Age-matched Neurotypical Controls Research Articles

Correction of Batch Effect in Gut Microbiota Profiling of ASD Cohorts from Different Geographical Origins.

To date, there have been numerous metataxonomic studies on gut microbiota (GM) profiling based on the analyses of data from public repositories. However, differences in study population and wet and dry pipelines have produced discordant results. Herein, we propose a biostatistical approach to remove these batch effects for the GM characterization in the case of autism spectrum disorders (ASDs). An original dataset of GM profiles from patients with ASD was ecologically characterized and compared with GM public digital profiles of age-matched neurotypical controls (NCs). Also, GM data from seven case-control studies on ASD were retrieved from the NCBI platform and exploited for analysis. Hence, on each dataset, conditional quantile regression (CQR) was performed to reduce the batch effects originating from both technical and geographical confounders affecting the GM-related data. This method was further applied to the whole dataset matrix, obtained by merging all datasets. The ASD GM markers were identified by the random forest (RF) model. We observed a different GM profile in patients with ASD compared with NC subjects. Moreover, a significant reduction of technical- and geographical-dependent batch effects in all datasets was achieved. We identified Bacteroides_H, Faecalibacterium, Gemmiger_A_73129, Blautia_A_141781, Bifidobacterium_388775, and Phocaeicola_A_858004 as robust GM bacterial biomarkers of ASD. Finally, our validation approach provided evidence of the validity of the QCR method, showing high values of accuracy, specificity, sensitivity, and AUC-ROC. Herein, we proposed an updated biostatistical approach to reduce the technical and geographical batch effects that may negatively affect the description of bacterial composition in microbiota studies.

Differential Tractography: A Biomarker for Neuronal Function in Neurodegenerative Disease.

GM1 gangliosidosis is an ultra-rare inherited neurodegenerative lysosomal storage disorder caused by biallelic mutations in the GLB1 gene. GM1 is uniformly fatal and has no approved therapies, although clinical trials investigating gene therapy as a potential treatment for this condition are underway. Novel outcome measures or biomarkers demonstrating the longitudinal effects of GM1 and potential recovery due to therapeutic intervention are urgently needed to establish efficacy of potential therapeutics. One promising tool is differential tractography, a novel imaging modality utilizing serial diffusion weighted imaging (DWI) to quantify longitudinal changes in white matter microstructure. In this study, we present the novel use of differential tractography in quantifying the progression of GM1 alongside age-matched neurotypical controls. We analyzed 113 DWI scans from 16 GM1 patients and 32 age-matched neurotypical controls to investigate longitudinal changes in white matter pathology. GM1 patients showed white matter degradation evident by both the number and size of fiber tract loss. In contrast, neurotypical controls showed longitudinal white matter improvements as evident by both the number and size of fiber tract growth. We also corroborated these findings by documenting significant correlations between cognitive global impression (CGI) scores of clinical presentations and our differential tractography derived metrics in our GM1 cohort. Specifically, GM1 patients who lost more neuronal fiber tracts also had a worse clinical presentation. This result demonstrates the importance of differential tractography as an important biomarker for disease progression in GM1 patients with potential extension to other neurodegenerative diseases and therapeutic intervention.

‘Remote inhibition’ of motor cortex in Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS): A TMS based cortical excitability study

