Estimating the Period Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During the Omicron (BA.1) Surge in New York City (NYC), 1 January to 16 March 2022.

In a population-based survey of adults in New York City, we assessed positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests (including via exclusive at-home testing) and possible cases among untested respondents. An estimated 27.4% (95% confidence interval [CI]: 22.8%-32.0%) or 1.8 million adults (95% CI: 1.6-2.1 million) had SARS-CoV-2 infection between 1 January and 16 March 2022.

The Epidemiology of Long Coronavirus Disease in US Adults.

BACKGROUND: We estimated the prevalence of long COVID and impact on daily living among a representative sample of adults in the United States. METHODS: We conducted a population-representative survey, 30 June-2 July 2022, of a random sample of 3042 US adults aged 18 years or older and weighted to the 2020 US population. Using questions developed by the UK's Office of National Statistics, we estimated the prevalence of long COVID, by sociodemographics, adjusting for gender and age. RESULTS: An estimated 7.3% (95% confidence interval: 6.1-8.5%) of all respondents reported long COVID, corresponding to approximately 18 828 696 adults. One-quarter (25.3% [18.2-32.4%]) of respondents with long COVID reported their day-to-day activities were impacted "a lot" and 28.9% had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection more than 12 months ago. The prevalence of long COVID was higher among respondents who were female (adjusted prevalence ratio [aPR]: 1.84 [1.40-2.42]), had comorbidities (aPR: 1.55 [1.19-2.00]), or were not (vs were) boosted (aPR: 1.67 [1.19-2.34]) or not vaccinated (vs boosted) (aPR: 1.41 [1.05-1.91]). CONCLUSIONS: We observed a high burden of long COVID, substantial variability in prevalence of SARS-CoV-2, and risk factors unique from SARS-CoV-2 risk, suggesting areas for future research. Population-based surveys are an important surveillance tool and supplement to ongoing efforts to monitor long COVID.

The prevalence of SARS-CoV-2 infection and long COVID in U.S. adults during the BA.4/BA.5 surge, June-July 2022.

Due to changes in SARS-CoV-2 testing practices, passive case-based surveillance may be an increasingly unreliable indicator for monitoring the burden of SARS-CoV-2, especially during surges. We conducted a cross-sectional survey of a population-representative sample of 3042 U.S. adults between June 30 and July 2, 2022, during the Omicron BA.4/BA.5 surge. Respondents were asked about SARS-CoV-2 testing and outcomes, COVID-like symptoms, contact with cases, and experience with prolonged COVID-19 symptoms following prior infection. We estimated the weighted age and sex-standardized SARS-CoV-2 prevalence, during the 14-day period preceding the interview. We estimated age and gender adjusted prevalence ratios (aPR) for current SARS-CoV-2 infection using a log-binomial regression model. An estimated 17.3% (95% CI 14.9, 19.8) of respondents had SARS-CoV-2 infection during the two-week study period-equating to 44 million cases as compared to 1.8 million per the CDC during the same time period. SARS-CoV-2 prevalence was higher among those 18-24 years old (aPR 2.2, 95% CI 1.8, 2.7) and among non-Hispanic Black (aPR 1.7, 95% CI 1.4,2.2) and Hispanic adults (aPR 2.4, 95% CI 2.0, 2.9). SARS-CoV-2 prevalence was also higher among those with lower income (aPR 1.9, 95% CI 1.5, 2.3), lower education (aPR 3.7 95% CI 3.0,4.7), and those with comorbidities (aPR 1.6, 95% CI 1.4, 2.0). An estimated 21.5% (95% CI 18.2, 24.7) of respondents with a SARS-CoV-2 infection >4 weeks prior reported long COVID symptoms. The inequitable distribution of SARS-CoV-2 prevalence during the BA.4/BA.5 surge will likely drive inequities in the future burden of long COVID.

Self-Reported Use of HIV Preexposure Prophylaxis Is Highly Accurate Among Sexual Health Clinic Patients in New York City.

