Author Of 6 Presentations
P0008 - Divergent patterns of ventral attention network centrality relate to cognitive conversion in MS (ID 473)
Abstract
Background
Cognitive impairment (CI) is common in multiple sclerosis (MS), but due to a lack of longitudinal data it remains unclear which mechanisms relate to conversion to mild or even severe CI. Previous cross-sectional work has suggested the importance of cognition-related resting-state networks, such as the default-mode and attention networks.
Objectives
To characterize the functional network changes related to conversion to CI in a large sample of MS patients over a period of 5 years.
Methods
A total of 233 MS patients and 59 healthy controls (HC), all part of the Amsterdam MS cohort, underwent extensive neuropsychological testing and resting-state fMRI at baseline and follow-up (mean time-interval 4.9±0.9 years). At baseline, MS patients were categorized as being cognitively impaired (scoring ≤-2 SD on ≥2 domains, N=74), mildly impaired (MCI, being impaired on 1 domain or scoring between -1.5 and -2SD on ≥2 domains, N=33) or preserved (CP, not fulfilling the CI or MCI criteria, N=126). In addition, these groups were categorized according to the group to which they converted at follow-up (e.g. CP to CI). Network function was quantified using eigenvector centrality, a measure of network importance, which was averaged over established resting-state networks at both time-points. Correlations with brain volumes were calculated.
Results
Over time, 26.2% of CP patients deteriorated and developed MCI (66.7%) or CI (33.3%) and 73.8% remained CP. 23.5% of MCI patients, progressed to CI. Centrality analysis showed that patients who were CI at baseline demonstrated a higher cross-sectional DMN centrality compared to controls (P=.05). Longitudinally, patients who remained CP and CP-to-MCI converters showed increasing ventral attention network (VAN) centrality over time time (P=.017 and .008, respectively), , whereas in the MCI and CI converter groups this increase was absent. Patients with less severe deep gray matter atrophy at baseline showed stronger increases in VAN centrality over time.
Conclusions
We showed that conversion from intact cognition to impairment in MS is related to an increase in centrality of the VAN, which is absent when overt impairment has manifested, then shifting towards DMN dysfunction. As the ventral attention network is known to normally relay information to the DMN, our results suggest that developing cognitive impairment is related to a progressive loss of control over the DMN by means of VAN dysfunction.
P0582 - High resolution functional mapping of upper and lower limb sensorimotor function in minimally disabled people with multiple sclerosis using 7T MRI (ID 1050)
Abstract
Background
In multiple sclerosis (MS) upper and lower limbs can be affected, but impairments only moderately relate to each other. Previous motor task studies have focussed predominantly on imaging hand function at clinical field strengths, preventing the detection of subtle changes and differentiation of mechanisms underlying subtle motor impairment.
Objectives
To investigate functional brain changes related to upper and/or lower limb motor task performance in minimally disabled MS patients using ultra-high field MRI.
Methods
Twenty-eight MS patients and seventeen healthy controls underwent visually-guided force-matching fMRI tasks using either hand or foot. Task performance (force error and lag) and activation level during upper and lower limb movements were compared between groups. Correlations were assessed between task activation and behavioural performance.
Results
During lower limb force tracking, MS patients showed significantly (p<0.01) longer lag, higher force error, higher primary motor and premotor cortex activation and lower cerebellar Crus I/II activation, compared to controls. No differences were seen in upper limb performance or activation. Upper and lower limb task performance was related to the level of activation in cerebellar, visual and motor areas in MS patients.
Conclusions
Altered lower limb movements and brain activation with preserved upper limb function and activation in minimally disabled patients suggests partially divergent functional mechanisms underlying upper and lower limb disability.
P0605 - More dynamic functional network switching in cognitively declining multiple sclerosis patients (ID 777)
Abstract
Background
Cognitive impairment in multiple sclerosis (MS) is strongly related to functional network dysfunction. In the absence of MS, optimal cognitive functioning of an individual is ensured by dynamically adapting the configuration of the functional network as needed. How these dynamic patterns are altered in MS remains unclear.
Objectives
Our aim was to investigate the dynamic reconfiguration of cognitively relevant brain networks in MS, to identify specific brain network patterns related to progression of cognitive impairment.
Methods
Resting-state functional MRI (rs-fMRI) and cognitive scores were acquired from 230 patients with MS and 59 matched healthy controls, at baseline and at 5 year follow-up. Seven cognitive domains were examined with the expanded Brief Repeatable Battery of Neuropsychological tests. A sliding-window approach was used on the rs-fMRI data, for which brain regions were assigned to one of seven classic literature-based resting-state networks based on connectivity patterns at that point in time. How regions switched between networks was described using measures of promiscuity (number of networks switched to), flexibility (number of switches), cohesion (switches with another region), and disjointedness (independent switches). Linear mixed models were used for baseline and longitudinal analyses, controlling for age, sex, and education.
Results
At baseline, 42% of patients showed cognitive impairment (CI) (18% Mild CI, ≥2 tests Z<-1.5; 23% severe CI, ≥2 tests Z<-2) and 28% of patients declined over time (≥2 tests yearly reliable decline>0.25). At baseline, CI patients showed increased promiscuity, flexibility and cohesion (i.e. more switching between networks) compared to preserved patients. Patients displaying cognitive deterioration showed increases in cohesion over time. Higher baseline cohesion was related to less gray matter volume, and more white matter integrity loss and lesion volume. Within cognitive domains, cohesion was inversely related to verbal memory, information processing speed, and working memory.