ObjectivesThe study compared real-time motor cortex excitability using transcranial magnetic stimulation (TMS)-derived parameters between children with epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and age-matched neurotypical controls. The EE-SWAS group received steroids as standard of care and were longitudinally followed for three months. Materials & MethodsChildren aged 5–12 years with immunotherapy-naive EE-SWAS (spike-wave-index≥50 %) and neurotypical controls were enrolled. Cognitive and behavioral assessments were performed using valid psychometric tools. Real-time motor cortex excitability was assessed by measuring resting motor threshold (RMT), short intra-cortical inhibition (SICI) and long intra-cortical inhibition (LICI) in both groups. In EE-SWAS group, a follow up evaluation with TMS at 4- and 12-week intervals, EEG, and neurobehavioral assessments at 12-weeks were performed to assess the effect of steroids on cortical excitability and to determine electroclinical outcome. ResultsForty-eight children with suspected EE-SWAS and 26 neurotypical controls were screened; 20 were enrolled in each group. Children with EE-SWAS (mean age: 8.05 ± 1.76 years) had cognitive and behavioral problems (20/20), and ongoing seizures (12/20). At baseline, the dominant motor cortex was significantly inhibited in the EE-SWAS group compared to neurotypical children{RMT(%)[86.3 ± 6.96 vs 58.05 ± 4.71(p < 0.0001)]; LICI(%)[55.05 ± 4.39 vs 73.9 ± 3.75(p < 0.0001)]; SICI(%)[39.2 ± 4.36 vs 55.45 ± 4.78(p < 0.0001)]}. Reversal of motor cortex inhibition was sequentially observed in EE-SWAS group at 4- and 12-week follow-ups{(RMT[4, 12 weeks]: 71.45 ± 9.83, 63.45 ± 8.48); (LICI[4, 12 weeks]: 66.00 ± 6.26, 74.50 ± 5.36); (SICI[4, 12 weeks]: 49.35 ± 6.24, 56.05 ± 5.57)}[repeated-measures ANOVA: p < 0.0001]. ConclusionMotor cortex is remotely inhibited in EE-SWAS, which may contribute to neurobehavioral impairment. Steroids can disinhibit/reverse the epilepsy-induced motor cortex inhibition leading to improvement in neurobehavior.

Impaired inhibitory control when processing real but not cartoon emotional faces in autistic children: Evidence from an event-related potential study.

Impaired socioemotional functioning characterizes autistic children, but does weak inhibition control underlie their socioemotional difficulty? This study addressed this question by examining whether and, if so, how inhibition control is affected by face realism and emotional valence in school-age autistic and neurotypical children. Fifty-two autistic and 52 age-matched neurotypical controls aged 10-12 years completed real and cartoon emotional face Go/Nogo tasks while event-related potentials (ERPs) were recorded. The analyses of inhibition-emotion components (i.e., N2, P3, and LPP) and a face-specific N170 revealed that autistic children elicited greater N2 while inhibiting Nogo trials and greater P3/LPP and late LPP for real but not cartoon emotional faces. Moreover, autistic children exhibited a reduced N170 to real face emotions only. Furthermore, correlation results showed that better behavioral inhibition and emotion recognition in autistic children were associated with a reduced N170. These findings suggest that neural mechanisms of inhibitory control in autistic children are less efficient and more disrupted during real face processing, which may affect their age-appropriate socio-emotional development.

Goal conceptualization has distinct effects on spatial and temporal bimanual coordination after left- and right- hemisphere stroke

Perception of task goal influences motor performance and coordination. In bimanual actions, it is unclear how one's perception of task goals influences bimanual coordination and performance in individuals with unilateral stroke. We characterized inter-limb coordination differences in individuals with chronic right- and left-hemisphere damaged (RCVA: n = 24, LCVA: n = 24) stroke and age-matched neurotypical controls (n = 24) as they completed bimanual reaching tasks under distinct goal conditions. In the dual-goal condition, participants reached to move two virtual bricks (cursors) assigned to each hand toward independent targets. In the common-goal condition, they moved a central common virtual brick representing both hands to a single, central target. Spatial and temporal coordination (cross-correlation coefficients of hand velocity and their time-lag), the redundant axis deviations (the hand deviations in the axis orthogonal to the axis along the cursor-target direction), and the contribution ratio of the paretic hand were measured. Compared to the dual-goal condition, reaching actions to the common-goal demonstrated better spatial bimanual coordination in all three participant groups. Temporal coordination was better during common-goal than dual-goal actions only for the LCVA group. Additionally, and novel to this field, sex, as a biological variable, differently influenced movement time and redundant axis deviation in participants with stroke under the common-goal condition. Specifically, female stroke survivors showed larger movements in the redundant axes and, consequently, longer movement times, which was more prominent in the LCVA group. Our results indicate that perception of task goals influences bimanual coordination, with common goal improving spatial coordination in neurotypical individuals and individuals with unilateral stroke and providing additional advantage for temporal coordination in those with LCVA. Sex influences bimanual performance in stroke survivors and needs to be considered in future investigations.

Similar Gap-Overlap Profiles in Children with Fragile X Syndrome and IQ-Matched Autism.

