Core Diagnostic Features Research Articles

Attenuated responses to attention-modulating drugs in the neuroligin-3R451C mouse model of autism.

Attention deficits are frequently reported within the clinical autism population. Despite not being a core diagnostic feature, some aetiological theories place atypical attention at the centre of autism development. Drugs used to treat attention dysfunction are therefore increasingly prescribed to autistic patients, though currently off-label with uncertain efficacy. We utilised a rodent-translated touchscreen test of sustained attention in mice carrying an autism-associated R451C mutation in the neuroligin-3 gene (Nlgn3R451C). In doing so, we replicated their cautious but accurate response profile and probed it using two widely prescribed attention-modulating drugs: methylphenidate (MPH) and atomoxetine (ATO). In wild-type mice, acute administration of MPH (3 mg/kg) promoted impulsive responding at the expense of accuracy, while ATO (3 mg/kg) broadly reduced impulsive responding. These drug effects were absent in Nlgn3R451C mice, other than a small reduction in blank touches to the screen following ATO administration. The absence of drug effects in Nlgn3R451C mice likely arises from their altered behavioural baseline and underlying neurobiology, highlighting caveats to the use of classic attention-modulating drugs across disorders and autism subsets. It further suggests that altered dopaminergic and/or norepinephrinergic systems may drive behavioural differences in the Nlgn3R451C mouse model of autism, supporting further targeted investigation.

Applying the Consensus Criteria for Traumatic Encephalopathy Syndrome Retrospectively to Case Studies of Boxers from the 20th Century.

There are no validated diagnostic criteria for traumatic encephalopathy syndrome (TES). During the early and middle 20th century, TES was described as a clinical condition that was experienced by some high-exposure boxers-and it was believed to reflect chronic traumatic brain injury. Consensus criteria for the diagnosis of TES were published in 2021. We applied the consensus criteria for TES retrospectively to cases of chronic brain damage in boxers described in articles published in the 20th century that were obtained from narrative and systematic reviews. The sample included 157 boxers identified in 21 articles published between 1929 and 1999. Two authors reviewed each case description and coded the criteria for TES. For the core clinical features, cognitive impairment was noted in 63.1%, and in 28.7% of cases the person's cognitive functioning appeared to be broadly normal. Neurobehavioral dysregulation was present in 25.5%. One third (34.4%) were identified as progressive, 30.6% were not progressive, and the course could not be clearly determined in 35.0%. In total, 29.9% met the TES consensus criteria, 28.0% did not, and 42.0% had insufficient information to make a diagnostic determination. TES, in the 20th century, was described as a neurological condition, not a psychiatric disorder-and this supports the decision of the 2021 consensus group to remove primary and secondary psychiatric diagnoses from being a core diagnostic feature. Future research is needed to determine whether, or the extent to which, cognitive impairment or neurobehavioral dysregulation described as characterizing TES are associated with chronic traumatic encephalopathy neuropathological change.

A Delphi consensus on clinical features, diagnosis and treatment of major depressive disorder patients with anhedonia amongst psychiatrists in the Asia-Pacific.

Anhedonia, a core diagnostic feature for major depressive disorder (MDD), is defined as the loss of pleasure and interest in daily activities. Its prevalence in MDD patients vary from 35 to 70%. Anhedonia in MDD negatively impacts functioning and is associated with treatment resistance and poorer prognosis for various clinical outcomes. Owing to its complexity, there remains considerable heterogeneity in the conceptualization, diagnosis and clinical management of anhedonia in MDD. This modified Delphi panel was conducted to elicit expert opinion and establish consensus on concepts relating to clinical features, diagnosis and treatment of MDD with anhedonia (MDDwA) amongst psychiatrists in the Asia-Pacific region. Seven themes were covered. A three-stage process was adopted for consensus generation (two online survey rounds, followed by a moderated consensus meeting). Statements were developed based on a literature review and input from a steering committee of six regional experts. The panel included 12 psychiatrists practicing in Australia, China, Hong Kong, Japan, South Korea and Taiwan with ≥5 years of specialist clinical experience, including assessment or management of patients with MDDwA. Overall, consensus was achieved (median ≥8) on 89/103 statements (86%). About half of the statements (55/103, 53%) achieved consensus in Round 1, and 29/36 modified statements achieved consensus in Round 2. At the moderated consensus meeting, five modified statements were discussed by the steering committee and consensus was achieved on all statements (5/5). The findings highlighted a lack of clear and practical methods in clinical practice for assessing anhedonia in MDD patients and limited physician awareness of anhedonia in Asia-Pacific. Insights from this Delphi consensus provide a reference point for psychiatrists in Asia-Pacific to optimize their strategies for personalized diagnosis and management of patients with MDDwA. Identification of distinct and clinically relevant subtypes in MDD may be valuable for guiding personalized diagnosis and management approaches, including type-specific therapies.

