Brain Alteration Patterns in Children with Duchenne Muscular Dystrophy: A Machine Learning Approach to Magnetic Resonance Imaging.

Background: Duchenne Muscular Dystrophy (DMD) is a genetic disease in which lack of the dystrophin protein causes progressive muscular weakness, cardiomyopathy and respiratory insufficiency. DMD is often associated with other cognitive and behavioral impairments, however the correlation of abnormal dystrophin expression in the central nervous system with brain structure and functioning remains still unclear. Objective: To investigate brain involvement in patients with DMD through a multimodal and multivariate approach accounting for potential comorbidities. Methods: We acquired T1-weighted and Diffusion Tensor Imaging data from 18 patients with DMD and 18 age- and sex-matched controls with similar cognitive and behavioral profiles. Cortical thickness, structure volume, fractional anisotropy and mean diffusivity measures were used in a multivariate analysis performed using a Support Vector Machine classifier accounting for potential comorbidities in patients and controls. Results: the classification experiment significantly discriminates between the two populations (97.2% accuracy) and the forward model weights showed that DMD mostly affects the microstructural integrity of long fiber bundles, in particular in the cerebellar peduncles (bilaterally), in the posterior thalamic radiation (bilaterally), in the fornix and in the medial lemniscus (bilaterally). We also reported a reduced cortical thickness, mainly in the motor cortex, cingulate cortex, hippocampal area and insula. Conclusions: Our study identified a small pattern of alterations in the CNS likely associated with the DMD diagnosis.

Exploring telediagnostic procedures in child neuropsychiatry: addressing ADHD diagnosis and autism symptoms through supervised machine learning.

Recently, there has been an increase in telemedicine applied to child neuropsychiatry, such as the use of online platforms to collect remotely case histories and demographic and behavioral information. In the present proof-of-concept study, we aimed to understand to what extent information parents and teachers provide through online questionnaires overlaps with clinicians' diagnostic conclusions on attention-deficit/hyperactivity disorder (ADHD). Moreover, we intended to explore a possible role that autism spectrum disorders (ASD) symptoms played in this process. We examined parent- and teacher-rated questionnaires collected remotely and an on-site evaluation of intelligence quotients from 342 subjects (18% females), aged 3-16 years, and referred for suspected ADHD. An easily interpretable machine learning model-decision tree (DT)-was built to simulate the clinical process of classifying ADHD/non-ADHD based on collected data. Then, we tested the DT model's predictive accuracy through a cross-validation approach. The DT classifier's performance was compared with those that other machine learning models achieved, such as random forest and support vector machines. Differences in ASD symptoms in the DT-identified classes were tested to address their role in performing a diagnostic error using the DT model. The DT identified the decision rules clinicians adopt to classify an ADHD diagnosis with an 82% accuracy rate. Regarding the cross-validation experiment, our DT model reached a predictive accuracy of 74% that was similar to those of other classification algorithms. The caregiver-reported ADHD core symptom severity proved the most discriminative information for clinicians during the diagnostic decision process. However, ASD symptoms were a confounding factor when ADHD severity had to be established. Telehealth procedures proved effective in obtaining an automated output regarding a diagnostic risk, reducing the time delay between symptom detection and diagnosis. However, this should not be considered an alternative to on-site procedures but rather as automated support for clinical practice, enabling clinicians to allocate further resources to the most complex cases.

Exposure to environmental pollutants and attention-deficit/hyperactivity disorder: an overview of systematic reviews and meta-analyses.

Although heritability estimates suggest a role for genetic components, environmental risk factors have been described as relevant in the etiology of attention deficit/hyperactivity disorder (ADHD). Several studies have investigated the role of toxicological pollution, i.e., air pollution, heavy metals, POPs, and phthalates. Clear evidence for association of ADHD and environmental factors has not been provided yet. To answer this, we have assessed all available systematic reviews and meta-analyses that focused on the association between pollutant exposure and either ADHD diagnosis or symptoms. More than 1800 studies were screened of which 14 found eligible. We found evidence of a significant role for some pollutants, in particular heavy metals and phthalates, in the increased risk of developing ADHD symptoms. However, at the current stage, data from existing literature also do not allow to weight the role of the different environmental pollutants. We also offer a critical examination of the reviews/meta-analyses and provide indications for future studies in this field. PROSPERO registration: CRD42022341496.

