Movahedian Attar, F. | Search bioRxiv

bioRxiv2024

Connectivity at fine scale: mapping structural connective fields by tractography of short association fibres in vivo

The extraordinary number of short association fibres (SAF) connecting neighbouring cortical areas is a prominent feature of the large gyrified human brain. The contribution of SAF to the human connectome is largely unknown because of methodological challenges in mapping them. We present a method to characterise cortico-cortical connectivity mediated by SAF in topologically organised cortical areas. We introduce the structural connective fields (sCF) metric which specifically quantifies neuronal signal propagation and integration mediated by SAF. This new metric complements functional connective field metrics integrating across contributions from short- and long-range white matter and intracortical fibres. Applying the method in the human early visual processing stream, we show that SAF preserve cortical functional topology. Retinotopic maps of V2 and V3 could be predicted from retinotopy in V1 and SAF connectivity. The sCF sizes increased along the cortical hierarchy and were smaller than their functional counterparts, in line with the latter being additionally broadened by long-range and intracortical connections. In vivo sCF mapping provides insights into short-range cortico- cortical connectivity in humans comparable to tract tracing studies in animal research and is an essential step towards creating a complete human connectome. HighlightsO_LINon-invasive mapping of Short Association Fibre (SAF) connectivity via diffusion-weighted MRI-based probabilistic tractography accurately predicted cortical functional neuroanatomy. C_LIO_LIThe novel structural Connective Fields (sCF) concept provides a quantitative measure of cortico-cortical integration facilitated by SAF, complementing the existing functional Connective Field (CF) concept. C_LIO_LISub-millimeter resolution diffusion-weighted MRI enables tractography and connective field modeling of SAF, unlocking applications previously restricted to invasive tract tracing in animal studies. C_LI

neuroscience↗

bioRxiv2020

CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer

Some breast tumors metastasize aggressively whereas others remain in a state of metastatic dormancy for months or even years. The mechanism governing such metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping in mice, we identified a discrete population of CD39+PD-1+CD8+ T cells present both in primary tumors and in dormant metastasis, which was hardly found in aggressively metastasizing tumors. Using blocking antibodies, we found that dormancy depended on TNF and IFN{gamma}. Of note, immunotherapy reduced the number of dormant cancer cells in the lungs. Adoptive transfer of purified CD39+PD-1+CD8+ T cells prevented metastatic outgrowth. In human breast cancer, the frequency of CD39+PD-1+CD8+ but not of total CD8+ T cells correlated with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39+PD-1+CD8+ T cells for controlling experimental and human breast cancer. Furthermore, density of CD39+PD-1+CD8+ T cells may serve as a novel biomarker and may serve as a potential immunotherapy target. Thus, we discovered that a primary breast tumor primes a systemic, CD39+PD-1+CD8+ T cell response that is essential for metastatic dormancy in the lungs.

cancer biology↗