524997 research-article2014
MSJ0010.1177/1352458514524997Multiple Sclerosis JournalWojtowicz et al.
MULTIPLE SCLEROSIS MSJ JOURNAL
Research Paper
Altered functional connectivity and performance variability in relapsing– remitting multiple sclerosis
Multiple Sclerosis Journal 1–11 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1352458514524997 msj.sagepub.com
Magdalena Wojtowicz1, Erin L Mazerolle2, Virender Bhan3 and John D Fisk1,3,4,5
Abstract Background: Patients with multiple sclerosis (MS) demonstrate slower and more variable performance on attention and information processing speed tasks. Greater variability in cognitive task performance has been shown to be an important predictor of neurologic status and provides a unique measure of cognitive performance in MS patients. Objectives: This study investigated alterations in resting-state functional connectivity associated with within-person performance variability in MS patients. Methods: Relapsing–remitting MS patients and matched healthy controls completed structural MRI and resting-state fMRI (rsfMRI) scans, as well as tests of information processing speed. Performance variability was calculated from reaction time tests of processing speed. rsfMRI connectivity was investigated within regions associated with the default mode network (DMN). Relations between performance variability and functional connectivity in the DMN within MS patients were evaluated. Results: MS patients demonstrated greater reaction time performance variability compared to healthy controls (p0.05). Mean BOLD time series were extracted from 10 mm spheres centered on an anterior seed (ventral medial prefrontal cortex (vmPFC): x= −2, y= 49, z= −4) and a posterior seed (posterior cingulate cortex (PCC): x= −2, y= −30, z= 30) of the DMN25 and were used in a seed-based voxelwise connectivity analysis. These two seeds were selected as they are suggested to reflect two main hubs within the DMN9,26 and differences in functional connectivity have been reported for these two hubs in healthy individuals.26,27 Mean-centered individual standard deviations (ISD) scores from the three CTIP subtests were entered as covariates in the analysis. Images were cluster threshold corrected, z0.05). MS participants did not differ from controls on the SDMT, or the 2- and 3-second PASATs (p>0.05; Table 1). The MS group reported more fatigue symptoms but did not report more symptoms of depression than healthy controls. Lesion load and BPF are also presented in Table 1. The MS group demonstrated lower BPF than healthy controls (t(32)=2.49, p=0.018).
CTIP performance Accuracy data are not available for the SRT subtest. Mean accuracy did not differ between groups on the CTIP CRT (F(1, 32)= −0.217 p=0.83) or SSRT (F(1, 32)= −0.326, p= 0.75). On the CRT, mean (SD) errors for the MS group was 0.40(0.86) and 0.44(0.83) for the control group. On the SSRT, mean (SD) errors for the MS group was 1.0(1.33) and 0.88(0.81) for the control group. Group mean reaction times (RTs) for each CTIP subtest are shown in Table 2. A repeated-measures ANOVA
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Multiple Sclerosis Journal
Table 1. Demographic, clinical, and MRI metrics.
Age M (SD) Education (years) M(SD) SDMT M(SD) PASAT-3 M(SD) PASAT-2 M(SD) BDI-FS M(SD) D-FIS M(SD) EDSS scores Md(Range) Years onset Md(Range) Lesion volume (mL) M(SD) BPF M(SD)
MS patients
Controls
p
42.1(7.4) 14.7(1.8) 55.2(10.5) 45.3(8.2) 33.3(11.5) 1.9(2.07) 10.9(7.48) 2.25(1–3.5) 7.5(1–28) 16.7(25.7) 0.82(0.03)
43.1(7.8) 15.1(2.3) 60.6(10.2) 48.6(9.0) 36.9(9.6) 0.9(1.34) 2.3(3.01)a ___ ___ ___ 0.84(0.02)
0.70 0.58 0.14 0.27 0.33 0.10 0.001 __ __ __ 0.02
aN:15; SDMT: Symbol Digit Modalities Test; PASAT: Paced Auditory Serial Addition Test; BDI-FS: Beck Depression Inventory-Fast Screen; D-FIS: Daily Fatigue Impact Scale; EDSS: Expanded Disability Status Scale; BPF: Brain parenchymal fraction.
Table 2. CTIP performance for both groups. Measure
MS patients
Controls
p value
SRT-Mean RT M(SD) CRT-Mean RT M(SD) SSRT-Mean RT M(SD) SRT-ISD M(SD) CRT-ISD M(SD) SSRT-ISD M(SD)
399.45(59.74) 648.96(113.64) 952.12(127.52) 7.87(2.50) 8.20(3.92) 9.27(2.13)
337.24(56.77) 574.84(125.68) 824.54(168.76) 6.19(2.23) 7.02(3.20) 7.75(2.17)
0.004 0.080 0.018 0.048 0.349 0.047
CRT: choice reaction time; ISD: individual standard deviation; SSRT: semantic search reaction time; SRT: simple reaction time.
revealed that RTs increased as the tasks became more demanding (Test: F(2, 64)=334.63, p
MSJ0010.1177/1352458514524997Multiple Sclerosis JournalWojtowicz et al.
