Reynaud, O. | bioRxiv Science

bioRxiv2022

Concurrent TMS-fMRI to determine adaptive brain changes to virtual lesions interfering with visual processing

Understanding how focal perturbations lead to large-scale network (re)organization is essential for accurately predicting the behavioral consequences of brain lesions. In this study, we applied a virtual lesion approach by means of short bursts of 10 Hz transcranial magnetic stimulation (TMS) over either early visual areas (EVA) or the medio-temporal area (MT) in healthy participants, while acquiring concurrent functional MRI. TMS delivered during the early stages of motion processing selectively impaired direction discrimination at both sites, while global motion perception remained unaffected. These behavioral effects were accompanied by a common local increase in BOLD activity, but distinct patterns of network reorganization. Perturbation of EVA led to more robust and efficient functional adaptation, suggesting greater resilience to focal disruption. In contrast, behavioral impairments following MT stimulation were associated with a less organized, more random network structure. Together, these findings underscore the potential of TMS-fMRI coupling as a powerful approach for mapping causal disconnectomics--the dynamic relationships between localized neural disruption and widespread functional and behavioral outcomes providing a better understanding of lesion-induced brain changes in neurological disorders such as stroke. HighlightsO_LITMS-induced perturbation of the early visual areas (EVA) or the mediotemporal area (MT) area selectively impairs motion direction discrimination. C_LIO_LIThe TMS perturbation is associated with a context-dependent local up-scaling of BOLD activity in both areas. C_LIO_LIThe two visual areas display distinct topological networks adaptation in response to TMS, reflecting different levels of network resilience to a focal lesion. C_LIO_LITMS-fMRI coupling can be used to assess causal disconnectomics and to precisely map how a local perturbation propagates to large-scale behavioural deficits. C_LI

neuroscience↗

bioRxiv2021

Role of autophagy in sepsis-induced skeletal muscle dysfunction, whole-body metabolism, and survival

Septic patients frequently develop skeletal muscle wasting and weakness, resulting in severe clinical consequences and adverse outcomes. Autophagy is a stress-induced degradative process essential to cell survival. Recent studies have demonstrated that sepsis triggers sustained induction of autophagy in skeletal muscles, although the impact of this enhanced autophagy on sepsis-induced muscle dysfunction remains unclear. Atg7 is an autophagy gene that plays a major role in autophagosome formation. Using an inducible and muscle-specific Atg7 knockout mouse model (Atg7iSkM-KO), we investigated the functional importance of skeletal muscle autophagy in sepsis. Sepsis was induced using cecal ligation and perforation (CLP) with a sham operation serving as a control. Atg7iSkM-KO mice exhibited a more severe phenotype in response to sepsis, marked by severe muscle wasting and contractile dysfunction, hypoglycemia, higher ketone levels and a decreased in survival as compared to mice with intact Atg7. Several genes that encode 26S proteasome subunits were upregulated, suggesting that activation of the ubiquitin-proteasome system is responsible for the severe muscle atrophy that was seen in these mice. Sepsis and Atg7 deletion resulted in the accumulation of mitochondrial dysfunction, although sepsis did not further worsen mitochondrial dysfunction in Atg7iSkM-KO mice. Overall, our study demonstrates that autophagy inactivation in skeletal muscles triggers significant worsening of sepsis-induced contractile and metabolic dysfunctions and negatively impacts survival. Induction of autophagy in skeletal muscles in response to sepsis thus represents a protective mechanism.

cell biology↗