Fragile X syndrome (FXS) is a single-gene disorder characterized by moderate to severe cognitive impairment and a high association with autism spectrum disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). Atypical visual attention is a feature of FXS, ASD, and ADHD. Thus, studying early attentional patterns in young children with FXS can offer insight into early emerging neurocognitive processes underlying challenges and contribute to our understanding of common and unique features of ASD and ADHD in FXS. The present study examined visual attention indexed by the gap-overlap paradigm in children with FXS (n = 39) compared to children with ASD matched on intellectual ability and age (n = 40) and age-matched neurotypical controls (n = 34). The relationship between gap-overlap performance and intellectual ability, ASD, and ADHD across groups was characterized. Saccadic reaction times (RT) were collected across baseline, gap, and overlap conditions. Results indicate no group differences in RT for any conditions. However, RT of the ASD and NT groups became slower throughout the experiment whereas RT of the FXS group did not change, suggesting difficulties in habituation for the FXS group. There was no relationship between RT and intellectual ability, ADHD, or ASD symptoms in the FXS and ASD groups. In the NT group, slower RT was related to elevated ADHD symptoms only. Taken together, findings suggest that the social attention differences documented in FXS and ASD may be due to other cognitive factors, such as reward or motivation, rather than oculomotor control of visual attention.

Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis

The neurophysiological basis of autism spectrum disorder (ASD) is still uncertain. Nevertheless, studies support the hypotheses that oxidative stress, neuroinflammation, immune dysregulation, and metabolic stress are contributors. In this study, the serum levels of 3-nitrotyrosine (3-NT), hypoxia-inducible factor 1 α (HIF-1 α), heat shock protein 70 (HSP-70), interleukin-17A (IL-17A), IL-35, vitamin D3 (VITD), glucose transporter-1 (GUT1), and AMP-activated protein kinase (AMPK) were estimated in Saudi ASD children versus age-matched neurotypical controls, aiming to investigate whether these parameters have potential roles in the pathophysiologic mechanisms of ASD and hoping to find a reliable marker for early ASD diagnosis. This study included 25 ASD children and 25 typically developing children (3–11 years old). The diagnosis of ASD cases was made based on the Autism Diagnostic Observation Schedule (ADOS) and the Statistical Manual of Mental Disorders (DSM-5). ASD subjects were commonly male and revealed an intelligence quotient (IQ) < 70.The results detected that ASD children have remarkable greater serum levels of nitrosative stress (3-NT), hypoxia (HIF-1 α), inflammatory (HSP-70, IL-17A, and AMPK) biomarkers and lower serum levels of anti-inflammatory (IL-35 and VITD) and metabolic stress (GUT-1) biomarkers versus age-matched controls (P ≤ 0.0001). Pearson's correlation study revealed that 3-NT was positively associated with HIF-1 α and HSP-70. HIF-1 α was also positively correlated with HSP-70. AMPK was positively associated with GUT-1, however, IL-17A was negatively correlated with IL-35 and VITD.Limitation:No specific therapeuticdrugs were administered in this study, and further studies are required to confirm the role of the selected biomarkers in ASD managements. ConclusionChanges in concentrations of different biomarkers indicate that they are involved in oxidative stress, metabolic stress, immune dysregulation and ASD pathogenesis. Hence, these parameters can prove to be promising biomarkers as well as therapeutic targets for the timely diagnosis and treatment of ASD patients.

Resting-State EEG Microstates and Power Spectrum in Borderline Personality Disorder: A High-Density EEG Study

Borderline personality disorder (BPD) is a debilitating psychiatric condition characterized by emotional dysregulation, unstable sense of self, and impulsive, potentially self-harming behavior. In order to provide new neurophysiological insights on BPD, we complemented resting-state EEG frequency spectrum analysis with EEG microstates (MS) analysis to capture the spatiotemporal dynamics of large-scale neural networks. High-density EEG was recorded at rest in 16 BPD patients and 16 age-matched neurotypical controls. The relative power spectrum and broadband MS spatiotemporal parameters were compared between groups and their inter-correlations were examined. Compared to controls, BPD patients showed similar global spectral power, but exploratory univariate analyses on single channels indicated reduced relative alpha power and enhanced relative delta power at parietal electrodes. In terms of EEG MS, BPD patients displayed similar MS topographies as controls, indicating comparable neural generators. However, the MS temporal dynamics were significantly altered in BPD patients, who demonstrated opposite prevalence of MS C (lower than controls) and MS E (higher than controls). Interestingly, MS C prevalence correlated positively with global alpha power and negatively with global delta power, while MS E did not correlate with any measures of spectral power. Taken together, these observations suggest that BPD patients exhibit a state of cortical hyperactivation, represented by decreased posterior alpha power, together with an elevated presence of MS E, consistent with symptoms of elevated arousal and/or vigilance. This is the first study to investigate resting-state MS patterns in BPD, with findings of elevated MS E and the suggestion of reduced posterior alpha power indicating a disorder-specific neurophysiological signature previously unreported in a psychiatric population.