ABSTRACT: In New York City, 91% of sexually transmitted infection clinic patients reported preexposure prophylaxis (PrEP) use that matched the detection of PrEP in their serum. Self-report had 80% sensitivity and 96% specificity ( κ = 0.79) compared with measured PrEP. Our findings suggest that self-report may be a valid indicator of PrEP uptake.

Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

La formulation de définitions précises de cas cliniques fait partie intégrante d'un processus efficace de surveillance de la santé publique. Alors que ces définitions devraient, dans l'idéal, s'appuyer sur un ensemble standardisé et fixe de critères de définition, elles nécessitent souvent une révision pour tenir compte des nouvelles connaissances relatives à la maladie concernée et des améliorations apportées aux tests diagnostiques. Pour être optimales, les définitions de cas doivent aussi établir un équilibre entre sensibilité et spécificité qui reflète leur utilisation aux fins prévues. À la suite de la pandémie de grippe H1N1 de 2009-2010, l'Organisation mondiale de la Santé (OMS) a lancé une consultation technique sur la surveillance mondiale de la grippe. Cela a conduit à des améliorations concernant la sensibilité et la spécificité de la définition de cas pour la grippe ­ c'est-à-dire une maladie respiratoire dont seule la symptomatologie reste à définir. Le processus de révision n'a pas seulement modifié la définition du syndrome de type grippal pour inclure une liste simplifiée des critères le mieux à même de prédire une infection grippale, il a également permis de clarifier le langage utilisé dans la définition pour en améliorer l'interprétation. Par ailleurs, afin de tenir compte des cas sévères de grippe qui nécessitaient une hospitalisation, une nouvelle définition de cas a été introduite concernant l'infection aigüe sévère des voies respiratoires dans tous les groupes d'âge. Il a été constaté que les nouvelles définitions reflétaient davantage de cas, sans pour autant compromettre la spécificité. S'il est vrai que la distinction clinique de la grippe des autres infections respiratoires continue de poser problème, l'utilisation mondiale des nouvelles définitions de cas de l'OMS devrait permettre de dégager des tendances mondiales concernant les caractéristiques et la transmission des virus grippaux ainsi que la charge de morbidité qui leur est associée.

La elaboración de definiciones precisas de los casos clínicos es una parte fundamental de un proceso efectivo de la vigilancia de la salud pública. Aunque tales definiciones deberían, idealmente, estar basadas en una recopilación estandarizada y fija de criterios de definición, a menudo necesitan una revisión para reflejar el nuevo conocimiento de la enfermedad existente y las mejoras en las pruebas de diagnóstico. Las definiciones óptimas de los casos también deben tener un equilibrio entre sensibilidad y especificidad que refleje su uso previsto. Después de la pandemia de gripe H1N1 en 2009-2010, la Organización Mundial de la Salud (OMS) inició una consulta técnica para la vigilancia mundial de la gripe. Esto dio lugar a mejoras en la sensibilidad y la especificidad de las definiciones de los casos de gripe, es decir, una enfermedad respiratoria que carece de una sintomatología definitoria singular. El proceso de revisión no solo modificó la definición de las enfermedades similares a la gripe para incluir una lista simplificada de los criterios que demostraron ser más predictivos de la infección por gripe, sino que también aclaró el lenguaje utilizado para la definición, con el fin de mejorar su interpretación. Para englobar los casos graves de gripe que requirieron hospitalización, también se desarrolló una nueva definición de los casos de la infección respiratoria aguda grave en todos los grupos de edad. Se ha descubierto que las nuevas definiciones engloban más casos sin comprometer la especificidad. A pesar del desafío que todavía plantea la separación clínica de la gripe de otras infecciones respiratorias, el uso global de las nuevas definiciones de los casos de la OMS debería ayudar a determinar las tendencias mundiales en las características y transmisión de los virus de la gripe y la carga de la enfermedad asociada.

Auditory Evoked M100 Response Latency is Delayed in Children with 16p11.2 Deletion but not 16p11.2 Duplication.

