TE Connectivity (France)

Tractography has emerged as a central tool for mapping the cerebral white matter architecture. However, its scientific value continues to be a subject of debate, given its inherent limitations in anatomical accuracy. This concise communication showcases key points of a debate held at the 2024 Tract-Anat Retreat, addressing the trade-offs between the accuracy and utility of tractography. While tractography remains constrained by limitations related to resolution, sensitivity, and validation, its usefulness and utility in areas such as surgical planning, disorder prediction, and the elucidation of brain development are emphasized. These perspectives highlight the necessity of context-specific interpretation, anatomically informed algorithms, and the continuous refinement of tractography workflows to achieve an optimal balance between accuracy and utility.

Ischaemic strokes disrupt brain networks, leading to remote effects in key regions like the thalamus, a critical hub for brain functions. However, non-invasive methods to quantify these remote consequences still need to be explored. This study aimed to demonstrate that MRI-derived R2* changes can capture iron accumulation linked with inflammation secondary to stroke-induced disconnection. To link remote R2* changes to stroke-induced disconnection, we first conducted a secondary analysis of 156 prospectively included stroke patients who underwent MRI at baseline and 1-year follow-up. We mapped fibres disconnected by baseline infarcts to compare the R2* changes over 1 year according to the disconnectivity status in specific thalamic nuclei groups. We also identified the variables associated with elevated R2* at 1 year in a multivariate context through linear regressions. In parallel, to understand the biological underpinning of the remote R2* changes, we set up a translational mouse model through photothrombotic induction of focal cortical infarcts or sham procedures in 110 C57BL/6J mice. We explored the mice through combinations of in vivo MRI at 72 h, 2-, 4- and 8-weeks, histology, qPCR for gene expression, mass spectrometry for iron concentration quantification and additional ex vivo high-resolution diffusion tensor imaging. In stroke patients, we found a significant increase of R2* within severely disconnected medial and lateral thalamic nuclei groups from baseline to 1 year. At the same time, no change occurred if these structures were not disconnected. We also showed that the disconnectivity status at baseline was significantly associated with R2* at follow-up, independently from confounders, establishing a direct and independent relationship between baseline disconnection and the subsequent R2* increase within the associated locations. In mice, we recapitulated the patients' conditions by observing increased R2* in the stroke groups, specifically within the disconnected thalamic nuclei. Such remote and focal R2* changes peaked at 2 weeks, preceding and correlating with longer-term atrophy at 8 weeks. We established that the remote R2* increase was spatially and temporally correlated with a significant increase of chemically determined iron load bound to ferritin within activated microglial cells. This study provides critical evidence that R2* is a sensitive marker of inflammation secondary to network disconnection, potentially informing future neuroprotective strategies targeting remote brain regions after stroke.

Over the past three decades, functional neuroimaging has amassed abundant evidence of the intricate interplay between brain structure and function. However, the potential anatomical and experimental overlap, independence, granularity, and gaps between functions remain poorly understood. Here, we show the latent structure of the current brain-cognition knowledge and its organisation. Our approach utilises the most comprehensive meta-analytic fMRI database (Neurosynth) to compute a three-dimensional embedding space–morphospace capturing the relationship between brain functions as we currently understand them. The space structure enables us to statistically test the relationship between functions expressed as the degree to which the characteristics of each functional map can be anticipated based on its similarities with others–the predictability index. The morphospace can also predict the activation pattern of new, unseen functions and decode thoughts and inner states during movie watching. The framework defined by the morphospace will spur the investigation of novel functions and guide the exploration of the fabric of human cognition.