To Typically Developing Controls Research Articles

Correlation of altered intrinsic functional connectivity with impaired self-regulation in children and adolescents with ADHD.

Attention-deficit hyperactivity disorder (ADHD) has a high prevalence of co-occurring impaired self-regulation (dysregulation), exacerbating adverse outcomes. Neural correlates underlying impaired self-regulation in ADHD remain inconclusive. We aimed to investigate the impact of dysregulation on intrinsic functional connectivity (iFC) in children with ADHD and the correlation of iFC with dysregulation among children with ADHD relative to typically developing controls (TDC). Resting-state functional MRI data of 71 children with ADHD (11.38 ± 2.44years) and 117 age-matched TDC were used in the final analysis. We restricted our analyses to resting-state networks (RSNs) of interest derived from independent component analysis. Impaired self-regulation was estimated based on the Child Behavioral Checklist-Dysregulation Profile. Children with ADHD showed stronger iFC than TDC in the left frontoparietal network, somatomotor network (SMN), visual network (VIS), default-mode network (DMN), and dorsal attention network (DAN) (FWE-corrected alpha < 0.05). After adding dysregulation levels as an extra regressor, the ADHD group only showed stronger iFC in the VIS and SMN. ADHD children with high dysregulation had higher precuneus iFC within DMN than ADHD children with low dysregulation. Angular gyrus iFC within DMN was positively correlated with dysregulation in the ADHD group but negatively correlated with dysregulation in the TDC group. Functional network connectivity showed ADHD had a greater DMN-DAN connection than TDC, regardless of the dysregulation level. Our findings suggest that DMN connectivity may contribute to impaired self-regulation in ADHD. Impaired self-regulation should be considered categorical and dimensional moderators for the neural correlates of altered iFC in ADHD.

21 Nonverbal Assessment of Theory of Mind in Children with Down Syndrome and Typically Developing Peers: An Examination of Group Differences and Associations with Structural Language Skills

Objective:Children with Down syndrome (DS) show marked differences in their early development when compared to typically developing (TD) peers. Major domains of challenge include intellectual abilities, executive functioning, and structural language. Children with DS have a unique profile of strengths and weaknesses that must be considered when comparing them to TD children, especially in terms of Theory of Mind (ToM). ToM encompasses the developmental milestones reached early in childhood when children develop the ability to conceptualize and understand others' thoughts, emotions, perspectives, and intentions. In TD children, these abilities typically begin to mature around 4-6 years of age, while in children with DS, delays are observed relative to chronological age expectations. Evidence shows that children with DS have impaired ToM abilities; however, these deficits might be more related to underlying delays in structural language, rather than a fundamental misunderstanding of social cues. The present study seeks to fill gaps in the literature by using a nonverbal assessment (The Penny Hiding Game; PHG) to evaluate a) ToM abilities in children with DS relative to younger TD peers of a similar mental ability level and b) relationships between ToM performance and structural language skills.Participants and Methods:25 children with DS (60% F, M=11.39 years) and 25 TD children (40% F, M = 5.37, range = 3 to 7) participated. Participants' structural language abilities were briefly assessed using the Wechsler Individual Achievement Test- III Listening Comprehension Test (Oral Discourse Comprehension subcomponent). ToM was assessed using the PHG.Results:Univariate analysis of covariance was used to explore differences in ToM performance between groups while controlling for mental ability level. Children with DS (M= 2.79, SD= 2.23) performed significantly worse than TD peers (M= 4.28, SD= 1.87) on the ToM task (F(1, 60)= 4.5, p= .038). Linear regression was used to assess associations between ToM and structural language abilities. When both groups were lumped together, there was a modest association between ToM and Listening Comprehension scores (R2 = .12, F (1, 55) = 7.29, p= .009). However, when groups were considered separately, significant associations were not observed (p&gt;.1).Conclusions:The DS group showed markedly diminished ToM performance compared to TD controls, as expected based on the literature. However, data did not suggest a clear association between ToM and structural language skills. While an association was observed when groups were lumped, this relationship was likely driven by group differences in both ToM and structural language skills. Future research should examine the relationship between ToM performance, different aspects of language functioning, and the cooccurrence of autistic traits among children with DS in order to augment our understanding of linguistic and social correlates of ToM performance in young children with DS.

B - 01 Children with ADHD Demonstrate Cortical Thinning in Multiple Regions Compared to TD Controls.

