Noninvasive functional and structural connectivity mapping of the human thalamocortical system

Abstract

Relating structural connectivity with functional activity is fundamentally important to understanding the brain's physiology. The thalamocortical system serves as a good model system for exploring structure/function relationships because of its well-documented anatomical connectivity. Here we performed functional and structural magnetic resonance mapping of the human thalamocortical system using intrinsic brain activity and diffusion-weighted imaging. The accuracy of these imaging techniques is tested by comparison with human histology registered to common anatomical space and connectional anatomy derived from nonhuman primates. In general, there is good overall concordance among structural, functional, and histological results which suggests that a simple model of direct anatomical connectivity between the cerebral cortex and the thalamus is capable of explaining much of the observed correlations in neuronal activity. However, important differences between structural and functional mapping results are also manifest which suggests a more complex interpretation and emphasizes the unique contributions from structural and functional mapping.

Figure 1.

Structural and functional connectivity between cerebral cortex and thalamus. (A) The cortex is partitioned on the basis of major anatomical landmarks into 5 nonoverlapping regions using surface-based ROI definition from CARET (Van Essen 2005; Van Essen et al. 2001). (B) Each cortical area demonstrated specific correlations in its intrinsic neuronal activity with distinct areas of the thalamus. (C) Probabilistic tractography likewise demonstrated specificity of tracking white matter fiber tracks between the thalamus and each cortical area, similar to Behrens et al. (2003). (D) Structural and functional mapping results demonstrated considerable overlap in their connectivity profiles (purple).

Figure 2.

Winner-take-all projections of the thalamic maps presented in Figure 1. Every thalamic voxel is labeled with the color of the cortical ROI that generated the highest partial correlation or highest tractography probability values using fcMRI and probabilistic DTI, respectively.

Figure 3.

Correspondence between structural/functional imaging and human histology. (A) Transverse section of the human thalamus showing histological labeling of various thalamic nuclei adapted and modified from Mai et al. (2008) (with copyright permission from the publisher Elsevier). (B) The white outline (highlighted by arrows) shows the overlap between structural and functional connectivity with motor/premotor cortex. Overlap region localizes to nuclei VL, VLP. (C) Overlap with prefrontal cortex localizes to MD, VA, and anterior nuclei. (D) Overlap with temporal cortex localizes to MGN. Principal cortical targets in the legend are derived from Jones (2007). (E) Overlap with parietal/occipital cortex localizes to lateral pulvinar. (F) Overlap with somatosensory cortex localizes to anterior pulvinar.

Figure 4.

Differences between observed structure and function. (A) Motor/premotor cortex functionally correlated with thalamic nuclei VL, VLP that are traditionally known to project principally to motor/premotor cortex. However, the locus of maximal correlation was observed in a more medial thalamic area (crosshairs). (B) This area of the thalamus (crosshairs) exhibits the highest probabilistic DTI tractography with prefrontal cortex. (C,D) The area in question (crosshairs) histologically is the lateral extent of the MD nucleus. Functional and structural mapping results are outlined in (C,D) on top of histology (Mai et al. 2008; with copyright permission from the publisher Elsevier). (E) Cortical localization using same partial correlation strategy and the same cortical ROIs defined in Figure 1A (thresholded at Z score of 5–15). Most of the cortical correlations are well-restricted to within the boundary of the cortical ROI that generated the map. The major exception to this rule is cortical localization using the prefrontal ROI. In addition to high correlations with most of the prefrontal cortex, there is clear localization with the DMN.