Utilizing the ISway to Identify and Compare Balance Domain Deficits in People with Multiple Sclerosis

Background and Purpose Balance impairments are a common symptom in people with Multiple Sclerosis (PwMS). The instrumented sway (ISway) is a reliable clinical balance assessment; however, this approach yields a vast range of outcomes that may hinder interpretation and delivery of evidence-based care. Identifying balance domains that are both altered in PwMS and clinically relevant would help isolate treatment targets. Therefore, we sought to develop a multiple sclerosis (MS)-specific model of balance and examine differences between 1) PwMS and neurotypical controls and 2) PwMS with (MS-F) and without a fall history (MS-NF). Methods 118 people with relapsing-remitting MS (MS-F = 39; MS-NF = 79) and 46 age-matched neurotypical controls completed the ISway balance assessment. 22 sway measures obtained from the ISway were entered into an exploratory factor analysis (EFA) to identify underlying balance domains. The model-derived balance domains were compared between 1) PwMS and age-matched, neurotypical controls and 2) MS-F and MS-NF. Results 3 distinct balance domains were identified: 1) sway amplitude and velocity, 2) sway frequency and jerk mediolateral (ML), and 3) sway frequency and jerk anteroposterior (AP), explaining 81.66% of balance variance. PwMS exhibited worse performance (i.e., greater amplitude and velocity of sway) in the sway velocity and amplitude domain compared to age-matched neurotypical controls (p = .003). MS-F exhibited worse performance in the sway velocity and amplitude domain compared to MS-NF (p = 0.046). The AP and ML sway frequency and jerk domains were not different between PwMS and neurotypical controls nor between MS-F and MS-NF. Discussion PwMS exhibited deficits within the sway amplitude and velocity domain compared to neurotypical controls, with a similar effect observed between MS-F and MS-NF. Recognizing balance domains altered in PwMS and related to falls may be useful for efficient and strategic balance assessment and rehabilitation. Balance impairments are a common symptom in people with Multiple Sclerosis (PwMS). The instrumented sway (ISway) is a reliable clinical balance assessment; however, this approach yields a vast range of outcomes that may hinder interpretation and delivery of evidence-based care. Identifying balance domains that are both altered in PwMS and clinically relevant would help isolate treatment targets. Therefore, we sought to develop a multiple sclerosis (MS)-specific model of balance and examine differences between 1) PwMS and neurotypical controls and 2) PwMS with (MS-F) and without a fall history (MS-NF). 118 people with relapsing-remitting MS (MS-F = 39; MS-NF = 79) and 46 age-matched neurotypical controls completed the ISway balance assessment. 22 sway measures obtained from the ISway were entered into an exploratory factor analysis (EFA) to identify underlying balance domains. The model-derived balance domains were compared between 1) PwMS and age-matched, neurotypical controls and 2) MS-F and MS-NF. 3 distinct balance domains were identified: 1) sway amplitude and velocity, 2) sway frequency and jerk mediolateral (ML), and 3) sway frequency and jerk anteroposterior (AP), explaining 81.66% of balance variance. PwMS exhibited worse performance (i.e., greater amplitude and velocity of sway) in the sway velocity and amplitude domain compared to age-matched neurotypical controls (p = .003). MS-F exhibited worse performance in the sway velocity and amplitude domain compared to MS-NF (p = 0.046). The AP and ML sway frequency and jerk domains were not different between PwMS and neurotypical controls nor between MS-F and MS-NF. PwMS exhibited deficits within the sway amplitude and velocity domain compared to neurotypical controls, with a similar effect observed between MS-F and MS-NF. Recognizing balance domains altered in PwMS and related to falls may be useful for efficient and strategic balance assessment and rehabilitation.