Identifying parkinsonism in mild cognitive impairment

IntroductionClinical parkinsonism is a core diagnostic feature for mild cognitive impairment with Lewy bodies (MCI-LB) but can be challenging to identify. A five-item scale derived from the Unified Parkinson's Disease Rating Scale (UPDRS) has been recommended for the assessment of parkinsonism in dementia. This study aimed to determine whether the five-item scale is effective to identify parkinsonism in MCI. MethodsParticipants with MCI from two cohorts (n = 146) had a physical examination including the UPDRS and [123I]-FP-CIT SPECT striatal dopaminergic imaging. Participants were classified as having clinical parkinsonism (P+) or no parkinsonism (P-), and with abnormal striatal dopaminergic imaging (D+) or normal imaging (D-).The five-item scale was the sum of UPDRS tremor at rest, bradykinesia, action tremor, facial expression, and rigidity scores. The ability of the scale to differentiate P+D+ and P-D- participants was examined. ResultsThe five-item scale had an AUROC of 0.92 in Cohort 1, but the 7/8 cut-off defined for dementia had low sensitivity to identify P+D+ participants (sensitivity 25%, specificity 100%). Optimal sensitivity and specificity was obtained at a 3/4 cut-off (sensitivity 83%, specificity 88%).In Cohort 2, the five-item scale had an AUROC of 0.97, and the 3/4 cut-off derived from Cohort 1 showed sensitivity of 100% and a specificity of 82% to differentiate P+D+ from P-D- participants. The five-item scale was not effective in differentiating D+ from D- participants. ConclusionsThe five-item scale is effective to identify parkinsonism in MCI, but a lower threshold must be used in MCI compared with dementia.

Opioids and restless legs syndrome: a double-edged sword.

Opioids and restless legs syndrome: a double-edged sword.

Differentiated processing of emotional cues in adolescents and young adults with ICD-11 PTSD and complex PTSD after child abuse.

The recent update of the International Classification of Diseases 11th revision (ICD-11) introduced the diagnosis of complex posttraumatic stress disorder (CPTSD) as a distinct entity from posttraumatic stress disorder (PTSD). Because psychophysiological alterations are a core diagnostic feature of PTSD and CPTSD, the aim of the current study was to examine potential distinctive patterns in cortical and cardiac responses to emotional words in adolescent and young adult patients with PTSD and CPTSD. Event-related potentials and heart rate responses were studied in 81 adolescent and young adult participants, of which 17 individuals were diagnosed with ICD-11 PTSD and 32 individuals with CPTSD, each after childhood sexual and/or physical abuse. Thirty-two individuals served as healthy controls. The paradigm consisted of a passive reading task with neutral, positive, physically threatening, and socially threatening words. Differentiated early processing of emotional words was indicated by differences on P1 and left EPN components. Additionally, PTSD and CPTSD patients presented with specific patterns of heart rate responses to emotional words. In CPTSD patients, heart rate reactions to emotional words were more variable than in PTSD patients. These findings provide early evidence of differentiated cortical and cardiac response patterns in adolescent and young adult patients with CPTSD and PTSD, supporting a nosological distinction between PTSD and complex PTSD. However, due to small and unequal sample sizes, findings presented in the current study are preliminary and require future research.