Children with Attention-Deficit/Hyperactivity Disorder (ADHD) often demonstrate functional and volumetric differences compared to typically developing (TD) children. These regions are associated with the deficits commonly seen in ADHD. However, there is limited research on cortical thickness in ADHD, and what does exist is inconsistent in its findings. Thus, the objective of this study was to examine potential differences in cortical thickness between children with ADHD and TD controls. Participants included 73 children (aged 8-12years; 50.7% boys, 87.7% White) with ADHD and typically developing controls. It was a community sample. The children completed an MRI scan and a neuropsychological battery as part of a larger, grant-funded project (R03HD048752, R15HD065627). Group differences in cortical thickness were determined using CAT12 software. A t-test model was used for voxel-wise comparisons of cortical thickness between children with ADHD and TD controls. After aligning the MRI scans, the CAT12 software provides clusters of regions in which cortical thickness differs significantly between groups. Compared with TD controls, children with ADHD demonstrated reduced cortical thickness in three clusters in the left hemisphere and one large cluster in the right hemisphere (p < 0.05; FWE corrected). The clusters included several frontal and parietal regions, along with occipital and temporal regions. Results are consistent with findings from prior research comparing children with ADHD and TD controls using other neuroimaging methods, which displayed involvement of frontal-parietal and/or frontal-temporal networks. Furthermore, these regions are associated with cognitive and behavioral deficits commonly seen in ADHD, including various aspects of executive dysfunction.

Upregulation of Inflammatory Mediators in Peripheral Blood CD40+ Cells in Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a common and severe neurodevelopmental disorder in early childhood, defined as social and communication deficits and repetitive and stereotypic behaviours. The aetiology is unknown in most cases. However, several studies have identified immune dysregulation as potentially promoting ASD. Among the numerous immunological findings in ASD, reports of increased pro-inflammatory markers remain the most consistently observed. C-C chemokine receptor type 1 (CCR1) activation is pro-inflammatory in several neurological disorders. Previous evidence has implied that the expression of chemokine receptors, inflammatory mediators, and transcription factors play a pivotal role in several neuroinflammatory disorders. There have also been reports on the association between increased levels of proinflammatory cytokines and ASD. In this study, we aimed to investigate the possible involvement of CCR1, inflammatory mediators, and transcription factor expression in CD40+ cells in ASD compared to typically developing controls (TDC). Flow cytometry analysis was used to determine the levels of CCR1-, IFN-γ-, T-box transcription factor (T-bet-), IL-17A-, retinoid-related orphan receptor gamma t (RORγt-), IL-22- and TNF-α-expressing CD40 cells in PBMCs in children with ASD and the TDC group. We further examined the mRNA and protein expression levels of CCR1 using real-time PCR and western blot analysis. Our results revealed that children with ASD had significantly increased numbers of CD40+CCR1+, CD40+IFN-γ+, CD40+T-bet+, CD40+IL-17A+, CD40+RORγt+, CD4+IL-22+, and CD40+TNF-α+ cells compared with the TDC group. Furthermore, children with ASD had higher CCR1 mRNA and protein expression levels than those in the TDC group. These results indicate that CCR1, inflammatory mediators, and transcription factors expressed in CD40 cells play vital roles in disease progression.

Disrupted dynamic functional network connectivity in fetal alcohol spectrum disorders.

Prenatal alcohol exposure (PAE) can result in harmful and long-lasting neurodevelopmental changes. Children with PAE or a fetal alcohol spectrum disorder (FASD) have decreased white matter volume and resting-state spectral power compared to typically developing controls (TDC) and impaired resting-statestaticfunctionalconnectivity. The impact of PAE on resting-state dynamic functional network connectivity (dFNC) is unknown. Using eyes-closed and eyes-open magnetoencephalography (MEG) resting-state data, global dFNC statistics and meta-states were examined in 89 children aged 6-16 years (51 TDC, 38 with FASD). Source analyzed MEG data were used as input to group spatial independent component analysis to derive functional networks from which the dFNC was calculated. During eyes-closed, relative to TDC, participants with FASD spent a significantly longer time in state 2, typified by anticorrelation (i.e., decreased connectivity) within and between default mode network (DMN) and visual network (VN), and state 4, typified by stronger internetwork correlation. The FASD group exhibited greater dynamic fluidity and dynamic range (i.e., entered more states, changed from one meta-state to another more often, and traveled greater distances) than TDC. During eyes-open, TDC spent significantly more time in state 1, typified by positive intra- and interdomain connectivity with modest correlation within the frontal network (FN), while participants with FASD spent a larger fraction of time in state 2, typified by anticorrelation within and between DMN and VN and strong correlation within and between FN, attention network, and sensorimotor network. There are important resting-state dFNC differences between children with FASD and TDC. Participants with FASD exhibited greater dynamic fluidity and dynamic range and spent more time in states typified by anticorrelation within and between DMN and VN, and more time in a state typified by high internetwork connectivity. Taken together, these network aberrations indicate that prenatal alcohol exposure has a global effect on resting-state connectivity.

