Biology subjects

Kelley, N.

Publications and source records attributed to Kelley, N..

3 recordsLinked to original sources

bioRxiv2023

Test-retest reliability of spectral parameterization by 1/f characterization using SpecParam

SpecParam (formally known as FOOOF) allows for the refined measurements of electroencephalography periodic and aperiodic activity, and potentially provides a non-invasive measurement of excitation:inhibition balance. However, little is known about the psychometric properties of this technique. This is integral for understanding the usefulness of SpecParam as a tool to determine differences in measurements of cognitive function, and electroencephalography activity. We used intraclass correlation coefficients (ICC) to examine the test-retest reliability of parameterized activity across three sessions (90 minutes apart and 30 days later) in 49 healthy young adults at rest with eyes open (EO), eyes closed (EC), and during three EC cognitive tasks including subtraction (Math), music recall (Music), and episodic memory (Memory). ICCs were good for the aperiodic exponent and offset (ICCs > .70) and parameterized periodic activity (ICCs > .66 for alpha and beta power, central frequency, and bandwidth) across conditions. Across all three sessions, SpecParam performed poorly in EO (40% of participants had poor fits over non-central sites) and had poor test-retest reliability for parameterized periodic activity. SpecParam mostly provides reliable metrics of individual differences in parameterized neural activity. More work is needed to understand the suitability of EO resting data for parameterization using SpecParam.

neuroscience↗

bioRxiv2023

Medication-Invariant Resting Aperiodic and Periodic Neural Activity in Parkinson's Disease

Parkinsons Disease (PD) has been associated with greater total power in canonical frequency bands (i.e., alpha, beta) of the resting electroencephalogram (EEG). However, PD has also been associated with a reduction in the proportion of total power across all frequency bands. This discrepancy may be explained by aperiodic activity (exponent and offset) present across all frequency bands. Here, we examined differences in the eyes-open and eyes-closed resting EEG of PD participants (N = 26) on and off medication, and age-matched controls (CTL; N = 26). We extracted power from canonical frequency bands using traditional methods (total alpha and beta power) and extracted separate parameters for periodic (parameterized alpha and beta power) and aperiodic activity (exponent and offset). Cluster-based permutation tests over spatial and frequency dimensions indicated that total alpha and beta power, and aperiodic exponent and offset were greater in PD participants, independent of medication status. After removing the exponent and offset, greater alpha power in PD (vs. CTL) was only present in eyes-open recordings and no reliable differences in beta power were observed. Differences between PD and CTLs in the resting EEG are likely driven by aperiodic activity, suggestive of greater relative inhibitory neural activity and greater neuronal spiking. Our findings suggest that resting EEG activity in PD is characterized by medication-invariant differences in aperiodic activity which is independent of the increase in alpha power with EO. This highlights the importance of considering aperiodic activity contributions to the neural correlates of brain disorders.

neuroscience↗

bioRxiv2022

The leucine-rich repeat (LRR) domain of NLRP3 is required for NLRP3 inflammasome activation in macrophages

The NLRP3 inflammasome is a critical component of innate immunity that defends the host from microbial infections. However, its aberrant activation contributes to the pathogenesis of several inflammatory diseases. Activation of the NLRP3 inflammasome induces the secretion of proinflammatory cytokines IL-1{beta} and IL-18, and pyroptotic cell death. NLRP3 contains a leucine-rich repeat (LRR) domain at its C-terminus. Although posttranslational modifications in this LRR domain have been shown to regulate NLRP3 inflammasome activation, the role of the entire LRR domain in NLRP3 inflammasome activation remains controversial. Here, we generated mouse macrophages that express an endogenous NLRP3 mutant lacking the LRR domain. Deletion of the LRR domain destabilized endogenous NLRP3 protein and abolished NLRP3 inflammasome activation in macrophages. Furthermore, using NLRP3-deficient macrophages that are reconstituted with NLRP3 mutants lacking the LRR domain, we found that deletion of the LRR domain inhibited NLRP3 inflammasome activation. Mechanistically, deletion of the LRR domain abolished NLRP3 self-association, oligomerization, and interaction with the essential regulator NEK7. Our results demonstrate a critical role for the LRR domain in NLRP3 inflammasome activation.

immunology↗