Objective: Sensory behaviors are common clinically relevant features of many neurodevelopmental disorders including Autism. However, existing assessments critically lack granularity in evaluating hypersensitivity and hyposensitivity, particularly in relation to stimulus intensity. We address this gap by developing the Sensory Response Questionnaire Phenotyper (SRQP), a parent questionnaire that comprehensively assesses sensory behaviors across five sensory modalities. Here we report the development of the SRQP, validation against established tools and assessment of its effectiveness in identifying nuanced sensory processing patterns in children with Autism.Methods: A convenience sample of 317 participants (57 with Autism, 260 typically developing) aged 3-17 years were enrolled in a cross-sectional study. The SRQP’s psychometric properties were analyzed using classical test theory (CTT), and item response theory (IRT). Statistical tests were used to evaluate patterns of sensory processing from SRQP results.Results: Data from 271 participants were included. The SRQP demonstrated strong psychometric properties: a receiver operating characteristic (ROC) curve analysis identified 37 as the cut-off value for most accurately distinguishing between typical and atypical responses on the SRQP (sensitivity 0.75, specificity 0.79, AUC 0.87). Total but not modality-specific hyper vs hyposensitivity scores were moderately correlated (ρ = .5). Responses to high-intensity stimuli were not correlated with responses to low-intensity stimuli for auditory, visual, taste, or tactile hyposensitivity (ρ < .4).Conclusion: The SRQP is a new validated parent questionnaire to assess multi-dimensional properties of sensory behaviors. Stimulus intensity is an important parameter of sensory behaviors that should be accounted for in future models.

This study seeks to examine the relationship between anxiety-symptom severity and sleep behaviors in autistic children receiving cognitive behavioral therapy (CBT). We conducted a secondary-data analysis from a sample of 93 autistic youth, 4 to 14 years, participating in 24 weeks of CBT. Clinicians completed the Pediatric Anxiety Rating Scale (PARS) and parents completed the Children’s Sleep Habits Questionnaire, Abbreviated/Short Form (CSHQ-SF) at baseline, mid-treatment, post-treatment and 3 months post-treatment. Mediation analysis evaluated the role of anxiety symptoms in mediating the effect of time in treatment on sleep. There was a negative association between time in treatment and scores on the CSHQ-SF (b = − 3.23, SE = 0.493, t = − 6.553, p < 0.001). Increased time in treatment was associated with decreased anxiety (b = − 4.66, SE = 0.405, t = − 11.507, p < 0.001), and anxiety symptoms decreased with CSHQ-SF scores (b = 0.322, SE = 0.112, t = 2.869, p = 0.005). The indirect effect of time in treatment on CSHQ-SF scores through PARS reduction was negative, but not statistically significant. Increased time in CBT was associated with decreased anxiety severity and improved sleep behaviors. Reductions in anxiety symptoms may mediate improvements in sleep problems, but larger sample sizes are necessary to explore this further.

Abstract Background Peer review is essential to the advancement of knowledge. However, training on how to conduct peer review is limited, unorganized, and not well studied. Thus, we sought to determine if a structured mentored peer-review program improved peer review training as measured by multiple quantitative and qualitative assessments. Methods This pre-post intervention study enrolled 55 mentees across 5 cohorts from 2020 to 2023. Each cohort completed pre-program evaluations, participated in 2 mentored reviews, and completed post-program evaluations over 6 months. Mentors and mentees completed pre-program demographic and review experience questionnaires. Outcome measures included (1) total and sub-scores on the modified Review Quality Index (mRQI) applied to the same pre-selected research manuscript reviewed by mentees both pre and post intervention, (2) mentee self-perceived comfort with and understanding of the review process using a custom questionnaire, and (3) mentor satisfaction surveys. Pre- and post-program measures were compared using the Wilcoxon signed-rank test. Results Post-program total modified RQI score (median (IQR) = 31 (26.3–35.8)) was higher than pre-program total score (26.6 (19.7–29.7)) for the 42 mentees who completed both pre- and post-program reviews. Mentees reported improved perception of review (median (IQR) pre = 4 (3–4), post = 5 (4–5)) and editorial processes (pre = 3 (2–4), post = 4 (4–5)) as well as self-perceived confidence in completing an independent review of both scientific (median (IQR) pre = 2 (2–3), post = 4 (4–4)) and non-scientific (pre = 3 (2–4), post = 4 (4–5)) manuscripts following program participation. p < 0.0001 for all scores noted. Mentors reported high scores for enjoyment (median (range) 5/5 (3–5)) and interest in repeat participation (5/5 (2–5)). Conclusions A 6-month structured mentored-review program including 2 mentored reviews improves peer review training as measured by the modified RQI as well as participant self-perceived understanding of publication science with high mentor satisfaction.

