[Paper Review] Human brain parcellation using time courses of instantaneous connectivity

Erik S.B. van Oort, Maarten Mennes+6 more|arXiv (Cornell University)|Sep 15, 2016

Functional Brain Connectivity Studies12 references3 citations

TL;DR

This paper introduces a top-down functional parcellation method called Instantaneous Connectivity Parcellation (ICP) that subdivides brain regions using time courses of instantaneous functional connectivity. Applied to high-quality resting-state fMRI data, ICP successfully identifies biologically plausible sub-regions in the thalamus, entorhinal cortex, motor cortex, and subcortex—including brainstem and striatum—validated against cytoarchitectonic maps.

ABSTRACT

Functional neuroimaging studies have lead to understanding the brain as a collection of spatially segregated functional networks. It is thought that each of these networks is in turn composed of a set of distinct sub-regions that together support each network's function. Considering the sub-regions to be an essential part of the brain's functional architecture, several strategies have been put forward that aim at identifying the functional sub-units of the brain by means of functional parcellations. Current parcellation strategies typically employ a bottom-up strategy, creating a parcellation by clustering smaller units. We propose a novel top-down parcellation strategy, using time courses of instantaneous connectivity to subdivide an initial region of interest into sub-regions. We use split-half reproducibility to choose the optimal number of sub-regions. We apply our Instantaneous Connectivity Parcellation (ICP) strategy on high-quality resting-state FMRI data, and demonstrate the ability to generate parcellations for thalamus, entorhinal cortex, motor cortex, and subcortex including brainstem and striatum. We evaluate the subdivisions against available cytoarchitecture maps to show that the our parcellation strategy recovers biologically valid subdivisions that adhere to known cytoarchitectural features.

Motivation & Objective

• To develop a novel top-down parcellation strategy that identifies functional sub-units within larger brain regions, moving beyond traditional bottom-up clustering.
• To improve the biological plausibility of functional parcellations by aligning them with known cytoarchitectural boundaries.
• To evaluate whether time courses of instantaneous connectivity can reliably subdivide functionally homogeneous regions into distinct sub-regions.
• To establish a reproducible method for parcellation using split-half reliability to determine optimal sub-region count.
• To validate the resulting parcellations against existing histological maps to confirm anatomical and functional relevance.

Proposed method

• The method begins with an initial region of interest (ROI), such as the thalamus or motor cortex, defined a priori.
• Time courses of instantaneous connectivity are extracted between each voxel within the ROI and all other voxels, capturing dynamic functional relationships.
• These time courses are used as input for clustering to identify sub-regions with distinct connectivity dynamics.
• Split-half reproducibility is applied to assess consistency across data splits, used to select the optimal number of sub-regions.
• The clustering process is guided by temporal patterns in connectivity, emphasizing dynamic functional differentiation over static correlation.
• The final parcellation is evaluated for spatial coherence and alignment with known cytoarchitectural boundaries.

Experimental results

Research questions

• RQ1 Can time courses of instantaneous connectivity reliably subdivide a homogeneous brain region into functionally distinct sub-regions?
• RQ2 Does the proposed ICP method produce parcellations that are reproducible across data splits and biologically plausible?
• RQ3 How well do the ICP-derived sub-regions align with established cytoarchitectonic maps of the human brain?
• RQ4 Can the ICP approach be applied to subcortical and non-cortical regions, such as the thalamus and brainstem, where parcellation is particularly challenging?
• RQ5 Is the top-down ICP strategy more effective than bottom-up clustering in capturing functionally and anatomically meaningful subdivisions?

Key findings

• The Instantaneous Connectivity Parcellation (ICP) method successfully subdivided the thalamus, entorhinal cortex, motor cortex, and subcortical regions including the brainstem and striatum into functionally distinct sub-regions.
• ICP-generated parcellations demonstrated high split-half reproducibility, indicating robustness in sub-region identification.
• The resulting sub-regions showed strong spatial coherence and were consistent with known cytoarchitectural boundaries in the human brain.
• The method identified functionally heterogeneous sub-regions even in traditionally difficult-to-parcellate areas such as the subcortex.
• Validation against histological maps confirmed that ICP recovers biologically valid subdivisions, supporting its utility in functional brain mapping.
• The use of time courses of instantaneous connectivity enabled detection of dynamic functional differentiation not captured by standard correlation-based methods.