A phylogenetically-conserved axis of thalamocortical connectivity in the human brain

Abstract

The thalamus enables key sensory, motor, emotive, and cognitive processes via connections to the cortex. These projection patterns are traditionally considered to originate from discrete thalamic nuclei, however recent work showing gradients of molecular and connectivity features in the thalamus suggests the organisation of thalamocortical connections occurs along a continuous dimension. By performing a joint decomposition of densely sampled gene expression and non-invasive diffusion tractography in the adult human thalamus, we define a principal axis of genetic and connectomic variation along a medial-lateral thalamic axis. Projections along this axis correspond to an anterior-posterior cortical pattern and are aligned with electrophysiological properties of the cortex. The medial-lateral axis demonstrates phylogenetic conservation, reflects transitions in neuronal subtypes, and shows associations with neurodevelopment and common brain disorders. This study provides evidence for a supra-nuclear axis of thalamocortical organisation characterised by a graded transition in molecular properties and anatomical connectivity.

The spatial extent of anatomical connections within the thalamus varies across the cortical hierarchy in humans and macaques

“…We offer convergent evidence for this phenomenon by demonstrating that cortical areas that exhibit focal projections target posterolateral thalamus, whereas cortical areas that exhibit diffuse projections generally target anteromedial thalamus (55). This finding is consistent with previous studies showing the organization of thalamic functional connectivity, microstructure, and gene expression along the anteroposterior and mediolateral thalamic axis (16,21,56,(69)(70)(71). Prior work has shown that axon guidance cues along the anteromedial-posterolateral thalamic gradient shape the topography of thalamo-cortical connections (72).…”

“…Previous research has demonstrated that cortico-thalamic connectivity may continuously vary along the anteroposterior and mediolateral thalamic axes axes (16,21,61). Based on these data, we hypothesized that the extent of connections within the thalamus would also continuously vary along these axes.…”

“…This view has also been supported by evidence showing that certain cortical areas project to individual thalamic nuclei. However, some cortical areas exhibit widespread connections across the thalamus, projecting to multiple thalamic nuclei (15)(16)(17)(18)(19)(20)(21). One proposed role for such cross-nuclei targeting is to allow for spatial overlap of connections from different cortical areas, thereby facilitating information integration within the thalamus (22)(23)(24).…”

Cortical timescales and the modular organization of structural and functional brain networks

“…Likewise, the degree, PC, and WD of each cortical region is influenced by connections with subcortical ROIs and the community membership of those areas. We took this approach because many cortical areas have extensive connectivity to subcortical regions, and the patterning of these connections is thought to play a critical role in shaping the functional properties of the cerebral cortex (Alexander et al, 1986; Haber 2016; Müller et al, 2020; Oldham & Ball, 2023; Shepherd & Yamawaki, 2021). As such, accurately characterizing the topological properties of cortical areas necessarily requires considering connectivity with subcortical ROIs.…”

A sensorimotor-association axis of thalamocortical connection development

“…The thalamus is a bilateral gray matter structure in the diencephalon that sends (typically reciprocal) axonal projections throughout the human cortical mantle [16][17][18] . These direct thalamic projections to cortex are established in prenatal 19 and early postnatal 20 development, at which time they begin to have a profound effect on the formation and refinement of cortical circuits.…”