AIMTo estimate prevalence of sensory symptoms in people with cerebral palsy (CP) across the lifespan.METHODIn this cross-sectional study, the self-reported Sensory Processing Scale Inventory (SPS-I) was administered via REDCap between 2/1/22 and 8/15/22 to people with CP or their caregivers enrolled in the online MyCP Community Registry. We determined the association between SPS-I scores and age (Pearson correlation) and functional status as assessed using five validated functional classification systems for CP (ANOVA). We hypothesized that sensory symptoms would differ between younger and older individuals with CP.RESULTSOf 155 responses (28% response rate, age 1-76 years, 34% male), 97% reported at least one bothersome sensory symptom. Total sensory symptoms decreased with age (R2=0.12, p<0.0001), driven by decreases in hyposensitivity symptoms (R2=0.32, p<0.0001), primarily tactile hyposensitivity (R2=0.29, p<0.0001). Sensory symptoms increased with greater functional impairment across all functional domains (ANOVA, p<0.0001). However, the age-specific decrease in hypo-sensitivities was most pronounced in people with the greatest gross motor functional impairment (R2=0.70, p=0.0004).INTERPRETATIONOur findings suggest that hypo-sensitivity, primarily tactile sensitivity, decreases with age in people with CP. Future work should assess whether decreased hyposensitivity contributes to other age-related changes in CP like increased pain.

The methyl CpG-binding protein-2 (MECP2) gene is located on the Xq28 region. Loss of function mutations or increased copies of MECP2 result in Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. Individuals with both disorders exhibit overlapping autism symptoms, yet few studies have dissected the differences between these gene dosage sensitive disorders. Further, research examining sensory processing patterns in persons with RTT and MDS is largely absent. Thus, the goal of this study was to analyze and compare sensory processing patterns in persons with RTT and MDS. Towards this goal, caregivers of 50 female individuals with RTT and 122 male individuals with MDS, between 1 and 46 years of age, completed a standardized measure of sensory processing, the Sensory Experiences Questionnaire. Patterns detected in both disorders were compared against each other and against normative values. We found sensory processing abnormalities for both hyper- and hypo-sensitivity in both groups. Interestingly, abnormalities in MDS were more pronounced compared with in RTT, particularly with items concerning hypersensitivity and sensory seeking, but not hyposensitivity. Individuals with MDS also exhibited greater sensory symptoms compared with RTT in the areas of tactile and vestibular sensory processing and for both social and nonsocial stimuli. This study provides a first description of sensory symptoms in individuals with RTT and individuals with MDS. Similar to other neurodevelopmental disorders, a variety of sensory processing abnormalities was found. These findings reveal a first insight into sensory processing abnormalities caused by a dosage sensitive gene and may ultimately help guide therapeutic approaches for these disorders.

We describe the clinical course, including neuroimaging at multiple time points, of a patient who presented with acute-onset numbness and weakness due to hemiplegic migraine, illustrating perfusion alterations coinciding with symptom changes.