A multimodal approach can identify specific motor profiles in autism and attention-deficit/hyperactivity disorder.

It is still unclear whether and to what extent the motor difficulties are specific to autism. This study aimed to determine whether a multimodal assessment of motor skills could accurately discriminate autistic children from attention-deficit/hyperactivity disorder (ADHD) and typically developing (TD) peers. Seventy-five children, aged 7-13, equally divided into three groups, were assessed with the developmental coordination disorder questionnaire (DCDQ), the movement assessment battery for children 2 (MABC2), the sensorimotor subtests of NEPSY-II, and the kinematic analysis of a reach-to-drop task. Principal component analysis (PCA) on DCDQ subscales revealed one factor-Caregiver Report-, whereas MABC2/NEPSY-II scores identified three factors-namely, Object Interception and Balance, Motor Imitation, and Fine-Motor Skills-. Lastly, PCA on kinematic variables identified four factors: PC1, loaded by the parameters of velocity and acceleration throughout the task, PC2 and PC3 involved the temporal parameters of the two submovements, and PC4 accounted for the wrist inclination at ball drop. When comparing autistic and TD children, Caregiver Report and Motor Imitation factors predicted membership with 87.2% of accuracy. In the model comparing ADHD and TD groups, Caregiver Report and Fine-Motor Skills predicted membership with an accuracy of 73.5%. In the last model, the Object Interception and Balance factor differentiated autistic children from ADHD with an accuracy of 73.5%. In line with our previous findings, kinematics did not differentiate school-aged autistic children from ADHD and TD peers. The present findings show that specific motor profiles in autism and ADHD can be isolated with a multimodal investigation of motor skills.

Dynamic balance during walking in people with multiple sclerosis: A cross-sectional study.

Dynamic balance disorders are common impairments in People with Multiple Sclerosis (PwMS) leading to gait disorders and a higher risk of falling. However, the assessment of dynamic balance is still challenging and instrumented indexes provide objective and quantitative data of CoM movement and Base of Support, which are considered that are two key factors describing dynamic balance. This study aims at validating recent instrumented indexes based on the inverted pendulum model and characterizing dynamic balance disorders in PwMS. We clinically assessed 20 PwMS and we collected instrumented gait data through an optoelectronic system. Data from 20 Healthy Subjects (HS) were also considered as normative reference. Margin of Stability by HoF (MoS_Hof) and by Terry (MoS_Terry) at midstance, and Foot Placement Estimator (DFPE) at heel strike were calculated in mediolateral (ML) and anteroposterior (AP) directions, for both less affected and most affected sides for PwMS and for dominant and non-dominant side for HS. MoS_HOF well discriminated between PwMS and HS, followed by MoS_TERRY in ML direction (Mos_HOF: PwMS = 130.0 ± 27.2 mm, HS = 106.5 ± 18.6 mm, p < 0.001, MoS_TERRY: PwMS = 75.1 ± 24.3 mm, HS = 56.5 ± 23.4 mm, p < 0.02). MoS_HOF and MoS_TERRY discriminated between sides in both directions in PwMS. DFPE did not discriminate between groups and sides. Moderate correlations were found between all three indexes and clinical balance scales (from r = 0.02 to r = 0.66), energy recovery (from r = -0.77 to r = -0.11), single stance time (from r = -0.11 to r = 0.80) and step length (from r = -0.83 to r = -0.20). MoS_HOF resulted in the best index to describe dynamic balance disorders in PwMS: they keep CoM position far from the lateral and as close as possible to the anterior boundary of the Base of Support as preventive strategies to control balance perturbations. Furthermore, PwMS seem to use different preventive strategies in accordance with the specific lower limb impairments. This alters the physiological gait mechanisms increasing the energy expenditure and decreasing gait quality and dynamic balance.

Dynamics of Hole Singlet-Triplet Qubits with Large g-Factor Differences.

The spin-orbit interaction permits to control the state of a spin qubit via electric fields. For holes it is particularly strong, allowing for fast all electrical qubit manipulation, and yet an in-depth understanding of this interaction in hole systems is missing. Here we investigate, experimentally and theoretically, the effect of the cubic Rashba spin-orbit interaction on the mixing of the spin states by studying singlet-triplet oscillations in a planar Ge hole double quantum dot. Landau-Zener sweeps at different magnetic field directions allow us to disentangle the effects of the spin-orbit induced spin-flip term from those caused by strongly site-dependent and anisotropic quantum dot g tensors. Our work, therefore, provides new insights into the hole spin-orbit interaction, necessary for optimizing future qubit experiments.

