Biology subjects

Kavanaugh, B.

Publications and source records attributed to Kavanaugh, B..

3 recordsLinked to original sources

bioRxiv2025

Mutations in ASH1L cause a neurodevelopmental disorder with sex differences in epilepsy and autism

To understand brain phenotypes associated with ASH1L, we performed both studies in mouse models and clinical phenotyping of human subjects. We found in mice that ASH1L mutations result in seizures, microcephaly, and also less complex dendritic morphology. When we analyzed human subjects based for epilepsy, intellectual disability, and ASD, we found sex differences in epilepsy and autism, with epilepsy predominantly in female and ASD in male subjects. To understand the cellular and molecular mechanisms of the sex-difference, we performed whole cell patch clamp electrophysiology in mice and found hyperexcitability in female compared with male hippocampal CA1 neurons. We report the identification of sex-specific transcriptomic signatures resulting from ASH1L haploinsufficiency. Differentially expressed genes in female mice showed distinct association with epileptic encephalopathy, postnatal microcephaly and autistic behaviors. Thus, the role of ASH1L in specific circuits may be sex-dependent leading to sexual dimorphic effects from disruption of this gene.

neuroscience↗

bioRxiv2024

Dysfunctional oscillatory bursting patterns underlie working memory deficits in adolescents with ADHD

Identifying neural markers of clinical symptom fluctuations is prerequisite to developing more precise brain-targeted treatments in psychiatry. We have recently shown that working memory (WM) in healthy adults is dependent on the rise and fall interplay between alpha/beta and gamma bursts within frontoparietal regions, and that deviations in these patterns lead to WM performance errors. However, it is not known whether such bursting deviations underlie clinically relevant WM-related symptoms or clinical status in individuals with WM deficits. In adolescents (n=27) with attention deficit hyperactivity disorder (ADHD), we investigated WM-related dynamics between alpha/beta and gamma bursts in relation to clinical status fluctuations. Participants repeatedly completed a visual Sternberg spatial working memory task during EEG recording as part of their participation in two research studies (n=224 person-sessions). Source localizing EEG data to each participants structural MRI, the rate and volume of alpha, beta, and gamma bursts were examined within the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC). Alpha/beta and gamma bursts at the DLPFC and PPC displayed complimentary roles in WM processes. Alpha/beta bursting decreased during stimuli encoding and increased during the delay, while gamma bursting was elevated during encoding and decreased during the delay. Deviations in bursting patterns were associated with WM errors and clinical symptoms. We conclude that dysfunctional alpha/beta and gamma burst dynamics within the frontoparietal region underlie both intra-individual WM performance and WM symptom fluctuations in adolescents with ADHD. Such burst dynamics reflect a novel target and biomarker for WM-related treatment development.

neuroscience↗

bioRxiv2024

The association between oscillatory burst features and deviations during human working memory

Oscillatory power across multiple frequency bands has been associated with distinct working memory (WM) processes. Recent research has shown that previous observations based on averaged power are driven by the presence of transient, oscillatory burst-like events, particularly within the alpha, beta, and gamma bands. However, the interplay between different burst events in human WM is not well understood. The current EEG study aimed to investigate the dynamics between alpha (8-12 Hz)/beta (15-29 Hz) and high frequency activity (HFA; 55-80 Hz) bursts in human WM, particularly burst features and error-related deviations during the encoding and maintenance of WM in healthy adults. Oscillatory burst features within the alpha, beta and HFA bands were examined at frontal and parietal electrodes in healthy young adults during a Sternberg working memory task. Averaged power dynamics were driven by oscillatory burst features, most consistently the burst rate and burst power. Alpha/beta and HFA bursts displayed complementary roles in WM processes, in that alpha and beta bursting decreased during encoding and increased during delay, while HFA bursting had the opposite pattern, i.e., increased during encoding and decreased during the delay. Critically, weaker variation in burst dynamics across stages was associated with incorrect responses and impaired overall task performance. Together, these results indicate that successful human WM is dependent on the rise and fall interplay between alpha/beta and HFA bursts, with such burst dynamics reflecting a novel target for the development of treatment in clinical populations with WM deficits.

neuroscience↗