Cotransmission, meaning the release of multiple neurotransmitters from one synapse, allows for increased diversity of signaling in the brain. Dopamine (DA) and gamma-aminobutyric acid (GABA) are known to coexpress in many regions such as the olfactory bulb and the ventral tegmental area. Tuberoinfundibular dopaminergic neurons (TIDA) in the arcuate nucleus of the hypothalamus (Arc) project to the median eminence (ME) and regulate prolactin release from the pituitary, and prior work suggests dopaminergic Arc neurons also cotransmit GABA. However, the extent of cotransmission, and the projection patterns of these neurons have not been fully revealed. Here, we used a genetic intersectional reporter expression approach to selectively label cells that express both tyrosine hydroxylase (TH) and vesicular GABA transporter (VGAT). Through this approach, we identified cells capable of both DA and GABA cotransmission in the Arc, periventricular (Pe), paraventricular (Pa), ventromedial, and the dorsolateral hypothalamic nuclei, in addition to a novel population in the caudate putamen. The highest density of labeled cells was in the Arc, 6.68% of DAPI-labeled cells at Bregma -2.06 mm, and in the Pe, 2.83% of DAPI-labeled cells at Bregma -1.94 mm. Next, we evaluated the projections of these DA/GABA cells by injecting an mCherry virus that fluoresces in DA/GABA cells. We observed a cotransmitting DA/GABA population, with projections within the Arc, and to the Pa and ME. These data suggest DA/GABA Arc neurons are involved in prolactin release as a subset of TIDA neurons. Further investigation will elucidate the interactions of dopamine and GABA in the hypothalamus.

Abstract Background: Peer review is essential to the advancement of knowledge. However, training on how to conduct peer review is limited, unorganized, and not well studied. Thus, we sought to determine if a structured mentored peer-review program improves the quality of peer review as measured by quantitative assessment of peer review of a standardized manuscript. Methods: This pre-post intervention study enrolled 55 mentees across 5 cohorts from 2020 to 2023. Each cohort completed pre-program evaluations, participated in two mentored reviews, and completed post-program evaluations over 6 months. The primary outcome measured was total score on the modified Review Quality Index (RQI). Secondary outcomes included participant-reported comfort with and understanding of the review process as well RQI subscores. Pre- and post-program measures were compared using the Wilcoxon test. The a priori hypothesis was that mentored review would improve peer review quality. Results: 42 mentees completed both pre- and post-program reviews of a standardized manuscript. For these participants, post-program total modified RQI score (median (IQR) = 31 (26.25-35.75)) was significantly higher than pre-program total scores (26.59 (19.67-29.46)). 53 mentees completed both pre- and post-program surveys which showed improved participant perceptions of the review (median (IQR) scores pre = 4 (3-4) , post =5 (4-5)) and editorial processes (pre = 3 (2-4), post = 4 (4-5)). In addition, confidence in completing an independent review of both scientific (median (IQR) scores pre = 2 (2-3), post = 4 (4-4)) and non-scientific (pre = 3 (2-4) , post = 4 (4-5)) manuscripts significantly increased following program participation. p < 0.0001 for all scores noted above. Conclusions: A six-month structured mentored-review program including 2 mentored reviews improves peer review quality as measured by the modified RQI as well as participant understanding of publication science.

Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial short-axon cells in the olfactory bulb release both dopamine and γ-aminobutyric acid (GABA), yet the specific targets of these neurotransmitters and their respective roles in olfaction have remained unknown. Here, we implement intersectional genetics in mice to selectively block GABA or dopamine release from superficial short-axon cells to identify their distinct cellular targets, impact on circuit function, and behavioral contribution of each neurotransmitter toward olfactory behaviors. We provide functional and anatomical evidence for divergent superficial short-axon cell signaling onto downstream neurons to shape patterns of mitral cell firing that contribute to olfactory-related behaviors.