Using the Instrumented Sway System (ISway) to Identify and Compare Balance Domain Deficits in People With Multiple Sclerosis

ObjectiveTo develop a multiple sclerosis (MS)-specific model of balance and examine differences between (1) MS and neurotypical controls and (2) people with MS (PwMS) with (MS-F) and without a fall history (MS-NF). Design and SettingA cross-sectional study was conducted at the Gait and Balance Laboratory at the University of Kansas Medical Center. Balance was measured from the instrumented sway system (ISway) assessment. ParticipantsIn total, 118 people with relapsing-remitting MS (MS-F=39; MS-NF=79) and 46 age-matched neurotypical controls. InterventionNot applicable. Outcome MeasuresA total of 22 sway measures obtained from the ISway were entered into an exploratory factor analysis to identify underlying balance domains. The model-derived balance domains were compared between (1) PwMS and age-matched, neurotypical controls and (2) MS-F and MS-NF. ResultsThree distinct balance domains were identified: (1) sway amplitude and velocity, (2) sway frequency and jerk mediolateral, and (3) sway frequency and jerk anteroposterior, explaining 81.66% of balance variance. PwMS exhibited worse performance (ie, greater amplitude and velocity of sway) in the sway velocity and amplitude domain compared to age-matched neurotypical controls (P=.003). MS-F also exhibited worse performance in the sway velocity and amplitude domain compared to MS-NF (P=.046). The anteroposterior and mediolateral sway frequency and jerk domains were not different between PwMS and neurotypical controls nor between MS-F and MS-NF. ConclusionsThis study identified a 3-factor, MS-specific balance model, demonstrating that PwMS, particularly those with a fall history, exhibit disproportionate impairments in sway amplitude and velocity. Identifying postural stability outcomes and domains that are altered in PwMS and clinically relevant (eg, related to falls) would help isolate potential treatment targets.

A Pilot Study of Ex Vivo Human Prefrontal RNA Transcriptomics in Parkinson's Disease.

Parkinson's disease (PD) can dramatically change cortical neurophysiology. The molecular basis for PD-related cortical changes is unclear because gene expression data are usually derived from postmortem tissue collected at the end of a complex disease and they profoundly change in the minutes after death. Here, we studied cortical changes in tissue from the prefrontal cortex of living PD patients undergoing deep-brain stimulation implantation surgery. We examined 780 genes using the NanoString nCounter platform and found that 40 genes were differentially expressed between PD (n = 12) and essential tremor (ET; n = 9) patients. One of these 40 genes, STAT1, correlated with intraoperative 4-Hz rhythms and intraoperative performance of an oddball reaction-time task. Using a pre-designed custom panel of 780 targets, we compared these intraoperative data with those from a separate cohort of fresh-frozen tissue from the same frontal region in postmortem human PD donors (n = 6) and age-matched neurotypical controls (n = 6). This cohort revealed 279 differentially expressed genes. Fifteen of the 40 intraoperative PD-specific genes overlapped with postmortem PD-specific genes, including CALB2 and FOXP2. Transcriptomic analyses identified pathway changes in PD that had not been previously observed in postmortem cases. These molecular signatures of cortical function and dysfunction may help us better understand cognitive and neuropsychiatric aspects of PD.

Visual processing in genetic conditions linked to autism: A behavioral study of binocular rivalry in individuals with 16p11.2 deletions and age-matched controls.

Close phenotypic characterization of individuals with genetic conditions linked to autism provides a promising approach to navigating the heterogeneity of autism spectrum conditions. The current study investigated sensory processing in individuals with a rare genetic event that is highly penetrant for autism, 16p11.2 deletions, using a well-characterized visual paradigm, binocular rivalry, which is thought to be a non-invasive index of excitatory/inhibitory balance in the visual cortex. We characterized rivalry dynamics in 45 adolescent and adult individuals (19 individuals with 16p11.2 deletions, 26 age-matched neurotypical controls). We found that binocular rivalry perceptual transition rates were significantly slower for individuals with 16p11.2 deletions, relative to controls. Importantly, these results could not be accounted for by differences in motor response latencies or perceptual decision criteria, which were matched between groups. Results should be interpreted with caution given the unmatched psychometric features between groups, such as IQ. Future studies should study visual processing in other genetic groups linked to autism beyond 16p to understand the specificity of these findings. These results highlight the importance of characterizing sensory functions in individuals with genetic alterations associated with autism.

