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Sharshar, T.

Publications and source records attributed to Sharshar, T..

3 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↗

An immune signature of postoperative cognitive decline in elderly patients

Postoperative cognitive decline (POCD) is the predominant complication affecting elderly patients following major surgery, yet its prediction and prevention remain challenging. Understanding biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This longitudinal study involving 26 elderly patients undergoing orthopedic surgery aimed to characterize the impact of peripheral immune cell responses to surgical trauma on POCD. Trajectory analyses of single-cell mass cytometry data highlighted early JAK/STAT signaling exacerbation and diminished MyD88 signaling post-surgery in patients who developed POCD. Further analyses integrating single-cell and plasma proteomic data collected before surgery with clinical variables yielded a sparse predictive model that accurately identified patients who would develop POCD (AUC = 0.80). The resulting POCD immune signature included one plasma protein and ten immune cell features, offering a concise list of biomarker candidates for developing point-of-care prognostic tests to personalize perioperative management of at-risk patients. The code and the data are documented and available at https://github.com/gregbellan/POCD. TeaserModeling immune cell responses and plasma proteomic data predicts postoperative cognitive decline.

neuroscience↗

Dissecting the contribution of vagal subcircuits in sepsis-induced brain dysfunctions.

Sepsis, a life-threatening syndrome caused by a dysregulated host response to infection, induces a range of acute effects on the brain, including sickness behaviour and sepsis-associated encephalopathy. In addition, sepsis can lead to durable changes in neuronal circuits, resulting in long-term impairments such as post-traumatic stress disorder (PTSD). These brain dysfunctions are not directly caused by brain infection but result from peripheral inflammatory signals relayed to the brain via neural and humoral pathways. The vagal complex in the brainstem, composed of the nucleus of the solitary tract (NTS) and the area postrema, plays a crucial role in sensing and relaying these signals. Notably, the activation of the vagal complex triggers neurovegetative, neuroendocrine, and behavioural responses to infection. Chronic electrical vagus nerve stimulation has been used clinically to treat various brain disorders and is being investigated for its potential to alleviate inflammation and immune diseases through the anti-inflammatory reflex. However, a deeper understanding of the involvement of the vagus nerve and downstream brain circuits in sepsis-induced brain activation and dysfunction is needed to optimize therapeutic strategies. To investigate the role of the vagal complex in sepsis-induced brain dysfunction, various techniques were employed to manipulate vagus nerve activity and downstream circuits in a rodent model of sepsis by caecal ligation and puncture. Subdiaphragmatic vagotomy and pharmacogenetic manipulation of NTS and nodose (i.e. vagus sensory neurons) were implemented, revealing that vagotomy effectively reduced acute brain activation, inflammatory responses, and sickness behaviour triggered by sepsis. Additionally, transient activation of NTS neurons had a significant impact on inflammatory responses, sickness behaviour, and long-term PTSD-like consequences. This study underscores the complex interplay among the vagus nerve, brain circuits, and systemic inflammation during sepsis, emphasizing the critical importance of understanding these interactions in the development of targeted therapeutic interventions.

neuroscience↗