Thursday, April 7May 3, 2022Free AccessA Formal Mentored Peer Review Program Quantitatively Improves the Quality of Peer Review (S34.001)Whitley Aamodt, Ariel Lyons-Warren, Kathleen Pieper, and Roy StrowdAuthors Info & AffiliationsMay 3, 2022 issue98 (18_supplement)https://doi.org/10.1212/WNL.98.18_supplement.3043 Letters to the Editor

Over the past 18 years, the Neurology Resident & Fellow Section (RFS) has published high-quality manuscripts with a focus on topics relevant to neurologists in training. The mission of the RFS is to disseminate work on topics related to clinical neurology for trainees, with the primary goal of helping current trainees become better neurologists. Most RFS publications are case-based manuscripts that highlight important clinical points, whereas other articles are a forum for students, residents, fellows, and faculty to share their insights and experiences.

Over the past 18 years, the Neurology Resident & Fellow Section (RFS) has published high-quality manuscripts with a focus on topics relevant to neurologists in training. The mission of the RFS is to disseminate work on topics related to clinical neurology for trainees, with the primary goal of helping current trainees become better neurologists. Most RFS publications are case-based manuscripts that highlight important clinical points, whereas other articles are a forum for students, residents, fellows, and faculty to share their insights and experiences.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 1 in 44 children in the United States.1 While genetic factors have long been implicated in ASD,2 the complex interactions of environmental and genetic influences remain unclear. Developing a detailed understanding of ASD risk factors is important to allow prompt and early diagnosis, to provide evidence-based prognostic information to families, and to increase our understanding of underlying brain mechanisms contributing to ASD features. Pediatric ischemic stroke is similarly heterogeneous and potentially debilitating—albeit far less common than ASD with an incidence of 5.6 per 100,000.3 While it is well established that pediatric ischemic stroke is a risk factor for future neurologic conditions, including epilepsy4 and cerebral palsy,5 both of which are independently associated with ASD, the risk of ASD after pediatric ischemic stroke was previously unknown.

Autism spectrum disorder is a common, heterogeneous neurodevelopmental disorder lacking targeted treatments. Additional features include restricted, repetitive patterns of behaviors and differences in sensory processing. We hypothesized that detailed sensory features including modality specific hyper- and hypo-sensitivity could be used to identify clinically recognizable subgroups with unique underlying gene variants. Participants included 378 individuals with a clinical diagnosis of autism spectrum disorder who contributed Short Sensory Profile data assessing the frequency of sensory behaviors and whole genome sequencing results to the Autism Speaks' MSSNG database. Sensory phenotypes in this cohort were not randomly distributed with 10 patterns describing 43% (162/378) of participants. Cross comparison of two independent cluster analyses on sensory responses identified six distinct sensory-based subgroups. We then characterized subgroups by calculating the percent of patients in each subgroup who had variants with a Combined Annotation Dependent Depletion (CADD) score of 15 or greater in each of 24,896 genes. Each subgroup exhibited a unique pattern of genes with a high frequency of variants. These results support the use of sensory features to identify autism spectrum disorder subgroups with shared genetic variants.

Sensory processing differences are an established feature of both syndromic and non-syndromic Autism Spectrum Disorders (ASDs). Significant work has been carried out to characterize and classify specific sensory profiles in non-syndromic autism. However, it is not known if syndromic autism disorders, such as Phelan-McDermid Syndrome (PMD) or SYNGAP1-related Intellectual Disability (SYNGAP1-ID), have unique sensory phenotypes. Understanding the sensory features of these disorders is important for providing appropriate care and for understanding their underlying mechanisms. Our objective in this work was to determine the sensory processing abnormalities present in two syndromic ASDs: Phelan-McDermid Syndrome and SYNGAP1-related Intellectual Disability. Using a standardized instrument, the Short Sensory Profile-2, we characterized sensory features in 41 patients with PMD and 24 patients with SYNGAP1-ID, and sub-scores were then calculated for seeking, avoiding, sensitivity and registration, as well as overall sensory and behavior scores. We found both patient groups exhibited atypical sensory features, including high scores in the areas of avoiding and seeking. Thus, we discovered significant sensory processing abnormalities are common in these syndromic ASDs. Measurements of sensory processing could serve as useful clinical endpoints for trials of novel therapeutics for these populations.

To develop a mentored program for training residents and fellows to conduct high-quality peer review.