Validating the repetitive behavior scale-revised for children in China aged 9 to 16 with autism spectrum disorder

Restricted and repetitive behavior (RRB) is one of the two core diagnostic features used to determine the severity of autism spectrum disorder (ASD). The Repetitive Behavior Scale‑Revised (RBS-R) is widely used to measure the presence and severity of a variety of RRBs in individuals with ASD. Previous studies have implemented a factor analysis framework to examine the RBS-R, while there’re still inconsistencies in the use of the measure. This study analyzed the validity and reliability of the RBS-R using data from 315 Chinese children aged 9–16 with ASD. The results showed that the original tested items were adaptable to the Chinese cultural environment when treating such disorders. A confirmatory factor analysis indicated that a 6-factor model was most suitable for evaluating RRB in this context. Consistent with previous studies, the 6-factor model was preferred because of its fit statistics in evaluating RRBs using data from Chinese children with ASD aged 9–16. It’s necessary to implement the same structure (e.g. 6-factor model) of the RBS-R to enable efficient comparisons of results across studies. Validating the RBS-R cross different contexts and using longitudinal data are helpful to advance our knowledge of RRB.

Altered temporal connectivity and reduced meta-state dynamism in adolescents born very preterm.

Adolescents born very preterm have an increased risk for anxiety, social difficulties and inattentiveness, i.e. the 'preterm behavioural phenotype'. The extreme end of these traits comprises the core diagnostic features of attention and hyperactivity disorders and autism spectrum disorder, which have been reported to show aberrant dynamic resting-state functional network connectivity. This study aimed to compare this dynamism between adolescents born very preterm and controls. A resting-state functional magnetic resonance imaging was performed on 24 adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) and 32 controls born full term (≥37 weeks of gestation) at 13 years of age. Group-wise comparisons of dynamic connectivity between the resting-state networks were performed using both hard clustering and meta-state analysis of functional network connectivity. The very preterm group yielded a higher fraction of time spent in the least active connectivity state in hard clustering state functional network connectivity, even though no group differences in pairwise connectivity patterns were discovered. The meta-state analysis showed a decreased fluidity and dynamic range in the very preterm group compared with controls. Our results suggest that the 13-year-old adolescents born very preterm differ from controls in the temporal characteristics of functional connectivity. The findings may reflect the long-lasting effects of prematurity and the clinically acknowledged 'preterm behavioural phenotype'.

Characterizing restricted and unusual interests in autistic youth.

A broad range of interests characterized by unusual content and/or intensity, labeled as circumscribed interests (CI), are a core diagnostic feature of autism. Recent evidence suggests that a distinction can be drawn between interests that, although characterized by unusually high intensity and/or inflexibility, are otherwise common in terms of their content (e.g., an interest in movies or animals), labeled as restricted interests (RI), and interests that are generally not salient outside of autism (e.g., an interest in traffic lights or categorization), labeled as unusual interests (UI). The current study aimed to further characterize RI and UI by exploring their association with age, sex, IQ, and social motivation, as well as to examine differences in the adaptive benefits and negative impacts of these two subdomains. Parents of 1892 autistic children and adolescents (Mage =10.82, SDage =4.14; 420 females) completed an online survey including the Dimensional Assessment of Restricted and Repetitive Behaviors and the Social Communication Questionnaire. Both RI and UI were found to be highly frequent. Sex-based differences were observed in the content, but not intensity, of CI such that females were more likely to show interests with a social component. Finally, RI and UI showed distinct patterns of association with age, sex, IQ, and social motivation, as well as metrics of adaptive benefits and negative impacts. Findings afford a more nuanced understanding of sex-based differences in CI and, crucially, provide preliminary evidence that RI and UI represent distinct constructs that should be studied independently in future research.

Exploring antecedents and outcomes of restricted and repetitive behaviours in autistic children: A thematic analysis of teacher interviews

BackgroundRestricted and repetitive behaviours (RRBs) are a core diagnostic feature in autism, but have received less research compared to other diagnostic areas. Qualitative research with autistic adults has reported both positive and problematic aspects of RRBs, but little qualitative research has been reported to date about the nature and outcomes of RRBs in autistic children. The present study recruited teachers in SEN schools because children have limited ability to self-reflect and report about the functions and outcomes of their behaviours. MethodsThe current study recruited 11 Special Educational Needs (SEN) teachers based in specialist autism schools who were interviewed about the various RRBs and their observed antecedents and outcomes for autistic children in their schools. ResultsThematic analysis revealed two main themes about RRBs in autistic children, one view as positive and one as negative. The positive theme included subthemes of RRBs as enjoyable experiences, self-regulation, and a form of expression. The negative theme included subthemes of being potentially unsafe, disrupting learning, and having a compulsive nature. ConclusionsSEN teachers in the present study observed both positive and negative outcomes of RRBs by autistic children, consistent with reports by autistic adults about their RRBs. The views about positive outcomes challenges previous assumptions that RRBs in autistic children are inherently detrimental and always need to be reduced or eliminated. Instead, the risks of specific RRBs should be considered against their benefits for individual autistic children to differentiate RRBs that serve a positive functional purpose versus those that may be harmful.