Individuals with the 16p11.2 BP4-BP5 copy number variant (CNV) exhibit a range of behavioral phenotypes that may include mild impairment in cognition and clinical diagnoses of autism spectrum disorder (ASD). To better understand auditory processing impairments in populations with this chromosomal variation, auditory evoked responses were examined in children with the 16p11.2 deletion, 16p11.2 duplication, and age-matched controls. Stimuli consisted of sinusoidal binaural tones presented passively while children underwent recording with magnetoencephalography (MEG). The primary indicator of auditory processing impairment was the latency of the ∼100-ms "M100" auditory response detected by MEG, with the 16p11.2 deletion population exhibiting profoundly delayed M100 latencies relative to controls. This delay remained even after controlling for potential confounds such as age and cognitive ability. No significant difference in M100 latency was observed between 16p11.2 duplication carriers and controls. Additionally, children meeting diagnostic criteria for ASD (16p11.2 deletion carriers) exhibited nonsignificant latency delays when compared with the corresponding CNV carriers not meeting criteria for ASD. Present results indicate that 16p11.2 deletion is associated with auditory processing delays analogous to (but substantially more pronounced than) those previously reported in "idiopathic" ASD.

Oral COVID-19 Antiviral Uptake Among a Highly Vaccinated US Cohort of Adults With SARS-CoV-2 Infection Between December 2021 and October 2022.

Background: We described the oral nirmatrelvir/ritonavir (NMV/r) and molnupiravir (MOV) uptake among a subgroup of highly vaccinated adults in a US national prospective cohort who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 12/2021 and 10/2022. Methods: We estimate antiviral uptake within 5 days of SARS-CoV-2 infection, as well as age- and gender-adjusted antiviral uptake prevalence ratios by antiviral eligibility (based on age and comorbidities), sociodemographic characteristics, and clinical characteristics including vaccination status and history of long coronavirus disease 2019 (COVID). Results: NMV/r uptake was 13.6% (95% CI, 11.9%-15.2%) among 1594 participants, and MOV uptake was 1.4% (95% CI, 0.8%-2.1%) among 1398 participants. NMV/r uptake increased over time (1.9%; 95% CI, 1.0%-2.9%; between 12/2021 and 3/2022; 16.5%; 95% CI, 13.0%-20.0%; between 4/2022 and 7/2022; and 25.3%; 95% CI, 21.6%-29.0%; between 8/2022 and 10/2022). Participants age ≥65 and those who had comorbidities for severe COVID-19 had higher NMV/r uptake. There was lower NMV/r uptake among non-Hispanic Black participants (7.2%; 95% CI, 2.4%-12.0%; relative to other racial/ethnic groups) and among individuals in the lowest income groups (10.6%; 95% CI, 7.3%-13.8%; relative to higher income groups). Among a subset of 278 participants with SARS-CoV-2 infection after 12/2021 who also had a history of prior SARS-CoV-2 infection, those with (vs without) a history of long COVID reported greater NMV/r uptake (22.0% vs 7.9%; P = .001). Among those prescribed NMV/r (n = 216), 137 (63%; 95% CI, 57%-70%) reported that NMV/r was helpful for reducing COVID-19 symptoms. Conclusions: Despite proven effectiveness against severe outcomes, COVID-19 antiviral uptake remains low among those with SARS-CoV-2 infection in the United States. Further outreach to providers and patients to improve awareness of COVID-19 oral antivirals and indications is needed.

The prevalence of SARS-CoV-2 infection and other public health outcomes during the BA.2/BA.2.12.1 surge, New York City, April-May 2022.

