometry in EF-related brain networks, including the default-mode network (DMN), salience network (SN) and central executive network (CEN). Mediation analyses revealed significant indirect effects of CEN morphometry on depression symptom severity, such that lower EF mediated the prospective association between altered CEN morphometry and higher depression symptoms in the TBI group. Parallel mediation analyses including grey matter morphometry of a non-EF brain network (i.e., the mentalising network) were not statistically significant, suggesting some model specificity. The findings indicate that screening for early neurostructural and neurocognitive risk factors may help identify children at elevated risk of depressive symptoms following TBI. For instance, children at greatest risk of post-injury depression symptoms could be identified based in part on neuroimaging of networks implicated in EF and post-acute assessments of executive function, which could support more effective allocation of limited intervention resources.

Gray matter asymmetry alterations in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder.

Despite the high coexistence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) (ASD + ADHD), the underlying neurobiologicalbasis of this disorder remains unclear. Altered brain structural asymmetries have been verified in ASD and ADHD, respectively, making brain asymmetry a candidate for characterizing this coexisting disorder. Here, we measured the gray matter (GM) volume asymmetry in ASD + ADHD versus ASD without ADHD (ASD-only), ADHD without ASD (ADHD-only), and typically developing controls (TDc). High-resolutionT1-weighted data from 48 ASD + ADHD, 63 ASD-only, 32 ADHD-only, and 211 matched TDc were included in our study. We also assessed brain-behavior relationships and the effects of age on GM asymmetry. We found that there were both shared and disorder-specific GM volume asymmetry alterations in ASD + ADHD, ASD-only, and ADHD-only compared with TDc. This finding demonstrates that ASD + ADHD is neither an endophenocopy nor an additive pathology of ASD and ADHD, but an entirely different neuroanatomical pathology. In addition, ASD + ADHD displayed altered GM volume asymmetries in the prefrontal regions responsible for executive function and theory of mind compared with ASD-only. We also found significant effects of age on GM asymmetry. The present study may provide structural insights into the neural basis of ASD + ADHD.

Impaired segregation of the attention deficit hyperactivity disorder related pattern in children

BackgroundInattention is a key characteristic of attention deficit hyperactivity disorder (ADHD). Specific brain abnormalities associated with this symptom form a discernible pattern related with ADHD in children (i.e., ADHD related pattern) in our earlier research. The developmental processes of segregation and integration may be crucial to ADHD. However, how brains reconfigure these processes of the ADHD related pattern in different subtypes of ADHD and across sexes remain unclear. MethodsNested-spectral partition method was applied to identify effects of subtype and sex on segregation and integration of the ADHD related pattern, using 145 ADHD patients and 135 typically developing controls (TDC) aged 7–14. Relationships between the measures and inattention symptoms were also investigated. ResultsChildren with ADHD exhibited lower segregation of the ADHD related pattern (p = 1.17 × 10−8) than TDCs. Only the main effect of subtype was significant (p = 1.14 × 10−5). Both ADHD-C (p = 2.16 × 10−6) and ADHD-I (p = 2.87 × 10−6) patients had lower segregation components relative to the TDC. Moreover, segregation components were negatively correlated with inattention scores. ConclusionsThis study identified impaired segregation in the ADHD related pattern of children with ADHD and found shared neural bases among different subtypes and sexes.

Distinct developmental changes in regional gray matter volume and covariance in individuals with attention-deficit hyperactivity disorder: A longitudinal voxel-based morphometry study