Motor Function and Physiology in Youth With Neurofibromatosis Type 1

BackgroundNeurofibromatosis type 1 (NF1) is a genetic neurocutaneous disorder commonly associated with motor and cognitive symptoms that greatly impact quality of life. Transcranial magnetic stimulation (TMS) can quantify motor cortex physiology, reflecting the basis for impaired motor function as well as, possibly, clues for mechanisms of effective treatment. We hypothesized that children with NF1 have impaired motor function and altered motor cortex physiology compared to typically developing (TD) control children and children with attention-deficit/hyperactivity disorder (ADHD). MethodsChildren aged 8-17 years with NF1 (n = 21) were compared to children aged 8-12 years with ADHD (n = 59) and TD controls (n = 88). Motor development was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS) scale. The balance of inhibition and excitation in motor cortex was assessed using the TMS measures short-interval cortical inhibition (SICI) and intracortical facilitation (ICF). Measures were compared by diagnosis and tested using bivariate correlations and regression for association with clinical characteristics. ResultsIn NF1, ADHD severity scores were intermediate between the ADHD and TD cohorts, but total PANESS scores were markedly elevated (worse) compared to both (P < 0.001). Motor cortex ICF (excitatory) was significantly lower in NF1 than in TD and ADHD (P < 0.001), but SICI (inhibitory) did not differ. However, in NF1, better PANESS scores correlated with lower SICI ratios (more inhibition; ρ = 0.62, P = 0.003) and lower ICF ratios (less excitation; ρ = 0.38, P = 0.06). ConclusionsTMS-evoked SICI and ICF may reflect processes underlying abnormal motor function in children with NF1.

Atypical development in white matter microstructures in ADHD: A longitudinal diffusion imaging study.

In cross-sectional studies, alterations in white matter microstructure are evident in children with attention-deficit/hyperactivity disorder (ADHD) but not so prominent in adults with ADHD compared to typically-developing controls (TDC). Moreover, the developmental trajectories of white matter microstructures in ADHD are unclear, given the limited longitudinal imaging studies that characterize developmental changes in ADHD vs. TDC. This longitudinal study acquired diffusion spectrum imaging (DSI) at two time points. The sample included 55 participants with ADHD and 61 TDC. The enrollment/first DSI age ranged from 7 to 18 years, with a five-year mean follow-up time. We examined time-by-diagnosis interaction on the generalized fractional anisotropy (GFA) of 45 white matter tracts, adjusting for confounding factors and correcting for multiple comparisons. We also tested whether the longitudinal changes of microstructures were associated with ADHD symptoms and attention performance in a computerized continuous performance test. Participants with ADHD showed more rapid development of GFA in the arcuate fasciculus, superior longitudinal fasciculus, frontal aslant tract, cingulum, inferior fronto-occipital fasciculus (IFOF), frontostriatal tract connecting the prefrontal cortex (FS-PFC), thalamic radiation, corticospinal tract, and corpus callosum. Within participants with ADHD, more rapid GFA increases in cingulum and FS-PFC were associated with slower decreases in inattention symptoms. In addition, in all participants, more rapid GFA increases in cingulum and IFOF were associated with greater improvement in attention performance. Our findings suggest atypical developmental trajectories of white matter tracts in ADHD, characterized by normalization and possible compensatory neuroplastic processes with age from childhood to early adulthood.

Analyzing Brain Connectivity Patterns in Participants at Music and Rest State Using EEG Signals

One of the most widely used methods for monitoring human brains is the brain computer interface. Cognitive neuroscience is a recently developed field of research that aims to comprehend how the brain reacts to various inputs. When compared to typically developing controls (TDC), intellectual and developmental disorder (IDD) is a result of altered brain connections, and the activity of the brain is examined using frequency bands. Electroencephalography (EEG), which analyses brain activity and used to compares IDD and TDC brain waves to identify anomalies. Participants are prone to experiment with rest and music states and EEG signal were recorded for analysis.