BACKGROUND: Routine case surveillance data for SARS-CoV-2 are incomplete, unrepresentative, missing key variables of interest, and may be increasingly unreliable for timely surge detection and understanding the true burden of infection. METHODS: We conducted a cross-sectional survey of a representative sample of 1030 New York City (NYC) adult residents ≥18 years on May 7-8, 2022. We estimated the prevalence of SARS-CoV-2 infection during the preceding 14-day period. Respondents were asked about SARS-CoV-2 testing, testing outcomes, COVID-like symptoms, and contact with SARS-CoV-2 cases. SARS-CoV-2 prevalence estimates were age- and sex-adjusted to the 2020 U.S. POPULATION: We triangulated survey-based prevalence estimates with contemporaneous official SARS-CoV-2 counts of cases, hospitalizations, and deaths, as well as SARS-CoV-2 wastewater concentrations. RESULTS: We show that 22.1% (95% CI 17.9-26.2%) of respondents had SARS-CoV-2 infection during the two-week study period, corresponding to ~1.5 million adults (95% CI 1.3-1.8 million). The official SARS-CoV-2 case count during the study period is 51,218. Prevalence is estimated at 36.6% (95% CI 28.3-45.8%) among individuals with co-morbidities, 13.7% (95% CI 10.4-17.9%) among those 65+ years, and 15.3% (95% CI 9.6-23.5%) among unvaccinated persons. Among individuals with a SARS-CoV-2 infection, hybrid immunity (history of both vaccination and infection) is 66.2% (95% CI 55.7-76.7%), 44.1% (95% CI 33.0-55.1%) were aware of the antiviral nirmatrelvir/ritonavir, and 15.1% (95% CI 7.1-23.1%) reported receiving it. Hospitalizations, deaths and SARS-CoV-2 virus concentrations in wastewater remained well below that during the BA.1 surge. CONCLUSIONS: Our findings suggest that the true magnitude of NYC's BA.2/BA.2.12.1 surge may have been vastly underestimated by routine case counts and wastewater surveillance. Hybrid immunity, bolstered by the recent BA.1 surge, likely limited the severity of the BA.2/BA.2.12.1 surge.

It is difficult to assess the true prevalence of SARS-CoV-2, the virus that causes COVID-19, due to changes in testing practices and behaviors, including increasing at-home testing and decreasing healthcare provider-based testing. We conducted a population-representative survey in New York City to estimate the prevalence of SARS-CoV-2 during the second Omicron surge in spring 2022. We compared survey-based SARS-CoV-2 prevalence estimates with data on diagnosed cases, hospitalizations, deaths, and SARS-CoV-2 concentration in wastewater. Our survey-based estimates were nearly 30 times higher than official case counts and estimates of immunity among those with active infection were high. Taken together, our results suggest that the magnitude of the second Omicron surge was likely significantly underestimated, and high levels of immunity likely prevented a major surge in hospitalizations/deaths. Our findings might inform future work on COVID-19 surveillance and how to mitigate its spread.

Brief Report: Use of Remnant Specimens to Assess Use of HIV PrEP Among Populations With Risk of HIV Infection: A Novel Approach.

BACKGROUND: HIV-uninfected persons being evaluated for sexually transmitted infections (STIs) may be good HIV pre-exposure prophylaxis (PrEP) candidates. We measured PrEP use in a sentinel STI patient population. DESIGN: Cross-sectional study, New York City Sexual Health Clinics (January 2019-June 2019). METHODS: Remnant serum samples from 644 HIV-uninfected men who have sex with men (MSM) and 97 women diagnosed with chlamydia, gonorrhea, and/or early syphilis were assayed for tenofovir and emtricitabine levels using a validated liquid chromatography-mass spectrometry assay. Using paired test results and medical records, we assessed (1) prevalence and (2) correlates of PrEP use on the day of STI diagnosis (adjusted prevalence ratios [aPRs]). RESULTS: PrEP use among 741 patients was 32.7% [95% confidence interval (CI): 29.3 to 36.0]; 37.3% for MSM and 2.1% for women. PrEP use was high among White MSM (46.8%) and lowest among women. Among MSM with rectal chlamydia/gonorrhea or early syphilis, PrEP use was associated with age [aPR = 1.7 (95% CI: 1.2 to 2.4) for ages 25-34 years and aPR = 2.0 (1.4 to 2.9) for ages 35-44 years, vs. 15 to 24 years]; number of recent sex partners [aPR = 1.4 (1.0 to 2.0) for 3-5 partners, aPR = 2.1 (1.5 to 3.0) for 6-10 partners, aPR = 2.2 (1.6 to 3.1) for >10 partners, vs. ≤2 partners]; having sex/needle-sharing partners with HIV [aPR = 1.4 (1.1-1.7)]; and inconsistent condom use [aPR = 3.3 (1.8-6.1)]. Race/ethnicity, past-year STI diagnosis, and postexposure prophylaxis use were not associated. CONCLUSIONS: One in 3 people with newly diagnosed STIs had detectable serum PrEP, and PrEP use was exceedingly rare among women. Routinely collected remnant samples can be used to measure PrEP use in populations at high risk of HIV acquisition.

