Journal Article

Mapping Activity and Functional Organisation of the Motor and Visual Pathways Using ADC‐fMRI in the Human Brain

Riedmatten, Ines, Spencer, Arthur P. C., Perot, Jean‐Baptiste, Olszowy, Wiktor, Jelescu, Ileana, Nguyen‐Duc, Jasmine

2025

Overview

In contrast to blood‐oxygenation level‐dependent (BOLD) functional MRI (fMRI), which relies on changes in blood flow and oxygenation levels to infer brain activity, diffusion fMRI (DfMRI) investigates brain dynamics by monitoring alterations in the apparent diffusion coefficient (ADC) of water. These ADC changes may arise from fluctuations in neuronal morphology, providing a distinctive perspective on neural activity. The potential of ADC as an fMRI contrast (ADC‐fMRI) lies in its capacity to reveal neural activity independently of neurovascular coupling, thus yielding complementary insights into brain function. To demonstrate the specificity and value of ADC‐fMRI, both ADC‐ and BOLD‐fMRI data were collected at 3 T in human subjects during visual stimulation and motor tasks. The first aim of this study was to identify an acquisition design for ADC that minimises BOLD contributions. By examining the timings in responses, we report that ADC 0/1 timeseries (acquired with b values of 0 and 1 ms/μm2 $$ {\\upmu \\mathrm{m}}^2 $$ ) exhibit residual vascular contamination, while ADC 0.2/1 timeseries (with b values of 0.2 and 1 ms/μm2 $$ {\\upmu \\mathrm{m}}^2 $$ ) show minimal BOLD influence and higher sensitivity to neuromorphological coupling. Second, a general linear model was employed to identify activation clusters for ADC 0.2/1 and BOLD, from which the average ADC and BOLD responses were calculated. The negative ADC response exhibited a significantly reduced delay relative to the task onset and offset as compared to BOLD. This early onset further supports the notion that ADC is sensitive to neuromorphological rather than neurovascular coupling. Remarkably, in the group‐level analysis, positive BOLD activation clusters were detected in the visual and motor cortices, while the negative ADC clusters mainly highlighted pathways in white matter connected to the motor cortex. In the averaged individual level analysis, negative ADC activation clusters were also present in the visual cortex. This finding confirmed the reliability of negative ADC as an indicator of brain function, even in regions with lower vascularisation such as white matter. Finally, we established that ADC‐fMRI time courses yield the expected functional organisation of the visual system, including both grey and white matter regions of interest. Functional connectivity matrices were used to perform hierarchical clustering of brain regions, where ADC‐fMRI successfully reproduced the expected structure of the dorsal and ventral visual pathways. This organisation was not replicated with the b = 0.2 ms/μm2 $$ {\\upmu \\mathrm{m}}^2 $$diffusion‐weighted time courses, which can be seen as a proxy for BOLD (via T2‐weighting). These findings underscore the robustness of ADC time courses in functional MRI studies, offering complementary insights into BOLD‐fMRI regarding brain function and connectivity patterns. This article validates ADC‐fMRI as a tool complementing BOLD‐fMRI, detecting neural activity via neuromorphological coupling. In experiments with motor and visual stimuli at 3 T, ADC‐fMRI was shown to be less prone to vascular contamination and to capture white matter activity.

• Publisher: John Wiley & Sons, Inc
• Subject: Activation analysis / Adult / apparent diffusion coefficient / Blood flow / Blood levels / BOLD / Brain / Brain - diagnostic imaging / Brain - physiology / Brain mapping / Brain Mapping - methods / Cerebral blood flow / Cluster analysis / Clustering / Cortex (motor) / Coupling / Diffusion coefficient / Diffusion Magnetic Resonance Imaging - methods / diffusion MRI / Female / fMRI / functional connectivity / Functional magnetic resonance imaging / Humans / Image Processing, Computer-Assisted / Magnetic resonance imaging / Magnetic Resonance Imaging - methods / Male / Motor Cortex - diagnostic imaging / Motor Cortex - physiology / Neural networks / Oxygen - blood / Oxygenation / Photic Stimulation / Sensorimotor integration / Substantia alba / Visual cortex / Visual pathways / Visual Pathways - diagnostic imaging / Visual Pathways - physiology / Visual perception / Visual stimuli / Visual system / Visual tasks / Young Adult