Network structure of the mouse brain connectome with voxel resolution

Abstract

Fine-grained descriptions of brain connectivity are required to understand how neural information is processed and relayed across spatial scales. Previous investigations of the mouse brain connectome have used discrete anatomical parcellations, limiting spatial resolution and potentially concealing network attributes critical to connectome organization. Here, we provide a voxel-level description of the network and hierarchical structure of the directed mouse connectome, unconstrained by regional partitioning. We report a number of previously unappreciated organizational principles in the mammalian brain, including a directional segregation of hub regions into neural sink and sources, and a strategic wiring of neuromodulatory nuclei as connector hubs and critical orchestrators of network communication. We also find that the mouse cortical connectome is hierarchically organized along two superimposed cortical gradients reflecting unimodal-transmodal functional processing and a modality-specific sensorimotor axis, recapitulating a phylogenetically conserved feature of higher mammals. These findings advance our understanding of the foundational wiring principles of the mammalian connectome.

Unique spatiotemporal fMRI dynamics in the awake mouse brain

“…Our investigations show that the overall static architecture of rsfMRI networks in awake mice reconstitutes organizational principles observed in anesthetized conditions, including the presence of distributed systems such as a DMN, a LCN and a salience-like network. Analogous between-state correspondences in anesthesia and awake conditions have been reported in rats (Liang et al, 2012a), primates (Xu et al, 2019;Hori et al, 2020b) and humans (Boveroux et al, 2010;Akeju et al, 2014), underscoring a tight relationship between the general spatial structure of spontaneous fMRI activity, and its underlying structural map (Alstott et al, 2009;Coletta et al, 2020).…”

“…Within this framework, the observed segregation of medial corticolimbic and postero-lateral visuoauditory cortical portions of the DMN in awake states is of interest, as it highlights a focal, state-dependent network reconfiguration occurring in awake rodents (including rats, Liang et al, 2012b), that however does not appear to have a direct correlate in higher mammalians (Vincent et al, 2007), with the possible exception of new world primates (Liu et al, 2019). As this segregation affects a widely-distributed community of monosynaptic connections (Coletta et al, 2020;Whitesell et al, 2021), we speculate it could reflect a dominant configuration aimed to enable increased cortical information capacity (i.e. the ensuing number of discriminable activity patterns), in the otherwise poorly differentiated rodent posterolateral cortex (Alkire et al, 2008;Iurilli et al, 2012;Buckner and Krienen, 2013).…”

“…Our deconstruction of awake rsfMRI activity in recurring CAPs revealed a unique dynamic structure recapitulating foundational principles of network organization in conscious primates and humans, including (a) the identification of a largely state-dominant CAPs characterized by a rich topographical organization, not rigidly anchored to the axonal structure (Barttfeld et al, 2015) and by prominent anti-coordination between visual-auditory and DMN regions (Demertzi et al, 2019); (b) stereotypic temporal trajectories in which state-specific CAPs are configured as dominant network attractors (Huang et al, 2020). By contrast, anesthetized state was associated with dominant temporal states that are topographically shaped by the underlying axonal structure with extensively integrated DMN and visual-auditory regions (Gutierrez- Barragan et al, 2019;Coletta et al, 2020). These findings are consistent with prior theoretical conceptualizations of conscious network activity as a balanced recurrence of intermittent epochs of segregated and global brain synchronization (Demertzi et al, 2013).…”

“…B) Between group connectivity differences (twosample T-test, p < 0.01, FWER corrected with defining threshold T=2.8). C) Group averaged voxel-wise FC matrices for each condition, with voxels organized within axonal connectivity modules (Coletta et al, 2020), and further partitions into network submodules. The sub-module corresponding to thalamic voxels within the LCN is not labeled (light-red block).…”

Promisomics and the Short-Circuiting of Mind

“…Let us be clear, there is a priori nothing wrong with industriously performing detailed biological work. Detailed neural mappings in organisms such as the larval fruit fly ( Eichler et al, 2017 ), adult fruit fly ( Zheng et al, 2018 ; Hulse et al, 2020 ; Li et al, 2020 ; Scheffer et al, 2020 ), larval zebrafish ( Hildebrand et al, 2017 ), or mice ( Oh et al,2014 ; Winnubst et al, 2019 ; Coletta et al, 2020 ) shed light onto facts and principles of neural organization. Connectomes can indeed be very useful to understand how simple motor patterns are generated.…”