Cognitive processing speed deficits are common in multiple sclerosis (MS). Despite this, the exact neural mechanism underlying slowed information processing speed remains unknown. Furthermore, functional magnetic resonance imaging (fMRI) using only blood-oxygen-level-dependent signal may not be sensitive to MS-related metabolic changes affecting processing speed ability. Previous work has shown that cerebral metabolism in motor and visual areas are associated with performance on motor and visual tasks, however, it is unknown if task-based metabolism in the dorso-lateral prefrontal cortex (dlPFC), a region known to be involved in processing speed, is related to the slowed processing speed observed in MS.
We aim to assess whether metabolism in the dlPFC, a processing speed region, is associated with MS-related processing speed deficits.
MS and healthy control (HC) participants who met inclusion criteria were scanned using a 3T MRI scanner with a dualecho calibrated fMRI (cfMRI) sequence which provided nearsimultaneous measures for both cerebral blood flow (CBF) and BOLD signal. During imaging, participants performed a block-design digit-symbol substitution task (DSST) that required the viewing of a digit-symbol pairing key and responding as to whether a probe digit-symbol pair matched the key as fast as they could using button boxes. A hypercapnia gas challenge involving periodic inhalation of room air (4 min) and 5% CO2 (6 min) permitted measures of cerebral metabolic rate of oxygen (CMRO2). Data were preprocessed and average percent signal change from baseline was calculated in each voxel providing BOLD and CBF time series. The anatomical region of interest (ROI) was defined as dlPFC after Freesurfer cortical parcellation. Regression analyses were performed controlling for ROI size to assess whether BOLD, CBF, or CMRO2 could explain variability in processing speed ability.
An independent-samples t-test showed that the MS group had a significantly higher response time (RT) for the DSST (t[50]=3.12, p=.003) compared to HCs. Within the MS group, regression analyses using RT for correct trials as the dependent factor were not significant for BOLD and CBF PSC but was significant for CMRO2 (R2=.170, p=.053) after controlling for number of voxels within the ROI. No regression analyses were significant within the HC group.
Our analyses suggest that metabolism, not BOLD or CBF, in dlPFC, a region known to involved in processing speed, explains MS-related slowed processing speed.