To investigate the dynamic temporal changes of brain resting-state functional connectivity (RS-FC) following mental effort in multiple sclerosis (MS) patients with cognitive fatigue (CF).
Methods:
Twenty-two MS patients, 11 with (F) and 11 without CF, and 12 healthy controls were included. Separate RS-FC scans were acquired on a 3T MR scanner immediately before (t0), immediately after (t1) and 30 minutes after (t2) execution of the paced auditory serial addition test (PASAT), a cognitively demanding task. Subjectively perceived CF after PASAT execution was also assessed. RS-FC changes were investigated by using a data-driven approach (the Intrinsic Connectivity Contrast-power), complemented by a priori defined regions of interest analyses.
Results:
The F-group patients experienced stronger RS-FC at t2 between the left superior frontal gyrus (L-SFG) and occipital, frontal and temporal areas, which increased over time after PASAT execution. In the F-group patients, the L-SFG was hyperconnected at t1 with the left caudate nucleus and hypoconnected at t2 with the left anterior thalamus. These variations were correlated with both subjectively perceived and clinically assessed CF, and—for the left thalamus—with PASAT performance.
Conclusion:
The development of cortico–cortical and cortico–subcortical hyperconnectivity following mental effort is related to CF symptoms in MS patients.
ChaudhuriABehanPO. Fatigue and basal ganglia. J Neurol Sci2000; 179(1–2): 34–42.
3.
RoelckeUKapposLLechner-ScottJ. Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: A 18F-fluorodeoxyglucose positron emission tomography study. Neurology1997; 48(6): 1566–1571, http://www.ncbi.nlm.nih.gov/pubmed/9191767
4.
DeLucaJGenovaHMHillaryFG. Neural correlates of cognitive fatigue in multiple sclerosis using functional MRI. J Neurol Sci2008; 270(1–2): 28–39, http://www.ncbi.nlm.nih.gov/pubmed/18336838
5.
GenovaHMRajagopalanVDeLucaJ. Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging. PLoS ONE2013; 8(11): e78811 (1–10 pp.).
6.
EngströmMFlensnerGLandtblomAM. Thalamo-striato-cortical determinants to fatigue in multiple sclerosis. Brain Behav2013; 3(6): 715–728.
CordesDHaughtonVMArfanakisK. Mapping functionally related regions of brain with functional connectivity MR imaging. Am J Neuroradiol2000; 21(9): 1636–1644, http://www.ncbi.nlm.nih.gov/pubmed/11039342
TartagliaMCNarayananSArnoldDL. Mental fatigue alters the pattern and increases the volume of cerebral activation required for a motor task in multiple sclerosis patients with fatigue. Eur J Neurol2008; 15(4): 413–419, http://www.ncbi.nlm.nih.gov/pubmed/18353127
12.
AnticevicAHuSZhangS. Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol Psychiatry2013; 75(8): 595–605, http://www.ncbi.nlm.nih.gov/pubmed/24314349
KurtzkeJF. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology1983; 33(11): 1444–1452, http://www.ncbi.nlm.nih.gov/pubmed/6685237
20.
BenedictRHBFishmanIMcClellanMM. Validity of the beck depression inventory-fast screen in multiple sclerosis. Mult Scler2003; 9(4): 393–396, http://www.ncbi.nlm.nih.gov/pubmed/12926845
DagenaisERouleauIDemersM. Value of the MoCA test as a screening instrument in multiple sclerosis. Can J Neurol Sci2013; 40(3): 410–415, http://www.ncbi.nlm.nih.gov/pubmed/23603179
23.
PennerIKRaselliCStöcklinM. The Fatigue Scale for Motor and Cognitive Functions (FSMC): Validation of a new instrument to assess multiple sclerosis-related fatigue. Mult Scler2009; 15(12): 1509–1517.
24.
DeLucaJJohnsonSKNatelsonBH. Information processing efficiency in chronic fatigue syndrome and multiple sclerosis. Arch Neurol1993; 50(3): 301–304.
LeeHWSpencerDDConstableRT. Altered functional connectivity in seizure onset zones revealed by fMRI intrinsic connectivity. Neurology2014; 83: 2269–2277.
27.
Whitfield-GabrieliSNieto-CastanonA. Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect2012; 2(3): 125–141, http://www.ncbi.nlm.nih.gov/pubmed/22642651
28.
Tzourio-MazoyerNLandeauBPapathanassiouD. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage2002; 15(1): 273–289.
29.
ZhangDSnyderAZFoxMD. Intrinsic functional relations between human cerebral cortex and thalamus. J Neurophysiol2008; 100(4): 1740–1748.
30.
LehSEPtitoAChakravartyMM. Fronto-striatal connections in the human brain: A probabilistic diffusion tractography study. Neurosci Lett2007; 419(2): 113–118.
AudoinBIbarrolaDRanjevaJP. Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS. Hum Brain Mapp2003; 20(2): 51–58, http://www.ncbi.nlm.nih.gov/pubmed/14505331
33.
ChiaravallotiNHillaryFRickerJ. Cerebral activation patterns during working memory performance in multiple sclerosis using FMRI. J Clin Exp Neuropsychol2005; 27: 33–54.
HawellekDJHippJFLewisCM. Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis. Proc Natl Acad Sci U S A2011; 108(47): 19066–19071.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