Shotgun Metagenomics Study Suggests Alteration in Sulfur Metabolism and Oxidative Stress in Children with Autism and Improvement after Microbiota Transfer Therapy

Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella (P. dentalis, P. enoeca, P. oris, P. meloninogenica), Bifidobacterium bifidum, and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.

Greater individual variability in functional brain activity during working memory performance in Schizophrenia Spectrum Disorders (SSD)

Heterogeneity has been a persistent challenge in understanding Schizophrenia Spectrum Disorders (SSD). Traditional case-control comparisons often show variable results, and may not map well onto individuals. To better understand heterogeneity and group differences in SSD compared to typically developing controls (TDC), we examined variability in functional brain activity during a working memory (WM) task with known deficits in SSD. Neuroimaging and behavioural data were extracted from two datasets collectively providing 34 TDC and 56 individuals with SSD (n = 90). Functional activity in response to an N-Back WM task (3-Back vs 1-Back) was examined between and within groups. Individual variability was calculated via the correlational distance of fMRI activity maps between participants; mean correlational distance from one participant to all others was defined as a ‘variability score’. Greater individual variability in functional activity was found in SSD compared to TDC (p = 0.00090). At the group level, a case-control comparison suggested SSD had reduced activity in task positive and task negative networks. However, when SSD were divided into high and low variability subgroups, the low variability groups showed no differences relative to TDC while the high variability group showed little activity at the group level. Our results imply prior case-control differences may be driven by a subgroup of SSD who do not show specific impairments but instead show more ‘idiosyncratic’ activity patterns. In SSD but not TDC, variability was also related to cognitive performance and age. This novel approach focusing on individual variability has important implications for understanding the neurobiology of SSD.

Receptive and expressive lexical stress in adolescents with autism

Purpose: Lexical stress abilities were investigated in individuals with autism spectrum disorder (ASD) compared to typically developing (TD) controls. We hypothesised that individuals with ASD would demonstrate atypical prosody on lexical and phrase stress tasks and are perceived by listeners as sounding unnatural. Method: A between-group study was conducted to investigate lexical stress abilities among adolescents (12–20 years) with ASD (n = 11) compared to TD controls (n = 11) matched for age and gender. Two tasks were administered to assess the ability to receptively and expressively distinguish nouns from verbs and a noun phrase from a compound noun. Receptive tasks required participants to select visual stimuli corresponding with the utterance they heard. Expressive tasks were rated using perceptual judgments of accuracy, perceptual and acoustic measurements of duration and perceptual ratings of “naturalness.” Result: Individuals with ASD performed with significantly less accuracy on all prosody tasks, significantly longer duration of utterances, and were rated as sounding “unnatural” at a significantly higher rate than controls. Conclusion: This study provides converging evidence that supports atypical prosody is influenced by longer duration of utterances and less accurate lexical and phrase stress. The clinical implications of this study support early assessment and intervention of prosodic disorders in ASD.

Examining the effects of prenatal alcohol exposure on corticothalamic connectivity: A multimodal neuroimaging study in children

Children with a fetal alcohol spectrum disorder (FASD) experience a range of cognitive and behavioral effects. Prior studies have demonstrated white matter changes in children with FASD relative to typically developing controls (TDC) and these changes relate to behavior. Our prior MEG study (Candelaria-Cook et al. 2020) demonstrated reduced alpha oscillations during rest in FASD relative to TDC and alpha power is correlated with behavior. However, little is known about how brain structure influences brain function. We hypothesized that alpha power was related to corticothalamic connectivity. Children 8–13 years of age (TDC: N = 25, FASD: N = 24) underwent rest MEG with eyes open or closed and MRI to collect structural and diffusion tensor imaging data. MEG spectral analysis was performed for sensor and source data. We estimated mean fractional anisotropy in regions of interest (ROIs) that included the corticothalamic tracts. The FASD group had reduced mean FA in three of the corticothalamic ROIs. FA in these tracts was significantly correlated with alpha power at the sensor and source level. The results support the hypothesis that integrity of the corticothalamic tracts influences cortical alpha power. Further research is needed to understand how brain structure and function influence behavior.