Markers related to oxidative stress in peripheral blood in children with autism spectrum disorder

BackgroundOxidative stress in the brain contributes to neuronal damage in genetically susceptible children, which might be involved in the pathophysiology of autism spectrum disorder(ASD). However, clinical data were inconsistent. The goal of this study was to investigate whether oxidative stress markers (vitamin A and vitamin E concentrations and leukocyte mitochondrial DNA copy number and telomere length) in peripheral blood are related to ASD in Chinese children aged 6–9 years. MethodSixty seven individuals with ASD and 134 sex- and age-matched neurotypical controls participated. The relative mitochondrial DNA copy number (mtDNAcn) and telomere length of leukocytes in peripheral blood were measured using quantitative real-time polymerase chain reaction. The vitamin A and vitamin E concentrations in plasma were determined using reversed-phase high-performance liquid chromatography. ResultsASD group had a higher leukocyte mtDNAcn (1.36 ± 0.49 vs. 1.03 ± 0.24, p < 0.001) and vitamin E concentration (5.79 ± 1.70 ng/ml vs. 5.30 ± 0.96 ng/ml, p = 0.044) than the control group, but no significant differences in vitamin A concentration and leukocyte telomere length were detected between groups. Leukocyte mtDNAcn in the highest tertile increased the risk of ASD by 4.259 times (odds ratio:4.259, 95% confidence interval: 1.427–12.707, p = 0.009) compared with the lowest tertile after adjustment for confounders, and a significant dose–response relationship between mtDNAcn and ASD risk was observed (p-trend = 0.032). ConclusionsChildren with ASD had higher levels of leukocyte mtDNAcn.

Changes to the Gut Microbiome in Young Children Showing Early Behavioral Signs of Autism.

The human gut microbiome has increasingly been associated with autism spectrum disorder (ASD), which is a neurological developmental disorder, characterized by impairments to social interaction. The ability of the gut microbiota to signal across the gut-brain-microbiota axis with metabolites, including short-chain fatty acids, impacts brain health and has been identified to play a role in the gastrointestinal and developmental symptoms affecting autistic children. The fecal microbiome of older children with ASD has repeatedly shown particular shifts in the bacterial and fungal microbial community, which are significantly different from age-matched neurotypical controls, but it is still unclear whether these characteristic shifts are detectable before diagnosis. Early microbial colonization patterns can have long-lasting effects on human health, and pre-emptive intervention may be an important mediator to more severe autism. In this study, we characterized both the microbiome and short-chain fatty acid concentrations of fecal samples from young children between 21 and 40 months who were showing early behavioral signs of ASD. The fungal richness and acetic acid concentrations were observed to be higher with increasing autism severity, and the abundance of several bacterial taxa also changed due to the severity of ASD. Bacterial diversity and SCFA concentrations were also associated with stool form, and some bacterial families were found with differential abundance according to stool firmness. An exploratory analysis of the microbiome associated with pre-emptive treatment also showed significant differences at multiple taxonomic levels. These differences may impact the microbial signaling across the gut-brain-microbiota axis and the neurological development of the children.

Categorical Perception of Pitch Contours and Voice Onset Time in Mandarin-Speaking Adolescents With Autism Spectrum Disorders.

Purpose Previous studies have shown enhanced pitch and impaired time perception in individuals with autism spectrum disorders (ASD). However, it remains unclear whether such deviated patterns of auditory processing depending on acoustic dimensions would transfer to the higher level linguistic pitch and time processing. In this study, we compared the categorical perception (CP) of lexical tones and voice onset time (VOT) in Mandarin Chinese, which utilize pitch and time changes, respectively, to convey phonemic contrasts. Method The data were collected from 22 Mandarin-speaking adolescents with ASD and 20 age-matched neurotypical controls. In addition to the identification and discrimination tasks to test CP performance, all the participants were evaluated with their language ability and phonological working memory. Linear mixed-effects models were constructed to evaluate the identification and discrimination scores across different groups and conditions. Results The basic CP pattern of cross-boundary benefit when perceiving both native lexical tones and VOT was largely preserved in high-functioning adolescents with ASD. The degree of CP of lexical tones in ASD was similar to that in typical controls, whereas the degree of CP of VOT in ASD was greatly reduced. Furthermore, the degree of CP of lexical tones correlated with language ability and digit span in ASD participants. Conclusions These findings suggest that the unbalanced acoustic processing capacities for pitch and time can be generalized to the higher level linguistic processing in ASD. Furthermore, the higher degree of CP of lexical tones correlated with better language ability in Mandarin-speaking individuals with ASD.