MULTIPLE SCLEROSIS MSJ JOURNAL
Research Paper
Altered functional connectivity and performance variability in relapsing– remitting multiple sclerosis
Multiple Sclerosis Journal 1–11 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1352458514524997 msj.sagepub.com
Magdalena Wojtowicz1, Erin L Mazerolle2, Virender Bhan3 and John D Fisk1,3,4,5
Abstract Background: Patients with multiple sclerosis (MS) demonstrate slower and more variable performance on attention and information processing speed tasks. Greater variability in cognitive task performance has been shown to be an important predictor of neurologic status and provides a unique measure of cognitive performance in MS patients. Objectives: This study investigated alterations in resting-state functional connectivity associated with within-person performance variability in MS patients. Methods: Relapsing–remitting MS patients and matched healthy controls completed structural MRI and resting-state fMRI (rsfMRI) scans, as well as tests of information processing speed. Performance variability was calculated from reaction time tests of processing speed. rsfMRI connectivity was investigated within regions associated with the default mode network (DMN). Relations between performance variability and functional connectivity in the DMN within MS patients were evaluated. Results: MS patients demonstrated greater reaction time performance variability compared to healthy controls (p0.05). Mean BOLD time series were extracted from 10 mm spheres centered on an anterior seed (ventral medial prefrontal cortex (vmPFC): x= −2, y= 49, z= −4) and a posterior seed (posterior cingulate cortex (PCC): x= −2, y= −30, z= 30) of the DMN25 and were used in a seed-based voxelwise connectivity analysis. These two seeds were selected as they are suggested to reflect two main hubs within the DMN9,26 and differences in functional connectivity have been reported for these two hubs in healthy individuals.26,27 Mean-centered individual standard deviations (ISD) scores from the three CTIP subtests were entered as covariates in the analysis. Images were cluster threshold corrected, z0.05). MS participants did not differ from controls on the SDMT, or the 2- and 3-second PASATs (p>0.05; Table 1). The MS group reported more fatigue symptoms but did not report more symptoms of depression than healthy controls. Lesion load and BPF are also presented in Table 1. The MS group demonstrated lower BPF than healthy controls (t(32)=2.49, p=0.018).
CTIP performance Accuracy data are not available for the SRT subtest. Mean accuracy did not differ between groups on the CTIP CRT (F(1, 32)= −0.217 p=0.83) or SSRT (F(1, 32)= −0.326, p= 0.75). On the CRT, mean (SD) errors for the MS group was 0.40(0.86) and 0.44(0.83) for the control group. On the SSRT, mean (SD) errors for the MS group was 1.0(1.33) and 0.88(0.81) for the control group. Group mean reaction times (RTs) for each CTIP subtest are shown in Table 2. A repeated-measures ANOVA
Downloaded from msj.sagepub.com at UNIVERSITE LAVAL on March 3, 2015
4
Multiple Sclerosis Journal
Table 1. Demographic, clinical, and MRI metrics.
Age M (SD) Education (years) M(SD) SDMT M(SD) PASAT-3 M(SD) PASAT-2 M(SD) BDI-FS M(SD) D-FIS M(SD) EDSS scores Md(Range) Years onset Md(Range) Lesion volume (mL) M(SD) BPF M(SD)
MS patients
Controls
p
42.1(7.4) 14.7(1.8) 55.2(10.5) 45.3(8.2) 33.3(11.5) 1.9(2.07) 10.9(7.48) 2.25(1–3.5) 7.5(1–28) 16.7(25.7) 0.82(0.03)
43.1(7.8) 15.1(2.3) 60.6(10.2) 48.6(9.0) 36.9(9.6) 0.9(1.34) 2.3(3.01)a ___ ___ ___ 0.84(0.02)
0.70 0.58 0.14 0.27 0.33 0.10 0.001 __ __ __ 0.02
aN:15; SDMT: Symbol Digit Modalities Test; PASAT: Paced Auditory Serial Addition Test; BDI-FS: Beck Depression Inventory-Fast Screen; D-FIS: Daily Fatigue Impact Scale; EDSS: Expanded Disability Status Scale; BPF: Brain parenchymal fraction.
Table 2. CTIP performance for both groups. Measure
MS patients
Controls
p value
SRT-Mean RT M(SD) CRT-Mean RT M(SD) SSRT-Mean RT M(SD) SRT-ISD M(SD) CRT-ISD M(SD) SSRT-ISD M(SD)
399.45(59.74) 648.96(113.64) 952.12(127.52) 7.87(2.50) 8.20(3.92) 9.27(2.13)
337.24(56.77) 574.84(125.68) 824.54(168.76) 6.19(2.23) 7.02(3.20) 7.75(2.17)
0.004 0.080 0.018 0.048 0.349 0.047
CRT: choice reaction time; ISD: individual standard deviation; SSRT: semantic search reaction time; SRT: simple reaction time.
revealed that RTs increased as the tasks became more demanding (Test: F(2, 64)=334.63, p