Visuomotor Activation of Inhibition-Processing in Pediatric Obsessive Compulsive Disorder: A Magnetoencephalography Study.

Background: Response inhibition engages the cortico-striato-thalamo-cortical (CSTC) circuit, which has been implicated in children, and youth with obsessive compulsive disorder (OCD). This study explored whether CSTC engagement during response inhibition, measured using magnetoencephalography (MEG), differed in a sample of medication-naïve youth with OCD, compared to typically developing controls (TDC).Methods: Data was analyzed in 17 medication-naïve children and youth with OCD (11.7 ± 2.2 SD years) and 13 TDC (12.6 ± 2.2 SD years). MEG was used to localize and characterize neural activity during a Go/No-Go task. Task performance on Go/No-Go conditions and regional differences in amplitude of activity during Go and No-Go condition between OCD vs. TDC were examined using two-sample t-tests. Post-hoc analysis with Bayesian t-tests was used to estimate the certainty of outcomes.Results: No differences in Go/No-Go performance were found between OCD and TDC groups. In response to the visual cue presented during the Go condition, participants with OCD showed significantly increased amplitude of activity in the primary motor (MI) cortex compared to TDC. In addition, significantly reduced amplitude of PCu was found following successful stopping to No-Go cues in OCD vs. TDC during No-Go task performance. Bayesian t-tests indicated high probability and large effect sizes for the differences in MI and PCu amplitude found between groups.Conclusion: Our preliminary study in a small medication-naïve sample extends previous work indicating intact response inhibition in pediatric OCD. While altered neural response in the current study was found during response inhibition performance in OCD, differences localized to regions outside of the CSTC. Our findings suggest that additional imaging research in medication-naïve samples is needed to clarify regional differences associated with OCD vs. influenced by medication effects, and suggest that MEG may be sensitive to detecting such differences.

Statistical Learning and the Effect of Starting Small in Developmental Dyslexia.

Purpose Impairments in statistical learning abilities of individuals with developmental dyslexia (DD) have been demonstrated in word segmentation and in visual artificial grammar learning (AGL) tasks, but so far, little attention has been devoted to the AGL abilities of this population in the acoustic verbal domain. This study aimed to test whether adolescents with dyslexia have difficulties in extracting abstract patterns from auditory sequences of nonsense syllables based on a finite state grammar relative to typically developing (TD) peers. We also tested whether incremental presentation of stimuli of different lengths (starting small) has a facilitating effect on learning complex structures in dyslexia (and in TD) as opposed to presenting strings in random order. Method Thirty-one adolescents with DD and 31 age-matched control participants completed an AGL task. Participants passively listened to acoustic sequences of nonsense syllables generated by an artificial grammar in the training phase. In the test phase, they were presented with pairs of novel grammatical and nongrammatical sequences and were required to decide which member of a sequence pair was more similar to the material heard during training. Results Performance levels and the proportion of learners were smaller in participants with DD than in the control group. While the starting small effect was nominally present both in performance levels and in the number of learners in participants with DD, but not in the group with TD, the presentation of strings in incremental order did not statistically improve learning performance in either group. Conclusion Our results suggest that (a) statistical learning of abstract sequences in the acoustic domain is less efficient in people with dyslexia than in TD controls and (b) while incremental presentation of stimuli of different length did not improve learning in our study, the observed pattern of results suggests that the effects of different training designs should be explored further in developmental disorders.

Reduced Inter-hemispheric Resting State Functional Connectivity and Its Association With Social Deficits in Autism.

Autism spectrum disorder (ASD) is an early onset developmental disorder which persists throughout life and is increasing in prevalence over the last few decades. Given its early onset and variable cognitive and emotional functional impairments, it is generally challenging to assess ASD individuals using task-based behavioral and functional MRI paradigms. Consequently, resting state functional MRI (rs-fMRI) has become a key approach for examining ASD-associated neural alterations and revealed functional alterations in large-scale brain networks relative to typically developing (TD) individuals, particularly those involved in social-cognitive and affective processes. Recent progress suggests that alterations in inter-hemispheric resting state functional connectivity (rsFC) between regions in the 2 brain hemispheres, particularly homotopic ones, may be of great importance. Here we have reviewed neuroimaging studies examining inter-hemispheric rsFC abnormities in ASD and its associations with symptom severity. As an index of inter-hemispheric functional connectivity, we have additionally reviewed previous studies on corpus callosum (CC) volumetric and fiber changes in ASD. There are converging findings on reduced inter-hemispheric (including homotopic) rsFC in large-scale brain networks particularly in posterior hubs of the default mode network, reduced volumes in the anterior and posterior CC, and on decreased FA and increased MD or RD across CC subregions. Associations between the strength of inter-hemispheric rsFC and social impairments in ASD together with their classification performance in distinguishing ASD subjects from TD controls across ages suggest that the strength of inter-hemispheric rsFC may be a more promising biomarker for assisting in ASD diagnosis than abnormalities in either brain wide rsFC or brain structure.