The Adult Perceptual Limen of Syllable Segregation in Typically Developing Paediatric Speech

Inappropriate gaps between syllables are one of the core diagnostic features of both childhood apraxia of speech and acquired apraxia of speech. However, little is known about how listeners perceive and identify inappropriate pauses between syllables (gap detection). Only one previous study has investigated the perception of inappropriate pauses between syllables in typical adult speakers and no investigations of gap detection in children's speech have been undertaken. The purpose of this research was to explore the boundaries of listener gap detection to determine at which gap length (duration) a listener can perceive that an inappropriate pause is present in child speech. Listener perception of between-syllable gaps was explored in an experimental design study using the online survey platform Qualtrics. Speech samples were collected from two typically developing children and digitally manipulated to insert gaps between syllables. Adult listeners (n = 84) were recruited and could accurately detect segregation on 80% of presentations at a duration between 100 and 125 ms and could accurately detect segregation on 90% of presentations at a duration between 125 and 150 ms. Listener musical training, gender and age were not correlated with accuracy of detection, but speech pathology training was, albeit weakly. Male speaker gender, and strong onset syllable stress were correlated with increased accuracy compared to female speaker gender and weak onset syllable stress in some gap conditions. The results contribute to our understanding of speech acceptability in CAS and other prosodic disorders and moves towards developing standardised criteria for rating syllable segregation. There may also be implications for computer and artificial intelligence understanding of child speech and automatic detection of disordered speech based on between syllable segregation.

Big Data Approach to Characterize Restricted and Repetitive Behaviors in Autism.

Despite being a core diagnostic feature of autism spectrum disorder (ASD), demographic, developmental and clinical correlates of restricted and repetitive behaviors and interests (RRB) remain poorly characterized. This study aimed to utilize the largest available RRB data set to date to provide a comprehensive characterization of how distinct RRB domains vary according to a range of individual characteristics. Data were obtained from 17,581 children and adolescents with ASD (meanage= 8.24 years, SDage= 4.06) from the Simons Foundation Powering Autism Research for Knowledge cohort. Caregivers completed the Repetitive Behavior Scale-Revised questionnaire as a measure of repetitive motor behaviors, self-injurious behaviors, compulsions, insistence on sameness, and circumscribed interests RRB domains. Caregivers also provided information on children's cognitive functioning, language ability, and social and communication impairments. Male sex was associated with higher severity of repetitive motor behaviors and restricted interests and with lower severity of compulsions and self-injurious behaviors; no sex differences were found for the insistence on sameness domain. Although repetitive motor behaviors showed a mostly linear (negative) association with age, other RRB domains showed more complex and nonlinear pattern of associations. Higher severity of social and communication impairments provided significant independent contribution in predicting higher severity of all RRB domains at the p< .001 level; however, these effects were small (d< 0.25). The strongest of these effects was observed for insistence on sameness (d= 0.24), followed by repetitive motor behaviors (d= 0.21), compulsions (d=0.17), restricted interests (d= 0.14), and self-injurious behaviors (d= 0.12). Findings reported here provide further evidence that RRB subdomains show a somewhat distinct pattern of associations with demographic, developmental, and clinical variables, with a key implication that separate consideration of these domains can help to facilitate efforts to understand diverse ASD etiology and to inform the design of effective interventions.

Language profile of primary progressive aphasia in a linguistically diverse cohort in India

