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Brusco, C.

Publications and source records attributed to Brusco, C..

2 recordsLinked to original sources

A Multimodal Framework for Understanding Perceptual Segmentation of Natural Scenes In Autism

Understanding how individuals organize complex natural scenes into perceptual segments is essential for explaining both typical and atypical sensory processing. In Autism Spectrum Disorder (ASD), differences in visual segmentation are widely documented. However, existing paradigms often rely on simplified stimuli and do not capture the dynamic, naturalistic processes underlying real world scene segmentation. To overcome those limitations, in this work we present a novel, multimodal experimental framework. The framework combines precisely timed, trial-based perceptual measurements with electroencephalography (EEG) to examine how neural activity aligns temporally with segmentation decisions, and with eye-tracking to examine visual exploration strategies and attention allocation. To demonstrate the framework, we report basic characterization results from a pilot study. Neurotypical (NT) participants and participants with ASD aged 16 years and above viewed natural scenes and textures and indicated whether two cued image regions belonged to the same or different perceptual segments. Each trial used a different pair of cues, and responses across trials enabled the estimation of subjectively perceived segmentation maps and the associated uncertainty. Both cohorts performed the task successfully and produced interpretable segmentation maps. Analysis of reaction time distributions, gaze profiles, and trial-aligned neural responses give us a window into cohort differences and the opportunity to study individual heterogeneity. Together, these findings establish a reproducible method for studying the temporal and spatial components of natural scene segmentation and illustrate that meaningful behavioral and neural distinctions in ASD may be studied with this approach. This framework provides a methodological bridge between controlled experimental stimuli and real-world perception in both neurotypical and neurodivergent populations.

neuroscience↗

Spatial patterning and immunosuppression of glioblastoma immune contexture in hypoxic niches

Glioblastoma (GBM), a highly lethal brain cancer, is notorious for its immunosuppressive microenvironment, yet current immunotherapies are ineffective. Thus, understanding the immune contexture and governing factors of immunosuppression is crucial. Here, we identified a highly dynamic temporospatial patterning of tumor-associated macrophages (TAMs) corresponding to vascular changes in GBM: as tumor vessels transition from an initial dense regular network to later scant engorged vasculature, CD68+ TAMs shift away from perivascular regions to poorly vascularized areas. Remarkably, this process is heavily influenced by the immunocompetency of host animal, as tumor vessels in immunodeficient hosts remained dense and regular while TAMs evenly distributed. Utilizing a sensitive fluorescent reporter to track tumor hypoxia, we revealed that hypoxic niche controls immunosuppression by at least two mechanisms: first, attracting and sequestering activated TAMs in hypoxic zones, and second, reprograming entrapped TAMs towards an immunotolerant state. Indeed, entrapped TAMs also experience hypoxia and upregulate phagocytic marker Cd68 and immunotolerant genes Mrc1 and Arg1, thereby facilitating debris clearing, inflammatory containment, and immunosuppression in hypoxic zones. Mechanistically, we identified Ccl8 and IL-1{beta} as two hypoxic niche factors released by TAMs in response to cues from hypoxic GBM cells, functioning to reinforce TAM retainment. Reciprocally, niche factors also shape the transcriptional responses of hypoxic tumor cells that exhibit quiescence and mesenchymal shift. Moreover, hypoxic niche factors are highly enriched in human GBMs, particularly mesenchymal subtype, and predict poor survival. Importantly, perturbing hypoxic niches resulted in reduced TAM sequestration and better tumor control. Together, understanding the mutual influence of immune contexture and metabolic landscape has important ramifications for improving efficacy of immunotherapies against GBM.

cancer biology↗