Understanding feeding problems in autistic children: Exploring the interplay between internalizing symptoms and sensory features.

LAY ABSTRACT: This study adds to a growing body of research documenting feeding problems in autistic children. Our results indicate that children aged 1.5-5 years with feeding problems may present with elevated internalizing difficulties and alterations in sensory processing when compared to same-age children without feeding problems. Our study also proposes that sensory processing may be an important, mediating factor in the relationship between autism features and feeding problems. The present work suggests, therefore, that implementers should thoroughly consider the sensory profile of autistic children prior to intervening on feeding behaviors. In particular, based on these preliminary findings, feeding interventions could benefit from environments designed to support children who can find them noisy and overwhelming.

Smoothness of movement in idiopathic cervical dystonia.

Smoothness (i.e. non-intermittency) of movement is a clinically important property of the voluntary movement with accuracy and proper speed. Resting head position and head voluntary movements are impaired in cervical dystonia. The current work aims to evaluate if the smoothness of voluntary head rotations is reduced in this disease. Twenty-six cervical dystonia patients and 26 controls completed rightward and leftward head rotations. Patients' movements were differentiated into "towards-dystonia" (rotation accentuated the torticollis) and "away-dystonia". Smoothness was quantified by the angular jerk and arc length of the spectrum of angular speed (i.e. SPARC, arbitrary units). Movement amplitude (mean, 95% CI) on the horizontal plane was larger in controls (63.8°, 58.3°-69.2°) than patients when moving towards-dystonia (52.8°, 46.3°-59.4°; P = 0.006). Controls' movements (49.4°/s, 41.9-56.9°/s) were faster than movements towards-dystonia (31.6°/s, 25.2-37.9°/s; P < 0.001) and away-dystonia (29.2°/s, 22.9-35.5°/s; P < 0.001). After taking into account the different amplitude and speed, SPARC-derived (but not jerk-derived) indices showed reduced smoothness in patients rotating away-dystonia (1.48, 1.35-1.61) compared to controls (1.88, 1.72-2.03; P < 0.001). Poor smoothness is a motor disturbance independent of movement amplitude and speed in cervical dystonia. Therefore, it should be assessed when evaluating this disease, its progression, and treatments.

Evidence of Josephson Coupling in a Few-Layer Black Phosphorus Planar Josephson Junction.

Setting up strong Josephson coupling in van der Waals materials in close proximity to superconductors offers several opportunities both to inspect fundamental physics and to develop cryogenic quantum technologies. Here we show evidence of Josephson coupling in a planar few-layer black phosphorus junction. The planar geometry allows us to probe the junction behavior by means of external gates, at different carrier concentrations. Clear signatures of Josephson coupling are demonstrated by measuring supercurrent flow through the junction at milli-Kelvin temperatures. Manifestation of a Fraunhofer pattern with a transverse magnetic field is also reported, confirming the Josephson coupling. These findings represent evidence of proximity Josephson coupling in a planar junction based on a van der Waals material beyond graphene and will expedite further studies, exploiting the peculiar properties of exfoliated black phosphorus thin flakes.

Patterns of Response to Methylphenidate Administration in Children with ADHD: A Personalized Medicine Approach through Clustering Analysis.

Individual responses to methylphenidate (MPH) can significantly differ in children with attention-deficit/hyperactivity disorder (ADHD) in terms of the extent of clinical amelioration, optimal dosage needed, possible side effects, and short- and long-term duration of the benefits. In the present repeated-measures observational study, we undertook a proof-of-concept study to determine whether clustering analysis could be useful to characterize different clusters of responses to MPH in children with ADHD. We recruited 33 children with ADHD who underwent a comprehensive clinical, cognitive, and neurophysiological assessment before and after one month of MPH treatment. Symptomatology changes were assessed by parents and clinicians. The neuropsychological measures used comprised pen-and-paper and computerized tasks. Functional near-infrared spectroscopy was used to measure cortical hemodynamic activation during an attentional task. We developed an unsupervised machine learning algorithm to characterize the possible clusters of responses to MPH in our multimodal data. A symptomatology improvement was observed for both clinical and neuropsychological measures. Our model identified distinct clusters of amelioration that were related to symptom severity and visual-attentional performances. The present findings provide preliminary evidence that clustering analysis can potentially be useful in identifying different responses to MPH in children with ADHD, highlighting the importance of a personalized medicine approach within the clinical framework.