AbstractBackgroundThe accurate characterization of language and semantic memory deficits is crucial for diagnosis of primary progressive aphasia (PPA). In a linguistically diverse society like India, assessment with linguistically appropriate and culturally relevant tools is essential but challenging. This study aimed at developing language and culture specific tests to diagnose PPA and profile cognitive‐linguistic characteristics of a diverse cohort of PPA in India.MethodBased on typical characteristics of Indian languages: free‐word order, rich system of morphology and case‐marking that are features that differentiate Indian languages from English, a language‐specific assessment battery was developed in seven languages: Hindi, Bengali (Indo‐Aryan languages) and Kannada, Telugu, Malayalam and Tamil (Dravidian languages). In the background of the importance of case‐markers in the syntax of Indian languages, a unique syntax assessment test was specifically developed. To evaluate semantic memory, the Indian Semantic Memory battery was developed using stimuli appropriate for a pan‐Indian cultural context. All patients underwent assessment of language proficiency and comprehensive cognitive evaluation by examiners proficient in the language of testing.Result36 patients with PPA: 22 with semantic variant (svPPA), 12 nonfluent variant (nfvPPA) and 2 logopenic variant (lvPPA) participated. The cohort consisted of proficient speakers of seven Indian languages. A particular difficulty in the appropriate use of case markers on the new test of syntax was revealed in nfvPPA compared to svPPA. Further, the core diagnostic feature of ‘agrammatism’ for PPA in English‐speaking nfvPPA was not as dramatic in Indian patients owing to the morphological richness of Indian languages, leading to reduced contrast between fluent versus non‐fluent aphasia. Consistent with diagnosis, a significant reduction in fluency was demonstrated in nfvPPA (p&lt; 0.006 on fluency tasks). Semantic memory was significantly affected in svPPA as revealed on non‐verbal tasks i.e., word‐picture matching (p&lt;0.02)and semantic association task(p&lt;0.01) of Indian Semantic Battery.ConclusionUsing language and culture specific assessment batteries tailored to the Indian context, a comprehensive clinical characteristics in PPA subtypes were identified. The need to re‐define agrammatism with respect to Indian languages with additional weightage to the use of case markers that assist in identifying the PPA subtype was a novel finding.

Short-term trajectories of restricted and repetitive behaviors in minimally verbal children with autism spectrum disorder.

Very little is known about the 30% of children with Autism Spectrum Disorder (ASD) who remain minimally verbal when they enter school. Restricted and repetitive behaviors (RRBs) are well-characterized in younger, preschool, and toddler samples. However, the prevalence and impact of RRBs has not been characterized in older, minimally verbal children. The goal of this study was to characterize this core diagnostic feature in minimally verbal children with ASD ages 5-8 years over a 9-month period to better understand how these behaviors manifest in this crucially understudied population. RRBs were coded from caregiver-child interactions (CCX) at four timepoints. Upon entry into the study, children demonstrated an average of 17 RRBs during a 10-min CCX. The most common category was Verbal. RRBs remained constant over 6 months; however, a slight reduction was observed at the final timepoint. Compared to prior literature on younger samples, minimally verbal children with ASD demonstrated higher rates of RRBs and higher rates of verbal RRBs. Further work is required to understand the function and impact of RRBs in minimally verbal children. LAY ABSTRACT: Approximately one-third of children with autism spectrum disorder (ASD) remain minimally verbal at the time of school entry. In this study, we sought to characterize the presence of restricted and repetitive behaviors (RRBs) in school-aged children (5-8) who were minimally verbal. Compared to prior studies, minimally verbal children with ASD had higher frequencies of RRBs and demonstrated a different profile of behaviors, including more verbal RRBs.

Emotional dysregulation and attention deficit hyperactivity disorder (ADHD)

IntroductionBecause emotional symptoms are common in attention-deficit/hyperactivity disorder (ADHD) patients and associate with much morbidity, some consider it to be a core feature rather than an associated trait.Objectives Assess the possibility that symptoms of emotional dysregulation should be considered as core diagnostic feature of ADHD.Methods It’s a cross sectional study, including 60 children with ADHD and 60 children without ADHD ranging from 6 to 19 years of age (mean age 10.43 years). We defined moderate emotional dysregulation if a child had an aggregate cut-off score of ˃180 on the Anxiety/Depression, Aggression, and Attention scales of the CBCL and severe emotionaldysregulation if a child had an aggregate cut-off score of ˃ 210. This profile was selected because of its conceptual congruence with the clinical concept of emotionaldysregulation.Results Sixty-three percent of children with ADHD had a severe emotional dysregulation versus 12% of controls (P˂0.001). Emotional dysregulation was associated with elevated rates of hyperactivity and impulsivity : Ninety-six percent of the children with hyperactivity-impulsivity, according to the Conners scale, had emotional dysregulation. With a significant correlation between emotional dysregulation and hyperactivity-impulsivity (p = 0.001). Also all children with attentional disorders exhibited emotional dysregulation and a significant correlation between emotional dysregulation and inattention has been found in both groups (p=0.000).ConclusionsEmotional dysregulation is now known to play a causal role regarding ADHD symptomatology. It should therefore be included in future theoretical models of ADHD, as well as in clinical practice when identifying the major impairments in this diagnostic group and when deciding therapeutic strategies.