The Importance of Incorporating At-Home Testing Into SARS-CoV-2 Point Prevalence Estimates: Findings From a US National Cohort, February 2022.

BACKGROUND: Passive, case-based surveillance underestimates the true extent of active infections in the population due to undiagnosed and untested cases, the exclusion of probable cases diagnosed point-of-care rapid antigen tests, and the exclusive use of at-home rapid tests which are not reported as part of case-based surveillance. The extent in which COVID-19 surveillance may be underestimating the burden of infection is likely due to time-varying factors such as decreased test-seeking behaviors and increased access to and availability of at-home testing. OBJECTIVE: The objective of this study is to estimate the prevalence of SARS-CoV-2 based on different definitions of a case to ascertain the extent to which cases of SARS-CoV-2 may be underestimated by case-based surveillance. METHODS: A survey on COVID-19 exposure, infection, and testing was administered to calculate point prevalence of SARS-CoV-2 among a diverse sample of cohort adults from February 8, 2022, to February 22, 2022. Three-point prevalence estimates were calculated among the cohort, as follows: (1) proportion positives based on polymerase chain reaction (PCR) and rapid antigen tests; (2) proportion positives based on testing exclusively with rapid at-home tests; and (3) proportion of probable undiagnosed cases. Test positivity and prevalence differences across booster status were also examined. RESULTS: Among a cohort of 4328, there were a total of 644 (14.9%) cases. The point prevalence estimate based on PCR or rapid antigen tests was 5.5% (95% CI 4.8%-6.2%), 3.7% (95% CI 3.1%-4.2%) based on at-home rapid tests, and 5.7% (95% CI 5.0%-6.4%) based on the case definition of a probable case. The total point prevalence across all definitions was 14.9% (95% CI 13.8%-16.0%). The percent positivity among PCR or rapid tests was 50.2%. No statistically significant differences were observed in prevalence between participants with a COVID-19 booster compared to fully vaccinated and nonboosted participants except among exclusive at-home rapid testers. CONCLUSIONS: Our findings suggest a substantial number of cases were missed by case-based surveillance systems during the Omicron B.1.1.529 surge, when at-home testing was common. Point prevalence surveys may be a rapid tool to be used to understand SARS-CoV-2 prevalence and would be especially important during case surges to measure the scope and spread of active infections in the population.

Household factors and the risk of severe COVID-like illness early in the U.S. pandemic.

OBJECTIVE: To investigate the role of children in the home and household crowding as risk factors for severe COVID-19 disease. METHODS: We used interview data from 6,831 U.S. adults screened for the Communities, Households and SARS/CoV-2 Epidemiology (CHASING) COVID Cohort Study in April 2020. RESULTS: In logistic regression models, the adjusted odds ratio [aOR] of hospitalization due to COVID-19 for having (versus not having) children in the home was 10.5 (95% CI:5.7-19.1) among study participants living in multi-unit dwellings and 2.2 (95% CI:1.2-6.5) among those living in single unit dwellings. Among participants living in multi-unit dwellings, the aOR for COVID-19 hospitalization among participants with more than 4 persons in their household (versus 1 person) was 2.5 (95% CI:1.0-6.1), and 0.8 (95% CI:0.15-4.1) among those living in single unit dwellings. CONCLUSION: Early in the US SARS-CoV-2 pandemic, certain household exposures likely increased the risk of both SARS-CoV-2 acquisition and the risk of severe COVID-19 disease.