Rational Adaptation in Using Conceptual Versus Lexical Information in Adults With Aphasia.

The information theoretic principle of rational adaptation predicts that individuals with aphasia adapt to their language impairments by relying more heavily on comparatively unimpaired non-linguistic knowledge to communicate. This prediction was examined by assessing the extent to which adults with chronic aphasia due to left-hemisphere stroke rely more on conceptual rather than lexical information during verb retrieval, as compared to age-matched neurotypical controls. A primed verb naming task examined the degree of facilitation each participant group received from either conceptual event-related or lexical collocate cues, compared to unrelated baseline cues. The results provide evidence that adults with aphasia received amplified facilitation from conceptual cues compared to controls, whereas healthy controls received greater facilitation from lexical cues. This indicates that adaptation to alternative and relatively unimpaired information may facilitate successful word retrieval in aphasia. Implications for models of rational adaptation and clinical neurorehabilitation are discussed.

Are Obese Patients with Autism Spectrum Disorder More Likely to Be Selenium Deficient? Research Findings on Pre- and Post-Pubertal Children.

Selenium is involved in many metabolic pathways that are critical for life. Information concerning the metabolic effects of selenium in autism spectrum disorder (ASD) and obesity is still conflicting and incomplete. The pre- and post-pubertal selenium profiles of patients with ASD and obesity have not yet been investigated. The goal of the study was to examine selenium content before and after puberty in euthyroid children diagnosed with ASD, compared to age-matched neurotypical controls, with respect to overweight or obesity as a co-existing pathology. Serum, toenail, and 24h urine selenium levels were determined by inductively coupled plasma mass spectrometry in 287 prepubertal children (mean age 8.09 years), divided into groups: ASD with overweight/obesity (ASD+/Ob+); ASD without overweight/obesity (ASD+/Ob−); non-ASD with overweight/obesity (ASD−/Ob+); and non-ASD without overweight/obesity (ASD−/Ob−). The assessment was repeated in 258 of the children after puberty (mean age 14.26 years).The lowest serum (p < 0.001), urine (p < 0.001) and toenail (p < 0.001) selenium levels before and after puberty were observed in ASD+/Ob+ patients, and the highest in ASD−/Ob−. There were no differences in serum/toenail selenium levels between ASD+/Ob− and ASD−/Ob+ groups. The presence of ASD was associatedwith lower serum (p < 0.001) and toenail (p < 0.001) selenium in BMI-matched groups. In neurotypical patients, post-pubertal serum selenium levels were lower (p < 0.001) than pre-pubertal levels. In the multiple linear regression analyses, selenium levels showed inverse relationships with BMI (p < 0.001) and male gender (p < 0.001), irrespective of the sample type. The serum (p = 0.002) and toenail (p < 0.001) selenium levels were inversely associated with the presence of ASD. ASD, obesity/overweight, and male gender have independent impacts on selenium levels in children. Puberty may affect selenium content in neurotypical children of both genders, but not in ASD patients.

Quantitative EEG Analysis in Angelman Syndrome: Candidate Method for Assessing Therapeutics.

