Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex

H Johansen-Berg, T E J Behrens, M D Robson, I Drobnjak, M F S Rushworth, J M Brady, S M Smith, D J Higham, P M Matthews, H Johansen-Berg, T E J Behrens, M D Robson, I Drobnjak, M F S Rushworth, J M Brady, S M Smith, D J Higham, P M Matthews

Abstract

A fundamental issue in neuroscience is the relation between structure and function. However, gross landmarks do not correspond well to microstructural borders and cytoarchitecture cannot be visualized in a living brain used for functional studies. Here, we used diffusion-weighted and functional MRI to test structure-function relations directly. Distinct neocortical regions were defined as volumes having similar connectivity profiles and borders identified where connectivity changed. Without using prior information, we found an abrupt profile change where the border between supplementary motor area (SMA) and pre-SMA is expected. Consistent with this anatomical assignment, putative SMA and pre-SMA connected to motor and prefrontal regions, respectively. Excellent spatial correlations were found between volumes defined by using connectivity alone and volumes activated during tasks designed to involve SMA or pre-SMA selectively. This finding demonstrates a strong relationship between structure and function in medial frontal cortex and offers a strategy for testing such correspondences elsewhere in the brain.

Figures

Fig. 1.
Fig. 1.
Medial frontal cortex mask shown in axial (Left, Z = 58) and sagittal (Right, X = -2) view. The vertical line indicates Y = 0 (vertical line from the anterior commissure). These two slices are used for the initial, single-slice parcellations of medial frontal cortex.
Fig. 2.
Fig. 2.
Connectivity-based parcellation of medial frontal cortex. (a and b) Result of parcellating a sagittal (a) and axial (b) slice in a single subject. Original (Left) and reordered (Center) cross-correlation matrices are shown. The clusters identified in the reordered matrices are indicated by the colored bar below the matrices. Black regions on the color bar represent elements that did not clearly belong to one cluster and were therefore unclassified. (Right) The images show the clusters mapped onto the brain by using the same color scheme as the color bar. For all subjects, clusters were present in the reordered matrices and were mapped onto discrete regions distributed along a posterior-anterior axis. The yellow line indicates Y = 0. For individual subject data see Supporting Text.(c) Population probability maps for putative SMA (red to yellow) and pre-SMA (blue to turquoise) shown for single sagittal (Left) and axial (Right) slices. Population maps have been thresholded to only include voxels where a cluster was present in four or more subjects (of nine). Green voxels represent overlap between SMA and pre-SMA. The crosshairs are positioned at Y = 0.
Fig. 3.
Fig. 3.
Testing structure-function correspondence. (a) Activation for a single subject during serial subtraction (red to yellow) and finger tapping (blue to turquoise). Voxels activated during both tasks are green. (b) Original (Left) and reordered (Right) connectivity cross-correlation matrix for all medial frontal voxels activated in either task for this subject. The reordered matrix was divided into two clusters (indicated by the colored bar). (c) When mapped onto the brain, the border between the connectivity-defined clusters corresponds closely to the boundary between the functionally activated volumes. Note that although clusters are shown for example slices in a and c, the matrices in b include all voxels from the 3D volume that was activated by either task and fell within the anatomically defined medial frontal mask. The matrices in this case are therefore typically much larger than the single-slice matrices shown in Fig. 2. For data from all subjects see Supporting Text.
Fig. 4.
Fig. 4.
Colocalization of structurally and functionally defined clusters for all subjects. Each point represents the center of gravity of an fMRI activation or connectivity-defined cluster for a single subject. Centers of activation during finger tapping (magenta) colocalize with connectivity-defined SMA (blue), whereas centers of activation during serial subtraction (black) colocalize with centers of connectivity-defined pre-SMA (red). Ellipses represent 85% confi-dence intervals. Dashed lines connect points from the same individual.
Fig. 5.
Fig. 5.
Connections from putative SMA and pre-SMA. (a) The population map of putative SMA (thresholded at more than four subjects) is purple. The group connectivity distribution ranges from blue to turquoise. Connections from putative SMA tended to go to the precentral gyrus [crosshairs in ai and the corticospinal tract (aii)]. (b) The population map for putative pre-SMA (more than four subjects) is brown. The group connectivity distribution from putative pre-SMA ranges from red to yellow. Connections from pre-SMA tended to go to the prefrontal cortex [crosshairs in bi show a termination point in the superior frontal gyrus) and medial parietal cortex (bii)]. (c) Group connectivity distributions from pre-SMA and SMA are rendered together for comparison (ci and cii). Connections from pre-SMA terminated in inferior frontal gyrus. In the precentral gyrus, connections from SMA terminated in caudal parts of the gyrus, corresponding to motor and premotor cortices, whereas pre-SMA connections terminated in more rostral, inferior parts of precentral gyrus (ciii). In the thalamus, connections from SMA traveled through the ventrolateral part of the thalamus and the adjacent internal capsule, whereas those from pre-SMA traveled through more anterior parts of the thalamus. Green regions in C represent overlap between connectivity distributions from SMA and pre-SMA. Coordinates given below each brain slice indicate the location of the crosshairs in MNI coordinates.

Source: PubMed

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