Household factors and the risk of severe COVID-like illness early in the US pandemic.

OBJECTIVE: To investigate the role of children in the home and household crowding as risk factors for severe COVID-19 disease. METHODS: We used interview data from 6,831 U.S. adults screened for the Communities, Households and SARS/CoV-2 Epidemiology (CHASING) COVID Cohort Study in April 2020. RESULTS: In logistic regression models, the adjusted odds ratio [aOR] of hospitalization due to COVID-19 for having (versus not having) children in the home was 10.5 (95% CI:5.7-19.1) among study participants living in multi-unit dwellings and 2.2 (95% CI:1.2-6.5) among those living in single unit dwellings. Among participants living in multi-unit dwellings, the aOR for COVID-19 hospitalization among participants with more than 4 persons in their household (versus 1 person) was 2.5 (95% CI:1.0-6.1), and 0.8 (95% CI:0.15-4.1) among those living in single unit dwellings. CONCLUSION: Early in the US SARS-CoV-2 pandemic, certain household exposures likely increased the risk of both SARS-CoV-2 acquisition and the risk of severe COVID-19 disease.

Haiti's rural Central Plateau: Baseline data from mobile health clinics.

INTRODUCTION: George Washington Students for Haiti conducts mobile clinics in the Central Plateau of Haiti. Baseline health data for specific rural areas of Haiti are needed. METHODS: Medical teams conducted mobile clinics in rural locations of Haiti's Central Plateau. Diagnoses, blood pressure, growth parameters, medications prescribed, and referrals were recorded. RESULTS: Analyses included 865 patients. The leading pediatric diagnoses were acute respiratory infection, dermatitis, and abdominal pain. Using height for age, 22.9% of children were categorized as malnourished. The primary adult diagnoses were gastroesophageal reflux disease (GERD) (23.3%), genitourinary disorders (15.9%), and cataracts (15.1%). Of all adults, 21.3% had hypertension Stage 1, and 15.4% had hypertension Stage 2. DISCUSSION: This study provides valuable baseline health data for those providing medical care in the Central Plateau of Haiti. Effective health care targets include intestinal parasitic infections and malnourishment for children; hypertension and GERD for adults.

Digital Gaming to Improve Adherence Among Adolescents and Young Adults Living With HIV: Mixed-Methods Study to Test Feasibility and Acceptability.

BACKGROUND: An estimated 50% of adolescents and young adults (AYA) living with HIV are failing to adhere to prescribed antiretroviral treatment (ART). Digital games are effective in chronic disease management; however, research on gaming to improve ART adherence among AYA is limited. OBJECTIVE: We assessed the feasibility and acceptability of video gaming to improve AYA ART adherence. METHODS: Focus group discussions and surveys were administered to health care providers and AYA aged 13 to 24 years living with HIV at a pediatric HIV program in Washington, DC. During focus group discussions, AYA viewed demonstrations of 3 game prototypes linked to portable Wisepill medication dispensers. Content analysis strategies and thematic coding were used to identify adherence themes and gaming acceptance and feasibility. Likert scale and descriptive statistics were used to summarize response frequencies. RESULTS: Providers (n=10) identified common adherence barriers and strategies, including use of gaming analogies to improve AYA ART adherence. Providers supported exploration of digital gaming as an adherence intervention. In 6 focus group discussions, 12 AYA participants identified disclosure of HIV status and irregular daily schedules as major barriers to ART and use of alarms and pillboxes as reminders. Most AYA were very or somewhat likely to use the demonstrated game prototypes to help with ART adherence and desired challenging, individually tailored, user-friendly games with in-game incentives. Game prototypes were modified accordingly. CONCLUSIONS: AYA and their providers supported the use of digital games for ART adherence support. Individualization and in-game incentives were preferable and informed the design of an interactive technology-based adherence intervention among AYA living with HIV.

Resting-state alpha in autism spectrum disorder and alpha associations with thalamic volume.

Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha rhythms, associations between thalamic structure and alpha activity were examined. RS magnetoencephalography was obtained from 47 typically-developing children (TDC) and 41 children with ASD. RS alpha activity was measured using distributed source localization. Left and right thalamic volume measurements were also obtained. In both groups, the strongest alpha activity was observed in Calcarine Sulcus regions. In Calcarine regions, only TDC showed the expected association between age and alpha peak frequency. ASD had more alpha activity than TDC in regions bordering the Central Sulcus as well as parietal association cortices. In ASD, whereas greater left Central Sulcus relative alpha activity was associated with higher Social Responsiveness Scale (SRS) scores, greater Calcarine region relative alpha activity was associated with lower SRS scores. Although thalamic volume group differences were not observed, relationships between thalamic volume and Calcarine alpha power were unique to TDC. The present study also identified a failure to shift peak alpha frequency as a function of age in primary alpha-generating areas in children with ASD. Findings suggested that increased RS alpha activity in primary motor and somatosensory as well as parietal multimodal areas-with increased alpha thought to reflect greater inhibition-might impair the ability to identify or interpret social cues. Finally, to our knowledge, this is the first study to report associations between thalamic volume and alpha power, an association observed only in TDC. The lack of thalamic and alpha associations in ASD suggests thalamic contributions to RS alpha abnormalities in ASD.

Neuromagnetic oscillations predict evoked-response latency delays and core language deficits in autism spectrum disorders.

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.

Missing and delayed auditory responses in young and older children with autism spectrum disorders.

BACKGROUND: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Maturational differences in thalamocortical white matter microstructure and auditory evoked response latencies in autism spectrum disorders.

White matter diffusion anisotropy in the acoustic radiations was characterized as a function of development in autistic and typically developing children. Auditory-evoked neuromagnetic fields were also recorded from the same individuals and the latency of the left and right middle latency superior temporal gyrus auditory ~50ms response (M50)(1) was measured. Group differences in structural and functional auditory measures were examined, as were group differences in associations between white matter pathways, M50 latency, and age. Acoustic radiation white matter fractional anisotropy did not differ between groups. Individuals with autism displayed a significant M50 latency delay. Only in typically developing controls, white matter fractional anisotropy increased with age and increased white matter anisotropy was associated with earlier M50 responses. M50 latency, however, decreased with age in both groups. Present findings thus indicate that although there is loss of a relationship between white matter structure and auditory cortex function in autism spectrum disorders, and although there are delayed auditory responses in individuals with autism than compared with age-matched controls, M50 latency nevertheless decreases as a function of age in autism, parallel to the observation in typically developing controls (although with an overall latency delay). To understand auditory latency delays in autism and changes in auditory responses as a function of age in controls and autism, studies examining white matter as well as other factors that influence auditory latency, such as synaptic transmission, are of interest.

Delayed magnetic mismatch negativity field, but not auditory M100 response, in specific language impairment.

Recent studies show that electrophysiological markers of auditory processing such as the cortical 100 ms response (M100) and the mismatch field, derived from magnetoencephalography, might be used to identify children with autism spectrum disorders--M100 peak latency--and to stratify children with autism according to the degree of language impairment--mismatch field peak latency. The present study examined the latency of right superior temporal gyrus M100 and mismatch field in a cohort of children and young adolescents with specific language impairment (n=17), in comparison with age-matched and nonverbal intelligence quotient-matched typically developing controls (n=21). Neither group showed symptoms associated with autism. Although M100 latency (reflecting early auditory processing) did not distinguish controls from children with specific language impairment, the later 'change detection' mismatch field response was significantly delayed (by >50 ms) in the specific language impairment group. Linear discriminant analysis confirmed the role of mismatch field latency (92%) but not M100 latency (8%) in distinguishing groups. The present results lend support to the claim that a delayed M100 is specific to autism spectrum disorders (with relative independence of degree of language impairment) and that a delayed mismatch field reflects an abnormality more generally associated with language impairment, suggesting that mismatch field delay in the present specific language impairment group and previously reported in autistic children with language impairment may be indicative of a common neural system dysfunction.