Biology subjects

Orsini, C.

Publications and source records attributed to Orsini, C..

4 recordsLinked to original sources

bioRxiv2025

Basal forebrain and neural correlates of self-regulation traits in sustained attention

Self-regulation is a human trait consistently associated with success in both academic and professional settings and to better mental health. Based on previous findings, we used functional imaging data in a sustained attention task to test three hypotheses on neural substrates associated with individual differences in self-regulation. The first linked higher self-regulation and cognitive control, predicting modulation of recruitment of prefrontal substrates. The second, originating in the animal literature, suggests increased recruitment of cholinergic substrates in the basal forebrain. The third predicted higher modulation of reward-sensitive regions in the brainstem in less regulated individuals for differences in reward levels during the task. The second hypothesis was confirmed by our study, which also provided suggestive evidence for the third hypothesis. Our data suggest that one mechanism of higher self-regulation in humans may ensue from greater activity in the cholinergic system to sustain attention during a cognitively simple task.

neuroscience↗

bioRxiv2024

Cognitive effort and reward. Functional imaging of time on task and the involvement of dopaminergic and cholinergic substrates

Neuroimaging studies have identified the neural substrates associated with sustained cognitive efforts and control and their modulation by rewards. Different lines of evidence implicate the prefrontal cortex (especially the anterior cingulate cortex, ACC), dopaminergic, and cholinergic substrates in this modulation. We studied here the activity of these substrates at increasing time on task (requiring increasing levels of cognitive effort) in trials within blocks with differing reward levels. In the cortex, while peaking in the ACC, activity associated with time on task was extensive, also including activity decrements outside the default mode network, primarily involving motor and somatosensory regions. Information about reward levels was carried in the ventral striatum, consistent with its motivational role, but did not reflect trade-offs with increasing efforts during time on task. Instead, the ventral tegmental area and parts of the basal forebrain (BF) corresponding to the cholinergic Ch4 nuclei increased in activity with time on task and were sensitive to reward levels. This BF activity is consistent with a cholinergic role in driving compensatory efforts modulated by reward levels. These findings identify the BF as a neuroimaging phenotype associated with sustaining task sets and cognitive efforts.

neuroscience↗

bioRxiv2024

The fMRI global signal and its association with the signal from cranial bone

The nature of the global signal, i.e. the average signal from sequential functional imaging scans of the brain or the cortex, is not well understood, but is thought to include vascular and neural components. Using resting state data, we report on the strong association between the global signal and the average signal from the part of the volume that includes the cranial bone and subdural vessels and venous collectors, separated from each other and the subdural space by multispectral segmentation procedures. While subdural vessels carried a signal with a phase delay relative to the cortex, the association with the cortical signal was strongest in the parts of the scan corresponding to the laminae of the cranial bone, reaching 80% shared variance in some individuals. These findings suggest that in resting state data vascular components may play a prominent role in the genesis of fluctuations of the global signal. Evidence from other studies on the existence of neural sources of the global signal suggests that it may reflect the action of multiple mechanisms (including cerebrovascular reactivity and autonomic control) concurrently acting to regulate global cerebral perfusion.

neuroscience↗

bioRxiv2020

A 3D human liver model of nonalcoholic steatohepatitis

AO_SCPLOWBSTRACTC_SCPLOWWe have developed an in vitro preclinical 3D Non-Alcoholic SteatoHepatitis (NASH) model by co-culturing four human primary liver cell types: hepatocytes, stellate, endothelial and Kupffer cells. Cells were embedded in a hydrogel of rat collagen in 96-well plate and a NASH-like environment was induced with a medium containing free fatty acids (FFAs) and tumor necrosis factor (TNF). This model was characterized by biochemical, imaging and transcriptomics analysis. On the one hand, we succeed in defining suitable culture conditions to maintain the 3D co-culture up to 10 days in vitro with the lowest level of steatosis, and reproducible low levels of inflammation and fibrosis. On the other hand, we induced NASH disease with a custom medium mimicking NASH features (hepatocyte injury, steatosis, inflammation and fibrosis). The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets. SO_SCPLOWUMMARYC_SCPLOWWe developed a 3D human liver model which exhibits many features of non-alcoholic steatohepatitis and that could become a platform for medium throughput drug screening.

cell biology↗