Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of ...these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000 Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a ‘core’ abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate ‘neural tone’ and an inability to rapidly return to a resting state prior to the next stimulus.
Background Auditory processing abnormalities are frequently observed in autism spectrum disorders (ASD), and these abnormalities may have sequelae in terms of clinical language impairment (LI). The ...present study assessed associations between language impairment and the amplitude and latency of the superior temporal gyrus magnetic mismatch field (MMF) in response to changes in an auditory stream of tones or vowels. Methods Fifty-one children with ASD, and 27 neurotypical control subjects, all aged 6 to 15 years, underwent neuropsychological evaluation, including tests of language function, as well as magnetoencephalographic recording during presentation of tones and vowels. The MMF was identified in the difference waveform obtained from subtraction of responses to standard from deviant stimuli. Results Magnetic mismatch field latency was significantly prolonged ( p < .001) in children with ASD, compared with neurotypical control subjects. Furthermore, this delay was most pronounced (∼50 msec) in children with concomitant LI, with significant differences in latency between children with ASD with LI and those without ( p < .01). Receiver operator characteristic analysis indicated a sensitivity of 82.4% and specificity of 71.2% for diagnosing LI based on MMF latency. Conclusions Neural correlates of auditory change detection (the MMF) are significantly delayed in children with ASD, and especially those with concomitant LI, suggesting a neurobiological basis as well as a clinical biomarker for LI in ASD.
Motivated by auditory and speech deficits in autism spectrum disorders (ASD), the frequency dependence of superior temporal gyrus (STG) 50 msec (M50) and 100 msec (M100) neuromagnetic auditory evoked ...field responses in children with ASD and typically developing controls were evaluated. Whole‐cortex magnetoencephalography (MEG) was obtained from 17 typically developing children and 25 children with ASD. Subjects were presented tones with frequencies of 200, 300, 500, and 1,000 Hz, and left and right STG M50 and M100 STG activity was examined. No M50 latency or amplitude Group differences were observed. In the right hemisphere, a Group×Frequency ANOVA on M100 latency produced a main effect for Group (P=0.01), with an average M100 latency delay of 11 msec in children with ASD. In addition, only in the control group was the expected association of earlier M100 latencies in older than younger children observed. Group latency differences remained significant when hierarchical regression analyses partialed out M100 variance associated with age, IQ, and language ability (all P‐values <0.05). Examining the right‐hemisphere 500 Hz condition (where the largest latency differences were observed), a sensitivity of 75%, a specificity of 81%, and a positive predictive value (PPV) of 86% was obtained at a threshold of 116 msec. The M100 latency delay indicates disruption of encoding simple sensory information. Given similar findings in language impaired and nonlanguage impaired ASD subjects, a right‐hemisphere M100 latency delay appears to be an electrophysiological endophenotype for autism.
The 2022 global outbreak of Monkeypox virus (MPXV) highlighted challenges with polymerase chain reaction detection as divergent strains emerged and atypical presentations limited the applicability of ...swab sampling. Recommended testing in the United States requires a swab of lesions, which arise late in infection and may be unrecognized. We present MPXV detections using plasma microbial cell-free DNA (mcfDNA) sequencing.
Fifteen plasma samples from 12 case-patients were characterized through mcfDNA sequencing. Assay performance was confirmed through in silico inclusivity and exclusivity assessments. MPXV isolates were genotyped using mcfDNA, and phylodynamic information was imputed using publicly available sequences.
MPXV mcfDNA was detected in 12 case-patients. Mpox was not suspected in 5, with 1 having documented resolution of mpox >6 months previously. Six had moderate to severe mpox, supported by high MPXV mcfDNA concentrations; 4 died. In 7 case-patients, mcfDNA sequencing detected coinfections. Genotyping by mcfDNA sequencing identified 22 MPXV mutations at 10 genomic loci in 9 case-patients. Consistent with variation observed in the 2022 outbreak, 21 of 22 variants were G > A/C > T. Phylogenetic analyses imputed isolates to sublineages arising at different time points and from different geographic locations.
We demonstrate the potential of plasma mcfDNA sequencing to detect, quantify, and, for acute infections with high sequencing coverage, subtype MPXV using a single noninvasive test. Sequencing plasma mcfDNA may augment existing mpox testing in vulnerable patient populations or in patients with atypical symptoms or unrecognized mpox. Strain type information may supplement disease surveillance and facilitate tracking emerging pathogens.