Strategies for maintaining dynamic balance in persons with neurological disorders during overground walking.

Maintaining a stable gait requires a dynamic balance control, that can be altered in persons with Multiple Sclerosis (MS), Stroke (ST), and Parkinson's disease (PD). The understanding of the strategy for Center of Mass (CoM) positioning adopted by patients during walking is important to be able to program treatments aimed at improving gait control and preventing falls. Forty-four persons with a mild-to-moderate neurological disorder (20 with MS, 14 with ST, 10 with PD) underwent clinical examination and gait analysis. Ten Healthy Subjects (HS) walking at matched speed provided the normative data. Dynamic balance was assessed using the margin of stability (MoS). It was calculated as the distance between the extrapolated Center of Pressure and the extrapolated CoM at mid-stance. The MoS values for lower limbs were calculated in patients and compared with speed-matched values of HS. Persons with neurological disorder showed increased MoS in the medio-lateral direction with respect to HS. Within-group comparison analysis showed a symmetry between lower limbs in HS (Mean (95%CI) [mm], dominant vs non-dominant limb, 43.3 (31.9-54.6) vs 42.9 (28.8-56.9)) and PD (less affected vs more affected limb, 71.1 (59.8-82.5) vs 72.5 (58.5-86.6)), while a significant asymmetry was found in MS (54.4 (46.4-62.4) vs 81.1 (71.2-91.1)) and ST (52.1 (42.6-61.7) vs 74.7 (62.8-86.6)) participants. The history of falls was comparable among PD, MS, and ST groups, and the MoS in the frontal plane showed a strong correlation with these records. Objective assessment of MoS revealed pathology-specific strategies showing different impacts in MS, ST, and PD on the ability to control CoM information to manage the balance between limbs during gait. MoS evaluation will provide useful information to address a tailored rehabilitation program and to monitor disease progression.

A singlet-triplet hole spin qubit in planar Ge.

Spin qubits are considered to be among the most promising candidates for building a quantum processor. Group IV hole spin qubits are particularly interesting owing to their ease of operation and compatibility with Si technology. In addition, Ge offers the option for monolithic superconductor-semiconductor integration. Here, we demonstrate a hole spin qubit operating at fields below 10 mT, the critical field of Al, by exploiting the large out-of-plane hole g-factors in planar Ge and by encoding the qubit into the singlet-triplet states of a double quantum dot. We observe electrically controlled g-factor difference-driven and exchange-driven rotations with tunable frequencies exceeding 100 MHz and dephasing times of 1 µs, which we extend beyond 150 µs using echo techniques. These results demonstrate that Ge hole singlet-triplet qubits are competing with state-of-the-art GaAs and Si singlet-triplet qubits. In addition, their rotation frequencies and coherence are comparable with those of Ge single spin qubits, but singlet-triplet qubits can be operated at much lower fields, emphasizing their potential for on-chip integration with superconducting technologies.

Characterization of Autism Spectrum Disorder (ASD) subtypes based on the relationship between motor skills and social communication abilities.

Motor abnormalities are generally observed in autism spectrum disorder (ASD), and motor difficulties are certainly evident during the early years of life and may thus precede social-communication impairments. The main aim of the present study was to examine ASD subtypes based on the relationship between motor skills and social communication abilities. Motor skills and social communication abilities were evaluated through the Movement Assessment Battery for Children-Second Edition, the Autism Diagnostic Observation Schedule-Second Version and the Psychoeducational Profile-Third Edition. In addition, social communication abilities were classified according to the Autism Classification System of Functioning: Social Communication-ACSF:SC criteria. We found that children with ASD presented poorer motor skills than their TD peers, and motor impairments correlated with poorer social communication abilities in children with ASD. In addition, children with lower social and communication functioning showed a more prominent impairment in manual dexterity and fine motor skills than children with better social and communication functioning. In conclusion, we suggest that stratifying children with ASD based on motor and social endophenotypes may be useful to understand the neurobiological mechanisms of ASD and lead to new types of treatment.

A multimethod approach to assessing motor skills in boys and girls with autism spectrum disorder.