The goal of these studies was to use quantitative (q)EEG techniques on data from children with Angelman syndrome (AS) using spectral power analysis, and to evaluate this as a potential biomarker and quantitative method to evaluate therapeutics. Although characteristic patterns are evident in visual inspection, using qEEG techniques has the potential to provide quantitative evidence of treatment efficacy. We first assessed spectral power from baseline EEG recordings collected from children with AS compared to age-matched neurotypical controls, which corroborated the previously reported finding of increased total power driven by elevated delta power in children with AS. We then retrospectively analyzed data collected during a clinical trial evaluating the safety and tolerability of minocycline (3 mg/kg/d) to compare pretreatment recordings from children with AS (4-12 years of age) to EEG activity at the end of treatment and following washout for EEG spectral power and epileptiform events. At baseline and during minocycline treatment, the AS subjects demonstrated increased delta power; however, following washout from minocycline treatment the AS subjects had significantly reduced EEG spectral power and epileptiform activity. Our findings support the use of qEEG analysis in evaluating AS and suggest that this technique may be useful to evaluate therapeutic efficacy in AS. Normalizing EEG power in AS therefore may become an important metric in screening therapeutics to gauge overall efficacy. As therapeutics transition from preclinical to clinical studies, it is vital to establish outcome measures that can quantitatively evaluate putative treatments for AS and neurological disorders with distinctive EEG patterns.

M76. ATYPICAL RESPONSE INHIBITION IN 22Q11.2DS: DIMINISHED ERROR REGISTRATION AND AWARENESS

Background22q11.2 deletion syndrome (22q11.2DS; also known as DiGeorge syndrome or velo-cardio-facial syndrome) is characterized by increased vulnerability for neuropsychiatric symptoms, with approximately 30% of the individuals with the deletion developing schizophrenia. Clinically, deficits in executive function have been noted in this population, but the underlying neural processes are not well understood.MethodsUsing high-density electrophysiology (EEG), we investigated the neural dynamics of inhibition of a prepotent response (a critical component of executive function) in individuals with 22q11.2DS with and without psychotic symptoms. Twenty-seven individuals with 22q11.2DS (14–35 years old, 14 with at least one psychotic symptom) and 27 age-matched neurotypical controls participated in a go/no-go task while EEG was recorded. Analyses were focused on the P3 go/no-go response and error-related positivity (Pe).ResultsBehaviorally, individuals with 22q11.2DS were slower and unable to inhibit prepotent responses as the controls, with significantly more false alarms. Atypical inhibitory processing was confirmed by significantly reduced P3 no-go responses in the 22q11.2DS group. Such reductions were particularly marked in those with psychotic symptomatology. Pe was likewise significantly decreased (regardless of the presence of psychotic symptoms), suggesting impaired ability to register errors (i.e., false alarms) in 22q11.2DS. Both Pe and P3 correlated with clinical measures of inhibition (DKEFS and CPT).DiscussionTo our knowledge, this is the first study looking at electrophysiological measures of response inhibition in 22q11.2DS. P3 and Pe reductions, which have also been shown in schizophrenia, suggest diminished error registration and awareness in 22q11.2DS and, possibly, a consequent difficulty in adjusting response strategies.

Atypical response inhibition and error processing in 22q11.2 Deletion Syndrome and schizophrenia: Towards neuromarkers of disease progression and risk

22q11.2 deletion syndrome (also known as DiGeorge syndrome or velo-cardio-facial syndrome) is characterized by increased vulnerability to neuropsychiatric symptoms, with approximately 30% of individuals with the deletion going on to develop schizophrenia. Clinically, deficits in executive function have been noted in this population, but the underlying neural processes are not well understood. Using a Go/No-Go response inhibition task in conjunction with high-density electrophysiological recordings (EEG), we sought to investigate the behavioral and neural dynamics of inhibition of a prepotent response (a critical component of executive function) in individuals with 22q11.2DS with and without psychotic symptoms, when compared to individuals with idiopathic schizophrenia and age-matched neurotypical controls. Twenty-eight participants diagnosed with 22q11.2DS (14–35 years old; 14 with at least one psychotic symptom), 15 individuals diagnosed with schizophrenia (18–63 years old) and two neurotypical control groups (one age-matched to the 22q11.2DS sample, the other age-matched to the schizophrenia sample) participated in this study. Analyses focused on the N2 and P3 no-go responses and error-related negativity (Ne) and positivity (Pe). Atypical inhibitory processing was shown behaviorally and by significantly reduced P3, Ne, and Pe responses in 22q11.2DS and schizophrenia. Interestingly, whereas P3 was only reduced in the presence of psychotic symptoms, Ne and Pe were equally reduced in schizophrenia and 22q11.2DS, regardless of the presence of symptoms. We argue that while P3 may be a marker of disease severity, Ne and Pe might be candidate markers of risk.