The development of left and right superior temporal gyrus (STG) 50 ms (M50) and 100 ms (M100) auditory responses in typically developing (TD) children and in children with autism spectrum disorder ...(ASD) was examined. Reflecting differential development of primary/secondary auditory areas and supporting previous studies, it was hypothesized that whereas left and right M50 STG responses would be observed equally often in younger and older children, left and right M100 STG responses would more often be absent in younger than older children. In ASD, delayed neurodevelopment would be indicated via the observation of a greater proportion of ASD than TD subjects showing missing M100 but not M50 responses in both age groups. Missing M100 responses would be observed primarily in children with ASD with language impairment (ASD + LI) (and perhaps concomitantly lower general cognitive abilities).
Thirty-five TD controls, 63 ASD without language impairment (ASD - LI), and 38 ASD + LI were recruited. Binaural tones were presented. The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6-10 years old) and older groups (11-15 years old).
Although M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD - LI and ASD + LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD + LI (90 versus 66%, p = 0.04), with no differences between TD and ASD - LI (90 versus 76%, p = 0.14) or between ASD - LI and ASD + LI (76 versus 66%, p = 0.53). In older subjects, whereas no differences were observed between TD and ASD + LI, responses were observed more often in ASD - LI than ASD + LI. Findings were similar when splitting the ASD group into lower- and higher-cognitive functioning groups.
Although present in all groups, M50 responses were delayed in ASD. Examining the TD data, findings indicated that by 11 years, a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11 years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment.
White matter diffusion anisotropy in the acoustic radiations of the auditory pathway was characterized as a function of development in children and adolescents. Auditory-evoked neuromagnetic fields ...were also recorded from the same individuals, and the latency of the left and right superior temporal gyrus auditory response of approximately 100 ms was also obtained. White matter diffusion anisotropy increased with age. There was a commensurate shortening of the auditory-evoked response latency with increased age as well as with increased white matter diffusion anisotropy. The significant negative correlation between structural integrity of white matter pathways and electrophysiological function (response timing) of distal cortex supports a biophysical model of developmental changes in white matter myelination, conduction velocity, and cortical response timing.
16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we ...aimed to quantify the effect of 16p11.2 CNVs on brain structure.
Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.
Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen’s d > 1), the superior and middle temporal gyri (deletion < control; Cohen’s d < −1), and the caudate and hippocampus (control > duplication; −0.5 > Cohen’s d > −1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.
The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.
To identify factors contributing to a cluster of deaths from invasive group A streptococcus (GAS) infection in a nursing home facility and to prevent additional cases.
Outbreak investigation.
A ...146-bed nursing home facility in northern Nevada.
We defined a case as the isolation of GAS from a normally sterile site in a resident of nursing home A. To identify case patients, we reviewed resident records from nursing home A, the local hospital, and the hospital laboratory. We obtained oropharyngeal and skin lesion swabs from staff and residents to assess GAS colonization and performed emm typing on available isolates. To identify potential risk factors for transmission, we performed a cohort study and investigated concurrent illness among residents and surveyed staff regarding infection control practices.
Six residents met the case patient definition; 3 (50%) of them died. Among invasive GAS isolates available for analysis, 2 distinct strains were identified: emm11 (3 isolates) and emm89 (2 isolates). The rate of GAS carriage was 6% among residents and 4% among staff; carriage isolates were emm89 (8 isolates), emm11 (2 isolates), and emm1 (1 isolate). Concurrently, 35 (24%) of the residents developed a respiratory illness of unknown etiology; 41% of these persons died. Twenty-one (30%) of the surveyed employees did not always wash their hands before patient contacts, and 27 (38%) did not always wash their hands between patient contacts.
Concurrent respiratory illness likely contributed to an outbreak of invasive GAS infection from 2 strains in a highly susceptible population. This outbreak highlights the importance of appropriate infection control measures, including respiratory hygiene practices, in nursing home facilities.
In this paper, we present a learning approach to goal assignment and trajectory planning for unlabeled robots operating in 2D, obstacle-filled workspaces. More specifically, we tackle the unlabeled ...multi-robot motion planning problem with motion constraints as a multi-agent reinforcement learning problem with some sparse global reward. In contrast with previous works, which formulate an entirely new hand-crafted optimization cost or trajectory generation algorithm for a different robot dynamic model, our framework is a general approach that is applicable to arbitrary robot models. Further, by using the velocity obstacle, we devise a smooth projection that guarantees collision free trajectories for all robots with respect to their neighbors and obstacles. The efficacy of our algorithm is demonstrated through varied simulations. A video describing our method and results can be found here.
Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have ...typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen's d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions.
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