Biology subjects

Levin, A. R.

Publications and source records attributed to Levin, A. R..

6 recordsLinked to original sources

bioRxiv2024

Longitudinal trajectories of aperiodic EEG activity in early to middle childhood

BackgroundEmerging evidence suggests that aperiodic EEG activity may follow a nonlinear growth trajectory in childhood. However, existing studies are limited by small assessment windows and cross-sectional samples that are unable to fully capture these patterns. The current study aimed to characterize the developmental trajectories of aperiodic activity longitudinally from infancy to middle childhood. We examined potential trajectory differences by sex and brain region. We further investigated whether aperiodic activity is associated with maternal anxiety symptoms, and whether these associations vary because of differential development trajectories. MethodsA community sample of children and their parents (N=391) enrolled in a longitudinal study of emotion processing were assessed at infancy, and at ages 3 years, 5 years, and 7 years. Analyses included individual growth curve and mixed effect models. Developmental trajectories of the aperiodic slope and offset were investigated across whole brain, frontal, central, temporal, and posterior regions. Associations of whole brain slope and offset with maternal anxiety symptoms were also examined. ResultsDevelopmental trajectories for both slope and offset were generally characterized by a relative increase in early childhood and a subsequent decrease or stabilization by age 7, with variation by brain region. Females showed relatively steeper slopes at some ages, and males showed relatively greater offset at certain ages. Maternal anxiety was negatively associated with slope at 3 years and positively associated with slope at 7 years. ConclusionsThe longitudinal developmental trajectory of aperiodic slope in early childhood is nonlinear and shows variation by sex and brain region. The magnitude and direction of associations with maternal anxiety varied by age, corresponding with changes in trajectories. Developmental stage should be considered when interpreting findings related to aperiodic activity in childhood.

neuroscience↗

bioRxiv2024

Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cerebral organoids

Human cerebral organoids derived from induced pluripotent stem cells can recapture early developmental processes and reveal changes involving neurodevelopmental disorders. Mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene are associated with Rett syndrome, and disease severity varies depending on the location and type of mutation. Here, we focused on neuronal activity in Rett syndrome patient-derived organoids, analyzing two types of MeCP2 mutations - a missense mutation (R306C) and a truncating mutation (V247X) - using calcium imaging with three-photon microscopy. Compared to isogenic controls, we found abnormal neuronal activity in Rett organoids and altered network function based on graph theoretic analyses, with V247X mutations impacting functional responses and connectivity more severely than R306C mutations. These changes paralleled EEG data obtained from patients with comparable mutations. Labeling DLX promoter-driven inhibitory neurons demonstrated differences in activity and functional connectivity of inhibitory and excitatory neurons in the two types of mutation. Transcriptomic analyses revealed HDAC2-associated impairment in R306C organoids and decreased GABAA receptor expression in excitatory neurons in V247X organoids. These findings demonstrate mutation-specific mechanisms of vulnerability in Rett syndrome and suggest targeted strategies for their treatment.

bioengineering↗

bioRxiv2019

Within Visit Test-Retest Reliability of EEG Profiles in Children with Autism Spectrum Disorder and Typical Development

Biomarker development is currently a high priority in neurodevelopmental disorder research. For many types of biomarkers (particularly biomarkers of diagnosis), reliability over short time periods is critically important. In the field of autism spectrum disorder (ASD), resting electroencephalography (EEG) power spectral densities (PSD) are well-studied for their potential as biomarkers. Classically, such data have been decomposed into pre-specified frequency bands (e.g., delta, theta, alpha, beta, and gamma). Recent technical advances, such as the Fitting Oscillations and One-Over-F (FOOOF) algorithm, allow for targeted characterization of the features that naturally emerge within an EEG PSD, permitting a more detailed characterization of the frequency band-agnostic shape of each individuals EEG PSD. Here, using two resting EEGs collected a median of 6 days apart from 22 children with ASD and 25 typically developing (TD) controls during the Feasibility Visit of the Autism Biomarkers Consortium for Clinical Trials, we estimate within visit test-retest reliability based on characterization of the PSD shape in two ways: (1) Using the FOOOF algorithm we estimate six parameters (offset, slope, number of peaks, and amplitude, center frequency and bandwidth of the largest alpha peak) that characterize the shape of the EEG PSD; and (2) using nonparametric functional data analyses, we decompose the shape of the EEG PSD into a reduced set of basis functions that characterize individual power spectrum shapes. We show that individuals exhibit idiosyncratic PSD signatures that are stable over recording sessions using both characterizations. Our data show that EEG activity from a brief two-minute recording provides an efficient window into understanding brain activity at the single-subject level with desirable psychometric characteristics that persist across different analytical decomposition methods. This is a necessary step towards analytical validation of biomarkers based on the EEG PSD, and provides insights into parameters of the PSD that offer short-term reliability (and thus promise as potential biomarkers of trait or diagnosis) versus those that are more variable over the short term (and thus may index state or other rapidly dynamic measures of brain function). Future research should address longer-term stability of the PSD, for purposes such as monitoring development or response to treatment.