LAY ABSTRACT: Motor peculiarities are often reported in children with autism spectrum disorder and may predict subsequent adaptive functioning and quality of life. Although the sex bias in the prevalence of the disorder is well documented, little is known about differences in motor profile in males and females with autism spectrum disorder. Our goal was to study differences in motor functioning of boys and girls with autism spectrum disorder aged 3-11 years compared with typically developing children. Their motor performances were evaluated using a multimethod approach, including standardized motor tests, caregiver reports, and a detailed motion capture analysis of a simple reach-to-drop movement. We found that, irrespective of sex, children with autism spectrum disorder had worse scores than typically developing children on standardized tests and on caregiver reports. Interestingly, girls with autism spectrum disorder, but not boys, presented altered motor anticipation in reach-to-drop. Our findings emphasize the need for more sex-specific assessment of motor function in autism spectrum disorder.

Fundamental Motor Skills Intervention for Children with Autism Spectrum Disorder: A 10-Year Narrative Review.

In the past decade, converging evidence has suggested that motor impairment is one of the most consistent markers, alongside sociocommunicative difficulties, for autism spectrum disorder (ASD). Indeed, widespread anomalies of movement have been described in the ASD context. These motor abnormalities could have critical implications for subsequent cognitive and social development. Nevertheless, this area of development is particularly underexamined in the autism-related context, and early intervention programs commonly focus on the core symptoms of the condition. In the present work, we review and discuss the findings from recent studies that investigated the effect of interventions regarding fundamental motor skills in autistic children. Although the limited nature of the literature prevents researchers from drawing definitive conclusions, the results from the studies discussed here demonstrated potentially significant improvements in the motor abilities of autistic children after the interventions. Only a subset of the reviewed studies explored possible changes in the sociocommunicative domain after the motor skills improvements, and they had not concordant, although promising, conclusions. Overall, in consideration of the well-documented motor impairment people with the condition, the present findings highlight the importance of including motor skills training within the rehabilitation programs designed for autistic children. Furthermore, this narrative review encourages future interventional trials to consider motor skills as a possible target for reducing activity limitations and participation restrictions of autistic children.

Hemodynamic and behavioral peculiarities in response to emotional stimuli in children with attention deficit hyperactivity disorder: An fNIRS study.

BACKGROUND: Children with attention deficit hyperactivity disorder (ADHD) exhibit behavioral inhibition deficits, which often lead to emotional dysregulation (ED) affecting individual ability to control emotions and behavioral responses. In ADHD, ED is associated with poor outcomes and comorbidities, with both externalizing and internalizing disorders. This work aims to evaluate sensitivity to emotional stimuli in children with ADHD using functional Near Infrared Spectroscopy (fNIRS). METHODS: During frontal fNIRS recording, 20 children with ADHD and 25 typically developing (TD) peers performed a visual continuous performance task with stimuli of different emotional content (i.e., positive, negative, neutral, and control stimuli without emotional content). This is a cognitive task designed to evaluate the ability to recognize emotional stimuli and to deal with emotional interference. RESULTS: The ADHD sample showed more variability in response time to stimuli and more false alarms compared to TD group. fNIRS data showed between-group differences in right prefrontal and frontal cortices, with wider hemoglobin concentration changes in the TD group, during positive, negative, and neutral conditions. LIMITATIONS: Owing to the limited possibility of near infrared light to penetrate tissue, fNIRS can only measure cortical activations, while it would be of interest to identify the subcortical areas linked to emotional processing, too. CONCLUSIONS: Findings suggest the presence of emotional processing deficits in children with ADHD, as suggested by poor performances on the e-CPT task, and of peculiar sensitivity to emotional stimuli, linked to atypical hemodynamics of right prefrontal and frontal areas.

Improved Gait of Persons With Multiple Sclerosis After Rehabilitation: Effects on Lower Limb Muscle Synergies, Push-Off, and Toe-Clearance.