Abstract 53: Frontal Functional Connectivity Networks and Executive Function Following Perinatal Stroke

Perinatal stroke causes most hemiparetic cerebral palsy and a lifetime of disability with no known prevention strategies. Two types of perinatal stroke predominate, arterial ischemic stroke (AIS) and periventricular venous infarction (PVI), dictating lesion-specific differences in outcomes. Executive functioning challenges and attention deficit hyperactivity disorder (ADHD) are more common in children with perinatal stroke (19-35%) than peers (5-7%). Resting state (RS) functional magnetic resonance imaging (fMRI) measures fluctuations in the blood-oxygen level dependent (BOLD) signal that may estimate network functional connectivity (FC). We evaluated relationships between FC in relevant frontal circuits, ADHD and executive function in children with perinatal stroke compared to typically developing controls (TDC). Participant recruitment was from a population-based research cohort (AIS N=32; PVI N=30; TDC N=59). MRI imaging included T1-weighted anatomical and resting state fMRI sequences. Subsequent seed-to-seed analyses quantified FC within frontoparietal (FPN), dorsal attention (DAN) and default mode networks (DMN). Parent questionnaires quantified executive function (Behavior Rating Inventory of Executive Function (BRIEF)) and ADHD symptoms (ADHD Rating Scale-5). Large group FC differences were observed within FPN, DAN and DMN networks where AIS had lower FC compared to both PVI and TDC. For stroke participants, higher FC within the DAN and FPN was associated with poorer cognitive function (BRIEF). By contrast, higher FC within the DMN was associated with better ADHD ratings. Differences within frontal functional networks appear to be related to poorer cognitive function such that increased FC between the lesioned and nonlesioned hemisphere is associated with symptoms of executive dysfunction and ADHD suggesting that developmental plasticity leads to complex network changes following early unilateral brain injury.

Dysregulation of Ki-67 Expression in T Cells of Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral abnormalities such as impairments in social function and deficits in communication. The etiology of autism is unknown in most cases, but many studies have pointed towards the immune system as a causative agent in autism. Specific studies implicated lymphocytes, natural killer (NK) cells, monocytes, cytokines, and specific transcription factors in the development of ASD. The protein Ki-67 is n expressed in the proliferating cells and is used as a tool in several disorders. Ki-67 plays a crucial role in many neurological diseases. However, Ki-67 role in ASD is not fully understood. In this study, we investigated the possible role of Ki-67 expression in autistic children. We compared Ki-67 production in CD3+, CD4+, CD8+, CXCR4+, CXCR7+, CD45R+, HLA-DR+, GATA3+, Helios+, and FOXP3+ peripheral blood mononuclear cells (PBMCs) in autistic children to typically developing (TD) controls using immunofluorescence staining. We also determined Ki-67 mRNA levels in PBMCs using RT–PCR. The results revealed that autistic children had significantly increased numbers of CD3+Ki-67+, CD4+Ki-67+, CD8+Ki-67+, CXCR4+Ki-67+, CXCR7+Ki-67+, CD45R+Ki-67+, HLA-DR+Ki-67+, CXCR4+GATA3+, GATA3+Ki-67+ cells and decreased Helios+Ki-67+ and FOXP3+Ki-67+ cells compared with TD controls. In addition, the autistic children showed upregulation of Ki-67 mRNA levels compared with TD controls. Further studies need to be carried out to assess the exact role of Ki-67 and its therapeutic potential in ASD.

Neuropsychological Subgroups of Emotion Processing in Youths With Conduct Disorder.