Stereotypical Behavior in Autism

Restricted, repetitive, and stereotyped forms of behavior are one of three core diagnostic features of autistic disorder (and are a frequent target of behavioral intercessions for children with autism.. Although the fundamental causes of stereotypy are unknown, most scientists in the field believe it comprises a class of operant behaviors maintained by augmentation contingencies.

Temporal Profiles of Social Attention Are Different Across Development in Autistic and Neurotypical People

BackgroundSociocommunicative difficulties, including abnormalities in eye contact, are core diagnostic features of autism spectrum disorder (ASD). Many studies have used eye tracking to measure reduced attention to faces in autistic people; however, most of this work has not taken advantage of eye-tracking temporal resolution to examine temporal profiles of attention. MethodsWe used growth curve analysis to model attention to static social scenes as a function of time in a large (N = 650) sample of autistic participants and neurotypical participants across a wide age range (6–30 years). ResultsThe model yielded distinct temporal profiles of attention to faces in the groups. Initially, both groups showed a relatively high probability of attending to faces, followed by decline after several seconds. The neurotypical participants, however, were significantly more likely to return their attention to faces in the latter part of each 20-second trial, with increasing probability with age. In contrast, the probability of returning to the face in the autistic participants remained low across development. In participants with ASD, more atypical profiles of attention were associated with lower Vineland Adaptive Behavior Scales communication scores and a higher curvature in one data-driven cluster correlated with symptom severity. ConclusionsThese findings show that social attention not only is reduced in ASD, but also differs in its temporal dynamics. The neurotypical participants became more sophisticated in how they deployed their social attention across age, a pattern that was significantly reduced in the participants with ASD, possibly reflecting delayed acquisition of social expertise.

Neural correlates of shared sensory symptoms in autism and attention-deficit/hyperactivity disorder.

Symptoms of autism spectrum disorder and attention-deficit/hyperactivity disorder often co-occur. Among these, sensory impairment, which is a core diagnostic feature of autism spectrum disorder, is often observed in children with attention-deficit/hyperactivity disorder. However, the underlying mechanisms of symptoms that are shared across disorders remain unknown. To examine the neural correlates of sensory symptoms that are associated with autism spectrum disorder and attention-deficit/hyperactivity disorder, we analysed resting-state functional MRI data obtained from 113 people with either autism spectrum disorder or attention-deficit/hyperactivity disorder (n = 78 autism spectrum disorder, mean age = 29.5; n = 35 attention-deficit/hyperactivity disorder, mean age = 31.2) and 96 neurotypical controls (mean age = 30.6, range: 20–55 years) using a cross-sectional study design. First, we used a multi-dimensional approach to examine intrinsic brain functional connectivity related to sensory symptoms in four domains (i.e. low registration, sensation seeking, sensory sensitivity and sensation avoidance), after controlling for age, handedness and head motion. Then, we used a partial least squares correlation to examine the link between sensory symptoms related to intrinsic brain functional connectivity and neurodevelopmental symptoms measured using the Autism Spectrum Quotient and Conners’ Adult Attention-Deficit/Hyperactivity Disorder Rating Scale, regardless of diagnosis. To test whether observed associations were specific to sensory symptoms related to intrinsic brain functional connectivity, we conducted a control analysis using a bootstrap framework. The results indicated that transdiagnostic yet distinct intrinsic brain functional connectivity neural bases varied according to the domain of the examined sensory symptom. Partial least squares correlation analysis revealed two latent components (latent component 1: q < 0.001 and latent component 2: q < 0.001). For latent component 1, a set of intrinsic brain functional connectivity was predominantly associated with neurodevelopmental symptom-related composite score (r = 0.64, P < 0.001), which was significantly correlated with Conners’ Adult Attention-Deficit/Hyperactivity Disorder Rating Scale total T scores (r = −0.99, q < 0.001). For latent component 2, another set of intrinsic brain functional connectivity was positively associated with neurodevelopmental symptom-related composite score (r = 0.58, P < 0.001), which was eventually positively associated with Autism Spectrum Quotient total scores (r = 0.92, q < 0.001). The bootstrap analysis showed that the relationship between intrinsic brain functional connectivity and neurodevelopmental symptoms was relative to sensory symptom-related intrinsic brain functional connectivity (latent component 1: P = 0.003 and latent component 2: P < 0.001). The current results suggest that sensory symptoms in individuals with autism spectrum disorder and those with attention-deficit/hyperactivity disorder have shared neural correlates. The neural correlates of the sensory symptoms were associated with the severity of both autism spectrum disorder and attention-deficit/hyperactivity disorder symptoms, regardless of diagnosis.

