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Moiraghi, A.

Publications and source records attributed to Moiraghi, A..

2 recordsLinked to original sources

Human primary auditory cortex and insula encode perceptual decisions, not stimulus features

The traditional view of perceptual decision-making assumes a largely feedforward cortical hierarchy, in which sensory regions encode stimulus features that are progressively integrated with top-down signals in higher order associative areas to guide decisions. However, recent work has cast doubt on whether stimulus-and decision-related signals actually follow such a predicted spatiotemporal organization, especially in naturalistic situations where sensory cues are subtle and decisions more strongly driven by internal strategies. Leveraging the unique spatiotemporal precision of human intracerebral recordings, we map here how stimulus and decision variables are represented along the auditory cortical hierarchy as patients engage in a social voice decision task with realistic, low-salience cues. Contrary to feedforward predictions, we found no clear spatial or temporal gradient separating stimulus- and decision-related effects; rather, decision effects emerged early during stimulus exposure and, strikingly, flowed back all the way to the most primary regions of the superior temporal gyrus. In addition, the direction of these early and primary decision signals closely reflected the variability in patients specific decision criteria. Taken together, these results strongly challenge the traditional feedforward model, supporting a view in which the activity of early auditory regions does not reflect subtle stimulus categories but is instead dynamically configured by task-dependent priors and response strategies. Significant StatementThis work studies an ecological social-cognitive decision task based on subtle but natural vocal cues. Contrary to expectations, it shows that early and primary auditory activity in human intracerebral recordings does not reflect stimulus categories but instead patients decisions and decision criteria. These results are significant because they provide rare human intracerebral evidence that sensory regions are not static repositories of stimulus representations but rather dynamic, task-dependent filters that are configured by priors and decision criteria.

neuroscience↗

Nucleolin is expressed in human fetal brain development and reactivated in human glial brain tumors regulating angiogenesis and vascular metabolism

Glioblastoma (GBM) is amongst the deadliest human cancers and is characterized by high levels of vascularisation. Angiogenesis is highly dynamic during brain development and almost quiescent in the adult brain, but is reactivated in vascular-dependent CNS pathologies such as brain tumors. Nucleolin (NCL) is a known regulator of cell proliferation and angiogenesis, but its roles on physiological and pathological brain vasculature remain unknown. Here, we studied the expression of Nucleolin in the neurovascular unit (NVU) in human fetal brains and human gliomas in vivo as well as its effects on sprouting angiogenesis and endothelial metabolism in vitro. Nucleolin is highly expressed in endothelial- and perivascular cells during brain development, downregulated in the adult brain, and upregulated in glioma. Moreover, Nucleolin expression in tumor- and blood vessel cells correlated with glioma malignancy in vivo. In culture, siRNA-mediated NCL knockdown reduced human umbilical vein endothelial cell (HUVEC) sprouting angiogenesis, proliferation and filopodia extension, and reduced glucose metabolism. Mechanistically, RNA sequencing of Nucleolin knockdown in HUVECs revealed a putative p53-TIGAR-HK2 regulation of endothelial glycolysis. These findings identify Nucleolin as a neurodevelopmental factor reactivated in glioma that positively regulates sprouting angiogenesis and endothelial metabolism. Our findings have important implications in therapeutic targeting of glioma.

neuroscience↗