Biology subjects

DeStefano, L.

Publications and source records attributed to DeStefano, L..

3 recordsLinked to original sources

bioRxiv2025

Event-Related Spatio-Spectral Perturbation (ERSSP): A Scalp-Wide EEG Analysis Framework for Capturing Extralemniscal Thalamocortical Activity, Validated Using a Fragile X Syndrome Model

The extralemniscal thalamocortical pathway regulates large-scale modulation of cortical states but remains inaccessible to traditional EEG analysis due to its diffuse, variable, and asynchronous nature. To address this, we introduce the Event-Related Spatio-Spectral Perturbation (ERSSP) framework, which quantifies spatially distributed time-frequency responses. ERSSP summarizes the number of channels exhibiting significant spectral perturbations, capturing diffuse cortical dynamics from sensor-space EEG. We validated this approach using a passive auditory habituation task in individuals with Fragile X Syndrome (FXS), a condition marked by disrupted thalamocortical modulation. ERSSP revealed enhanced spatial extent of power increases (but not phase-locking) in FXS compared to controls. Results also showed expected gender differences, further supporting biological sensitivity of ERSSP. ERSSP provides a conceptually simple and computationally efficient method for quantifying broadly distributed sensory modulation and may enable new insights into thalamocortical function in both basic and clinical neuroscience.

neuroscience↗

bioRxiv2024

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.

neuroscience↗

bioRxiv2023

Hypersensitivity to distractors in Fragile X syndrome from loss of modulation of cortical VIP interneurons.

Attention deficit is one of the most prominent and disabling symptoms in Fragile X Syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in both humans and mice with FXS, but not their typically developing controls. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the post-stimulus period during early distractor trials in WT mice, consistent with their known role as error signals. Strikingly, however, VIP cells from Fmr1-/- mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells, could be a potential therapeutic target for attentional difficulties in FXS.

neuroscience↗