neuroscience↗

bioRxiv2019

Developmental Changes in EEG Phase Amplitude Coupling and Phase Preference over the First Three Years After Birth

The coupling of the phase of slower electrophysiological oscillations with the amplitude of faster oscillations, termed phase-amplitude coupling (PAC), is thought to facilitate dynamic connectivity in the brain. Though the brain undergoes dramatic changes in connectivity during the first few years of life, how PAC changes through this developmental period has not been studied. Here, we examined PAC through electroencephalography (EEG) data collected longitudinally during an awake, eyes-open EEG collection paradigm in 98 children between the ages of 3 months and 3 years. We implement a novel technique developed for capturing both PAC strength and phase preference (i.e., where in the slower oscillation waveform the faster oscillation shows increased amplitude) simultaneously, and employed non-parametric clustering methods to evaluate our metrics across a range of frequency pairs and electrode locations. We found that frontal and occipital PAC, primarily between the alpha-beta and gamma frequencies, increased from early infancy to early childhood (p = 1.35 x 10-5). Additionally, we found frontal gamma coupled with the trough of the alpha-beta waveform, while occipital gamma coupled with the peak of the alpha-beta waveform. This opposing trend may reflect each regions specialization towards feedback or feedforward processing, respectively.\n\nSignificance StatementThe brain undergoes significant changes in functional connectivity during infancy and early childhood, enabling the emergence of higher-level cognition. Phase-amplitude coupling (PAC) is thought to support the functional connectivity of the brain. Here, we find PAC increases from 3 months to 3 years of age. We additionally report the frontal and occipital brain areas show opposing forms of PAC; this difference could facilitate each regions tendency towards bottom-up or top-down processing.

neuroscience↗

bioRxiv2019

Population Genomics of Nontuberculous Mycobacteria Recovered from United States Cystic Fibrosis Patients

Nontuberculous mycobacteria (NTM) pose a threat to individuals with cystic fibrosis (CF) due to an increased prevalence of pulmonary infections, innate drug resistance of the bacteria, and potential transmission between CF patients. To explore the genetic diversity of NTM isolated from CF patients within the United States (US) and to identify potential transmission events, we sequenced and analyzed the genomes of 341 NTM isolates from 191 CF patients as part of a nationwide surveillance study. The most abundant species in the isolate cohort were Mycobacterium abscessus (59.5%), followed by species in the Mycobacterium avium complex (37.5%). Phylogenomic analyses of the three M. abscessus subspecies revealed that more than half of CF patients had isolates in one of four dominant clones, including two dominant clones of M. abscessus subspecies abscessus and two dominant clones of M. abscessus subspecies massiliense. M. avium isolates from US CF patients, however, do not have dominant clones and are phylogenetically diverse. Longitudinal NTM isolates were compared to determine genome-wide single nucleotide polymorphisms (SNPs) that occur within patients over time. This information was used to compare between and within-patient SNP distributions, to quantitatively define SNP thresholds suggestive of transmission, and calculate a posterior probability of recent transmission given the SNP distance between two isolates from different patients. Out of 114 patients with M. abscessus subspecies, ten clusters of highly similar isolates from 26 patients were identified. Among the 26 patients in the M. abscessus clusters, 12 attended the same CF care centers. No highly similar isolate clusters were observed in M. avium. Our study reveals the contrasting genomic diversity and epidemiology of two major NTM taxa and the potential for between-patient exposure and cross-transmission of these emerging pathogens.

microbiology↗

bioRxiv2018

Reduced frontal gamma power at 24 months is associated with better expressive language in toddlers at risk for autism

Gamma oscillations have been associated with early language development in typically developing toddlers, and gamma band abnormalities have been observed in individuals with ASD, as well high-risk infant siblings (those having an older sibling with autism), as early as 6-months of age. The current study investigated differences in baseline frontal gamma power and its association with language development in toddlers at high versus low familial risk for autism. EEG recordings as well as cognitive and behavioral assessments were acquired at 24-months as part of prospective, longitudinal study of infant siblings of children with and without autism. Diagnosis of autism was determined at 24-36 months, and data was analyzed across three outcome groups - low risk without ASD (n=43), high-risk without ASD (n=42), and high-risk with ASD (n=16). High-risk toddlers without ASD had reduced baseline frontal gamma power (30-50Hz) compared to low-risk toddlers. Among high-risk toddlers increased frontal gamma was only marginally associated with ASD diagnosis (p=0.06), but significantly associated with reduced expressive language ability (p=0.007). No association between gamma power and language was present in the low-risk group. These findings suggest that differences in gamma oscillations in high-risk toddlers may represent compensatory mechanisms associated with improved developmental outcomes.

neuroscience↗