Emanuele Pravata MD, Presenter: Nothing to Disclose

Carlo Sestieri PhD, Abstract Co-Author: Nothing to Disclose

Massimo Caulo MD, PhD, Abstract Co-Author: Nothing to Disclose

Gianna Riccitelli PhD, Abstract Co-Author: Nothing to Disclose

Chiara Zecca MD, Abstract Co-Author: Nothing to Disclose

Alessandro Cianfoni, Abstract Co-Author: Nothing to Disclose

Claudio Gobbi MD, Abstract Co-Author: Nothing to Disclose

To investigate changes of the resting-state functional connectivity (RS-FC) MRI induced by the execution of a cognitively effortful task in patients with relapsing-remitting multiple sclerosis (RRMS) with cognitive fatigue (CF).

22 clinically stable RRMS patients, 11 with CF (F) and 11 without CF (nF) according to the Fatigue Scale for Motor and Cognitive Functions (FSMC) and 12 age- and gender-matched healthy control subjects (HS). RS-FC scans were acquired on a 3T MR scanner immediately before (t0), immediately after (t1) and 20 minutes after (t2) execution of the Paced Auditory Serial Addition Test (PASAT). Differences in the RS-FC strength between each brain voxel and the rest of the gray matter between F, nF and HS were investigated at each time point using a data-driven intrinsic connectivity contrast technique [Martuzzi et al, Neuroimage 2011] and 1-way between-subjects ANOVAs. The presence of a correlation between significant t2 and t2-t0 RS-FC differences and neuropsychological measures across patients was investigated. Structural and diffusion-tensor (20 gradient directions) data were acquired to evaluate atrophy, lesion load and white matter microstructure.

T2-hyperintense lesion load and brain atrophy did not differ between F and nF. Self-reported CF after PASAT (PASAT-F) was significantly higher in F than nF patients and HS (p=0.016, Mann-Whitney U test). Compared to nF and HS, F patients presented stronger RS-FC at t2 between the left dorsolateral prefrontal cortex (L-DLPFC) and pre-motor (Figure), secondary visual, left frontal and temporal areas (p=0.01, FDR-corrected). The RS-FC strength of these links at t2 and t0-t2 difference positively correlated with FSMC (rho=0.65-0.73, p=0.001) and PASAT-F (rho=0.4-0.59, p=0.044-0.02). Tractographic reconstructions of cortico-thalamic projection fibers, using L-DLPFC as a seed region, showed reduced fractional anisotropy in F compared to nF patients (0.39 vs. 0.43, p=0.047).

In RRMS patients, the degree of CF is related to persistence of hyperconnectivity within fronto-temporo-occipital networks despite relax after mental effort, and to disconnection of thalamo-cortical projection links.

Identification of functional imaging biomarkers of CF, explaining RRMS patients' reduced resilience, may help clinical diagnosis and response assessment to specific medical and rehabilitative treatments.

Pravata, E, Sestieri, C, Caulo, M, Riccitelli, G, Zecca, C, Cianfoni, A, Gobbi, C, Brain Intrinsic Resting-state Functional Connectivity Modulation Induced by Mental Effort in Multiple Sclerosis Patients with Fatigue.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14014467.html