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

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 structurefunction 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.S ince early attempts to parcellate human and nonhuman cortex into structurally distinct subdivisions, the hypothesis that structural borders correspond to functional borders has been widely held (1-3). However, this hypothesis has been tested only rarely. Structural features such as sulci and gyri are commonly used to define anatomical regions in functional imaging, neurophysiology, and lesion studies, yet they have only a limited correspondence to more fine-grained structural organization such as cytoarchitecture (4-6). Microstructural borders based, for example, on measurements of cyto-, myelo-, or receptor architecture (7-9), can only be defined post mortem, and the methodological demands of such studies preclude investigation of the regional functional specializations in the same animals. Detailed testing of the relationship between these anatomicallybased measures and function based on comparisons between subjects is limited by the apparently substantial interindividual variations in microstructural anatomical boundaries (4-6).A structural feature that has not previously been used to define areal boundaries in the human neocortex is connectivity to other brain regions. Whereas features such as cytoarchitecture, myeloarchitecture, and receptor distributions distinguish the processing capabilities of a region, connectional anatomy constrains the nature of the information available to a region and the influence that it can exert over other regions in a distributed network. Therefore, not only does structural variation reflect functional organization, but local structural organization also determines local functional specialization. Data on brain connectivity in macaque monkeys show that cytoarchitectonically and functionally distinct regions of prefrontal cortex have distinct connectivity ''fingerprints'' (10). Differences in connectivity that parallel differences in cytoarchitecture have been used to define su...

Three-dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging: A meta-analysis

“…These two regions have been previously differentiated in the monkey (Dum and Strick, 1991;Matelli et al, 1991;Matsuzaka et al, 1992). Since then, this demarcation has been supported in humans across studies using cytoarchitectonic data (Vorobiev et al, 1998;Geyer et al, 2000a), PET (Fink et al, 1997), functional MRI (Deiber et al, 1999), diffusion tensor imaging , and diffusion weighted imaging (Johansen-Berg et al, 2004). The boundary between pre-SMA and SMA proper estimated by the ALE method remained consistent at y = 0mm throughout the coronal plane (Fig.…”

“…However, the anatomy of the cingulate sulcus is highly variable between subjects (Vogt et al, 1995;Paus et al, 1996), and cellularly the borders between MPMC and CMA can be difficult to define (Russo et al, 2002;Johansen-Berg et al, 2004). The ventral limit of MPMC, as determined by our analysis, varied depending on its rostro-caudal location (Fig.…”

MR connectomics: Principles and challenges

“…If human structural connection networks can be reliably partitioned into tens or hundreds of distinct network modules, then it is expected that these modules will correspond to functionally localized subdivisions of the brain. Indeed, connectionbased subdivisions of premotor cortex (Johansen-Berg et al, 2004) have been found to correspond closely to the subdivisions identified using functional imaging of motor and linguistic tasks in the same individuals, and connection-based subdivisions of thalamus (Zhang et al, 2008) as well as inferior frontal cortex (Anwander et al, 2007) and cingulate cortices (Beckmann et al, 2009) have been found to match the canonical functional parcellations of these areas. In a less function-specific vein, other groups have investigated the relationship, across the brain, between so-called "functional connectivity" which is assessed using correlations in resting-state BOLD signal with structural connectivity identified using diffusion imaging (Greicius et al, 2009;Hagmann et al, 2008;Honey et al, 2009;Koch et al, 2002;Skudlarski et al, 2008;van den Heuvel et al, 2008van den Heuvel et al, , 2009van den Heuvel et al, 2009;Van Dijk et al, 2010).…”

Functional and anatomical connectivity‐based parcellation of human cingulate cortex

“…Cross‐correlation was calculated between the rsFC patterns of all voxels in ROI and applied for automatic parcellation (Johansen‐Berg et al., 2004). …”