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Passarini, L.

Publications and source records attributed to Passarini, L..

2 recordsLinked to original sources

Susceptibility to multitasking in chronic stroke is associated to damage of the multiple demand system and leads to lateralized visuospatial deficits

Functional impairment after stroke is related to the amount of brain damage but there is no strict correspondence between lesion and magnitude of the deficit or its recovery. Theoretical constructs such as cognitive or brain reserve have been invoked as unspecific protective factors to explain this mismatch. Here, we consider the opposite point of view, that is the instances in which this protection is lost or overturned. Several studies have shown - in domains encompassing sensory, motor, and cognitive deficits - that paradigms in which the inherent processing limits of the brain are stressed (e.g., by introducing multitasking and attentional load), are indeed capable to unveil the presence of deficits that are otherwise missed. We administered a computerized multitasking paradigm to a sample of 46 consecutive patients with first-ever unilateral subacute to chronic stroke and no sign of lateralized spatial-attentional disorders according to established diagnostic tests. We then used cluster analysis to classify patients, in a purely data-driven manner, according to their multivariate pattern of performance across different conditions (e.g., single- vs dual-tasking, ipsi- vs. contra-lesional stimuli). This enabled us to identify, within a group of putatively spared patients, a cluster of individuals presenting with stark contralesional biases of spatial awareness exclusively in conditions of concurrent attentional load, i.e. a phenotype characterised by high susceptibility to multitasking. This construct was also captured by a latent factor obtained from principal component analysis, providing a continuous susceptibility index across the whole sample. In spite of similar lesion volume, patients in the high susceptibility cluster presented worse performance in activities of daily living and neuropsychological tests evaluating domain-general abilities spanning attention, executive functions, and reasoning. Multivariate predictive modeling based on lesions location and structural disconnections revealed distinctive correlates of high sensitivity to multitasking in the Multiple-Demand (MD) System, a network of frontal and fronto-parietal areas subserving domain general processes. Damage in these areas may critically interact with domain-specific ones (e.g., devoted to spatial attention), resulting in subtle, but significant difficulties for patients in everyday life situations. In conclusion, the construct of susceptibility to multitasking has the promising potential to provide us a better understanding of what marks the passage, after brain damage, to clinically visible deficits. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/561866v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@a1bc89org.highwire.dtl.DTLVardef@60cfedorg.highwire.dtl.DTLVardef@1f2ed85org.highwire.dtl.DTLVardef@1c7e5ec_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Simultaneous targeting of AMPK and mTOR is a novel therapeutic strategy against prostate cancer

Metastatic colonization by circulating cancer cells is a highly inefficient process. To colonize distant organs, disseminating cancer cells must overcome many obstacles in foreign microenvironments, and only a small fraction of them survives this process. How these disseminating cancer cells cope with stress and initiate metastatic process is not fully understood. In this study, we report that the metastatic onset of prostate cancer cells is associated with the dynamic conversion of metabolism signaling pathways governed by the energy sensors AMPK and mTOR. While in circulation in blood flow, the disseminating cancer cells display decreased mTOR and increased AMPK activities that protect them from stress-induced death. However, after metastatic onset, the mTOR-AMPK activities are reversed, enabling mTOR-dependent tumor growth. Suppression of this dynamic conversion by co-targeting of AMPK and mTOR signaling significantly suppresses prostate cancer cell and tumor organoid growth in vitro and experimental metastasis in vivo, suggesting that this can be a therapeutic approach against metastasizing prostate cancer.

cancer biology↗