Introduction: Persons with MS (PwMS) have markedly reduced push-off and toe-clearance during gait compared to healthy subjects (HS). These deficits may result from alterations in neuromotor control at the ankle. To optimize rehabilitation interventions for PwMS, a crucial step is to evaluate if and how altered neuromotor control, as represented by muscle synergies, improves with rehabilitation. In this study we investigated changes in ankle motor control and associated biomechanical parameters during gait in PwMS, occurring with increase in speed after gait rehabilitation. Methods: 3D motion and EMG data were collected while 11 PwMS (age 50.3 + 11.1; EDSS 5.2 + 1.2) walked overground at self-selected speed before (T0) and after 20 sessions (T1) of intensive treadmill training. Muscle synergies were extracted using non-negative matrix factorization. Gait parameters were computed according to the LAMB protocol. Pearson's correlation coefficient was used to evaluate the similarity of motor modules between PwMS and HS. To assess differences in distal module activations representing neuromotor control at the ankle [Forward Propulsion (FPM) and Ground Clearance modules (GCM)], each module's activation timing was integrated over 100% of the gait cycle and the activation percentage index (API) was computed in six phases. Ten age matched HS provided two separate speed-matched normative datasets for T0 and T1. For speed independent comparison for the PwMs Z scores were calculated for all their gait variables. Results: In PwMS velocity increased significantly from T0 to T1 (0.74-0.90 m/s, p < 0.05). The activation profiles (API) of FPM and GCM of PwMS improved in pre-swing (p < 0.05): FPM (Mean [95% CI] [%]: T0: 12.5 [5.7-19.3] vs. T1: 9.0 [2.7-15.3]); GCM (T0: 26.7 [18.2-35.3] vs. T1: 24.5 [18.2-30.7]). This was associated with an increase in toe clearance (80.3 to 103.6 mm, p < 0.05) and a higher ankle power peak in pre-swing (1.53-1.93 W/kg, p < 0.05). Conclusion: Increased gait speed of PwMS after intensive gait training was consistent with improvements in spatio-temporal gait parameters. The most important finding of this study was the re-organization of distal leg modules related to neurophysiological changes induced by rehabilitation. This was associated with an improved ankle performance.

The utility of NIRS technology for exploring emotional processing in children.

BACKGROUND: Deficits in emotional processing and, in particular, in emotional self-regulation represent non-specific risk factors for transdiagnostic poor outcomes. Researches have been focusing on the investigation of possible emotional processing and regulation biomarkers. The present brief review of the literature aims to evaluate whether NIRS signal might be one of them. METHODS: We reviewed 8 original articles investigating children's hemodynamic response to emotional tasks using NIRS, or exploring the association between NIRS response to cognitive tasks and behavioral emotional regulation. RESULTS: All the works revised found significant associations between NIRS data and emotional indexes. Furthermore, significant hemodynamic response is found in different age-groups (3-12 years of age), suggesting that cortical response to emotional processing as measured by NIRS is a marker consistently recognizable throughout the development. LIMITATIONS: Given that the studies in this field were still limited and used heterogeneous protocols, addressed different functions or aspects of emotional processing, these results are preliminary. CONCLUSIONS: NIRS seems a reliable tool to describe brain activation during emotional processing and regulation. Moreover, it seems to be particularly useful in studies including either developmental-aged participants or clinical samples, due to its clear advantages and non-intrusiveness, offering a potential marker for deficits in emotional processing and regulation.

Differences in Developmental Functioning Profiles Between Male and Female Preschoolers Children With Autism Spectrum Disorder.

This study investigated differences in clinical symptoms and developmental functioning profiles as well as sex-specific correlations of clinical characteristics and communication abilities, motor skills, and maladaptive behaviors in male and female preschoolers with autism spectrum disorder (ASD). Fifty-two females (mean age 4.5 ± 2.16 years old) and 62 males (mean age 4.2 ± 1.17 years old) with ASD were enrolled and assessed by measures including the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Psychoeducational Profile-Third Edition (PEP-3). We found intellectual disability in 91.2% of the children. While preschoolers with ASD showed comparable severity of restricted and repetitive behaviors (P = 0.17), females with ASD were less severely affected than age and intelligence quotient-matched males with ASD in the ADOS-2 social affect domain (P value = 0.001) and calibrated severity scores (P = 0.002). Interestingly, sex-specific linear regressions revealed that fine motor skills were predictive of impaired social affect in males but not in females. Specifically, motor skills might be the core feature for sex differences in ASD. Although preliminary, this finding suggests the need for more sex-specific diagnostic and intervention strategies in order to improve early identification efforts and specific intervention targets. LAY SUMMARY: Little is known about differences in developmental and functional profiles in males and females with autism spectrum disorder (ASD). We found important similarities and differences in the core ASD symptoms between male and female preschoolers. In addition, fine motor skills seem to predict social affect impairment and ASD symptom severity in males with ASD. Autism Res 2020, 13: 1537-1547. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.