Automated recognition of spontaneous facial expression in individuals with autism spectrum disorder: parsing response variability

BackgroundReduction or differences in facial expression are a core diagnostic feature of autism spectrum disorder (ASD), yet evidence regarding the extent of this discrepancy is limited and inconsistent. Use of automated facial expression detection technology enables accurate and efficient tracking of facial expressions that has potential to identify individual response differences.MethodsChildren and adults with ASD (N = 124) and typically developing (TD, N = 41) were shown short clips of “funny videos.” Using automated facial analysis software, we investigated differences between ASD and TD groups and within the ASD group in evidence of facial action unit (AU) activation related to the expression of positive facial expression, in particular, a smile.ResultsIndividuals with ASD on average showed less evidence of facial AUs (AU12, AU6) relating to positive facial expression, compared to the TD group (p < .05, r = − 0.17). Using Gaussian mixture model for clustering, we identified two distinct distributions within the ASD group, which were then compared to the TD group. One subgroup (n = 35), termed “over-responsive,” expressed more intense positive facial expressions in response to the videos than the TD group (p < .001, r = 0.31). The second subgroup (n = 89), (“under-responsive”), displayed fewer, less intense positive facial expressions in response to videos than the TD group (p < .001; r = − 0.36). The over-responsive subgroup differed from the under-responsive subgroup in age and caregiver-reported impulsivity (p < .05, r = 0.21). Reduced expression in the under-responsive, but not the over-responsive group, was related to caregiver-reported social withdrawal (p < .01, r = − 0.3).LimitationsThis exploratory study does not account for multiple comparisons, and future work will have to ascertain the strength and reproducibility of all results. Reduced displays of positive facial expressions do not mean individuals with ASD do not experience positive emotions.ConclusionsIndividuals with ASD differed from the TD group in their facial expressions of positive emotion in response to “funny videos.” Identification of subgroups based on response may help in parsing heterogeneity in ASD and enable targeting of treatment based on subtypes.Trial registrationClinicalTrials.gov, NCT02299700. Registration date: November 24, 2014

Neurophysiological Signatures of Motor Impairment in Patients with Rett Syndrome

Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder due to pathogenic mutations in the MECP2 gene. Motor impairment constitutes the core diagnostic feature of RTT. Preclinical studies have consistently demonstrated alteration of excitation/inhibition (E/I) balance and aberrant synaptic plasticity at the cortical level. We aimed to understand neurobiological mechanisms underlying motor deficit by assessing in vivo synaptic plasticity and E/I balance in the primary motor cortex (M1). In 14 patients with typical RTT, 9 epilepsy control patients, and 11 healthy controls, we applied paired-pulse transcranial magnetic stimulation (TMS) protocols to evaluate the excitation index, a biomarker reflecting the contribution of inhibitory and facilitatory circuits in M1. Intermittent TMS-theta burst stimulation was used to probe long-term potentiation (LTP)-like plasticity in M1. Motor impairment, assessed by ad hoc clinical scales, was correlated with neurophysiological metrics. RTT patients displayed a significant increase of the excitation index (p = 0.003), as demonstrated by the reduction of short-interval intracortical inhibition and increase of intracortical facilitation, suggesting a shift toward cortical excitation likely due to GABAergic dysfunction. Impairment of inhibitory circuits was also confirmed by the reduction of long-interval intracortical inhibition (p = 0.002). LTP-like plasticity in M1 was abolished (p = 0.008) and scaled with motor disability (all p = 0.003). TMS is a method that can be used to assess cortical motor function in RTT patients. Our findings support the introduction of TMS measures in clinical and research settings to monitor the progression of motor deficit and response to treatment. ANN NEUROL 2020;87:763-773.