BackgroundVery few studies have investigated longitudinal clinical cohorts of attention-deficit/hyperactivity disorder (ADHD). Moreover, how baseline brain changes could affect the development of ADHD symptoms later in life remains elusive. Therefore, we aimed to fill this gap by exploring brain and clinical changes in youth with ADHD using a longitudinal design. MethodsThis prospective study consisted of 74 children and adolescents with ADHD and 50 age-, sex-, intelligence-matched typically developing controls (TDC), evaluated at baseline (aged 7–19 years) and re-evaluated 5.3 years later (a mean follow-up latency). We applied voxel-based morphometry to characterize brain structures, followed by both mass-univariate and multivariate structural covariance statistics to identify brain regions with significant diagnosis-by-time interactions from late childhood/adolescence to early adulthood. We used the cross-lagged panel model to investigate the longitudinal association between structural brain metrics and core ADHD symptoms. ResultsThe mass-univariate statistic revealed significant diagnosis-by-time interactions in the right striatum and the sixth lobule of the cerebellum. This was expressed by increased striatal and decreased cerebellar volume in ADHD, while TDC showed inverse volume changes over time. The multivariate method showed significant diagnosis-by-time interactions in a structural covariance network consisting of the regions involved in the functional sensory-motor and default-mode networks. Higher baseline right striatal and cerebellar volumes were associated with elevated ADHD symptoms at follow-up. ConclusionsOur findings suggest a temporal association between the divergent development of striatal and cerebellar regions and dynamical ADHD phenotypic expression through young adulthood. These results highlight a potential brain marker of future outcomes.

Corneal structural alterations in autism spectrum disorder: An in vivo confocal microscopy study.

Individuals with autism spectrum disorder (ASD) often exhibit joint hypermobility and connective tissue disorders. However, it remains unclear if ASD individuals also have structural alterations in the connective tissue of the cornea. This study aims to determine whether the Kobayashi structure (K-structure) characteristics differ between adults with ASD and typically developing controls (TDC) and explore the clinical correlates of the K-structure abnormality. We recruited 30 ASD adults and 35 TDC. Corneal structures, particularly the K-structure in the Bowman's layer, of the participants were examined using in vivo confocal microscopy (IVCM), and a K-grading ranging from 1 to 4 was given to each eye based on the level of morphological mosaicism. The ASD participants' eyes received a significantly higher single-eye K-grading than that of the TDC eyes (p < 0.001), and the medians [25th, 75th percentile] of bilateral-eye summed K-grading were 8 [7, 8] and 5 [4, 6] in ASD and TDC, respectively (p < 0.001). A significantly higher K-grading in the ASD participants' eyes was still observed after adjusting for the within-subject inter-eye correlation (p < 0.001). Youden Index showed the optimal cutoffs to differentiate ASD from TDC by bilateral-eye summed K-grading and single-eye K-grading was >6 and >3, respectively. Additionally, a higher K-grading was associated with fewer visual sensation seeking in ASD (Spearman's correlation coefficient ρ = -0.518, p = 0.008) and low visual registration (i.e., higher sensory threshold) in TDC (ρ = 0.446, p = 0.023). This study provided novel evidence of corneal structural alterations in ASD by IVCM. Our findings may not only support the prior hypothesis of the association between ASD and connective tissue abnormalities but also shed light on the relationship between connective tissue disorder and neurodevelopmental disorders.

A Cross-sectional Conceptual Replication and Longitudinal Evaluation of the PANSS-Autism-Severity-Score Measure Suggests it Does Not Capture Autistic Traits in Individuals With Psychosis.

Autism and psychosis co-occur at elevated rates, with implications for clinical outcomes, functioning, and suicidality. The PANSS-Autism-Severity-Score (PAUSS) is a measure of autism trait severity which has not yet been validated externally or longitudinally. Participants were derived from the GROUP and SCOPE datasets. Participants included 1448 adults with schizophrenia spectrum disorder (SSD), 800 SSD-siblings, 103 adults diagnosed with an autistic spectrum condition (ASC), and 409 typically-developing controls (TC). Analyses from the original validation study were conducted with SSD participants, and extended into ASC, SSD-sibling, and TC participants. Test-retest reliability of the PAUSS at 2-weeks and long-term stability 3 and 6-years was also examined. Results differed in important ways from the original validation. SSD participants reported higher PAUSS scores than other groups, with only a fraction of ASC participants scoring as "PAUSS-Autistic." Cronbach's alpha was acceptable for the SSD cohort only. Two-week stability of the PAUSS was fair to good for all PAUSS scores. Long-term stability was poor for most PAUSS items but fair for total PAUSS score. Results suggest that the PAUSS does not appear appropriate for assessing autism, with the low rate of PAUSS-Autistic in the ASC population suggesting the PAUSS may not accurately reflect characteristics of autism. The relative lack of long-term stability is cause for concern and suggestive that the PAUSS is capturing features of psychosis rather than autism traits.