Background: At the group level, youths with conduct disorder (CD) show deficient emotion processing across various tasks compared to typically developing controls (TDC). But little is known about neuropsychological subgroups within the CD population, the clinical correlates of emotion processing deficits [for instance, with regard to the presence or absence of the DSM-5 Limited Prosocial Emotions (LPE) specifier], and associated risk factors.Methods: 542 children and adolescents with CD (317 girls) and 710 TDCs (479 girls), aged 9–18 years, were included from the FemNAT-CD multisite study. All participants completed three neuropsychological tasks assessing emotion recognition, emotion learning, and emotion regulation. We used a self-report measure of callous-unemotional traits to create a proxy for the LPE specifier.Results: Relative to TDCs, youths with CD as a group performed worse in all three emotion domains. But using clinically based cut-off scores, we found poor emotion recognition skills in only 23% of the participants with CD, followed by emotion regulation deficits in 18%, and emotion learning deficits in 13% of the CD group. Critically, the majority of youths with CD (~56%) did not demonstrate any meaningful neuropsychological deficit, and only a very small proportion showed pervasive deficits across all three domains (~1%). Further analyses indicate that established DSM-5 subtypes of CD are not tightly linked to neurocognitive deficits in one particular emotion domain over another (i.e., emotion recognition deficits in CD+LPE vs. emotion regulation deficits in CD–LPE).Conclusions: Findings from this large-scale data set suggest substantial neuropsychological diversity in emotion processing in the CD population and, consequently, only a subgroup of youths with CD are likely to benefit from additional behavioral interventions specifically targeting emotion processing mechanisms.

The integrated functions of the cardiac autonomic and vestibular/oculomotor systems in adolescents following severe traumatic brain injury and typically developing controls

ABSTRACT Introduction The cardiac autonomic control system (CACS) is frequently impaired post-traumatic brain injury (TBI). However, the prevalence of vestibular/oculomotor impairment is less studied. These two systems interact during position change and contribute to blood-pressure regulation through the vestibulo-sympathetic reflex. Aim: To assess the CACS, the vestibular/oculomotor systems and their integrative function in adolescents post-TBI compared to typically-developing (TD) adolescents. Methods: 19 adolescents in the subacute stage following a severe TBI (14–117 days post injury) and 19 age and sex matched TD controls were recruited. Heart Rate Variability (HRV) was assessed at rest and during a modified tilt-test. A quantified version of the Vestibular/Ocular-Motor Screening (VOMS) was also administered. Results: At rest, the TBI group had higher HR and lower HRV values (p < .001). All participants with TBI demonstrated impairments in the VOMS (median of positive tests: 5 [range 2–9]) compared to only 6 out of 19 in the TD participants (median 0 [0–2]) (z = −5.34; p < .001). In response to the modified tilt test, the HRV increased significantly in the lifting period and decreased significantly once in standing only in the TBI group (z = −2.85, p = .025). Conclusion: Adolescents post severe TBI demonstrated impairments in the CACS, positive tests on the VOMS and significantly greater changes in the modified tilt test as compared to TD. Clinical trial gov. number: NCT03215082

Anterior and posterior commissures in agenesis of the corpus callosum: Alternative pathways for attention processes?

Developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation resulting from disruption of corpus callosum formation, a structure that is crucial for the transfer and integration of information, including attention processes, across the brain. This study aimed to investigate previously proposed candidates for alternative inter-hemispheric pathways in AgCC by examining (1) white matter volume and microstructure of the anterior and posterior commissures in children with AgCC compared to typically developing controls (TDC), and (2) in children with AgCC, examine the associations of white matter volume and microstructure of the anterior and posterior commissures and any remaining corpus callosum with attention processes. Participants were 21 children with AgCC (13 complete, 8 partial) recruited from The Royal Children's Hospital, Melbourne, and 30 TDC aged 8–17 years. T1-and diffusion-weighted MR sequences were used to calculate volume and microstructural parameters. Neuropsychological testing assessed attention processes. We found the anterior commissure was significantly larger in volume in children with AgCC than TDC (p = .027), with reduced mean FA (p = .001) associated with increased mean RD (p < .001). In children with AgCC, we found microstructural properties of the anterior commissure associated with attentional processes, specifically, mean FA of the anterior commissure was associated with better divided attention (p = .03), and the association between alerting attention and mean AD and RD was found to be moderated by age (p = .027, p = .008) and the degree of corpus callosum agenesis (p = .025, p = .016). Furthermore, in partial AgCC, larger posterior commissure volume was associated with better orienting attention (p = .035). In conclusion, we provide evidence that the volume and microstructure of the anterior commissure are altered in children with AgCC, and this neuroplastic response might have an influence on attention processes.