Conclusions
In patients with MS, increased switching between brain networks was related to cognitive impairment and structural damage. Cohesion particularly increased over time in patients showing cognitive decline, indicating that switching together with other regions might be particularly more common. These results provide support for the hypothesis of a progressive destabilization of the functional brain network in MS.
P0615 - Physical disability is related to resting-state network atrophy and altered MEG-based functional network topology in multiple sclerosis. (ID 1350)
Abstract
Background
Clinical disability in multiple sclerosis (MS) is insufficiently explained by structural damage as measured with standard magnetic resonance imaging (MRI) measures. More advanced measures of brain network atrophy and functional network changes might better explain symptoms and clinical deterioration.
Objectives
To investigate the relevance of functional network alterations in addition to network atrophy for explaining physical disability in MS.
Methods
In this cross-sectional study 143 MS patients and 36 healthy control participants underwent resting-state magnetoencephalography (MEG) and structural MRI. Functional connectivity between regions was estimated using the phase lag index, from which the minimum spanning tree (MST) was constructed, representing the backbone of the functional network. The topology of the MST was described using the so-called tree hierarchy (MST-Th). Gray matter (GM) volume was calculated within literature-based resting-state network maps (i.e. visual, sensorimotor, dorsal attention, ventral attention, limbic, fronto-parietal, default mode, deep gray matter, and cerebellar networks). Physical disability was quantified with the Expanded Disability Status Scale (EDSS), Nine Hole Peg Test (9HPT) and Timed 25-Foot Walk Test (TWT). Network atrophy and topology were compared between groups and related to disability.
Results
Atrophy was apparent in all resting-state networks. All volumes correlated positively (p<.001) with EDSS and 9HPT: Spearman’s ρ between .289 and .567, highest correlations for sensorimotor, default mode, fronto-parietal and dorsal attention networks. EDSS correlated negatively with MST-Th in the lower alpha band (α1) (p < 0.008), while 9HPT correlated negatively with MST-Th in the upper and lower alpha, gamma, delta and theta bands (p <0.05), indicating a less efficient network relating to worse disability. TWT was related to atrophy in all networks, but not network topology. Together, MST-Th-α1, age, cerebellar and fronto-parietal atrophy explained 36% of EDSS variance, while 19% of 9HPT variance was explained by deep GM atrophy and MST-Th-α1. Lesion volume had no added significant effect on variance.
Conclusions
These results suggest that more advanced measures of network atrophy and functional network topology can explain a significant degree of disability variance in MS. In addition, mobility scores were not related to network changes, which could imply different underlying pathological substrates compared to those that underlie upper limb dexterity.
P0640 - Sensorimotor network dynamics predicts loss of upper and lower limb function in people with multiple sclerosis (ID 1048)
Abstract
Background
Both upper and lower limb disability is common in multiple sclerosis (MS), but do not always occur together, suggesting partially independent underlying mechanisms. Physical disability strongly relates to brain network disturbances in MS, yet network mechanisms underlying upper and lower disability progression remain unclear.
Objectives
To investigate the relationship between upper and lower limb progression and functional sensorimotor network changes in MS.
Methods
Longitudinal data was included from a prospectively acquired cohort, with baseline data collected between 2008 and 2012 and follow-up assessments between 2014 and 2017. Participants underwent MRI and dexterity (9-Hole Peg Test) and mobility (Timed 25-Foot Walk) tests at baseline and after 5 years. Patients were stratified into progressors (>20% decline) or non-progressors for both tests. Measures of network efficiency were calculated from resting-state functional MRI data using both static (i.e. calculated on the entire scan) and dynamic (i.e. fluctuations during the scan) approaches and compared between patient groups. Multiple logistic regression was used to identify independent predictors of upper and lower limb progression and baseline connectivity patterns.
Results
This study included 214 people with MS (age 47±11; 149 women) and 58 healthy controls (age 46±10; 31 women). Compared to respective non-progressors, upper limb progression (n=24) was related to higher dynamic efficiency of the right premotor cortex, somatosensory cortex and thalamus, while lower limb progression (n=37) was related to higher dynamic efficiency of the right supplementary motor area at baseline (p<0.05). Logistic regression showed that dynamic efficiency of the thalamus and supplementary motor area best predicted upper and lower limb progression respectively, independent of the severity of structural damage (p<0.01). Both areas displayed widespread higher dynamic connectivity in progressing compared to non-progressing patients at baseline (p<0.05).
Conclusions
Disability progression can be predicted by the severity of fluctuations (i.e. higher dynamics) in the efficiency of the sensorimotor network. The dynamic behavior of the thalamus and supplementary motor area were respectively related to upper and lower limb progression, possibly indicating different mechanisms underlying these types of progression in MS.
P0769 - Saccadic eye movements reflect functional connectivity of the oculomotor brain network in MS patients (ID 1108)
Abstract
Background
Eye movement is controlled by a widespread network of cortical and subcortical areas, the oculomotor brain network, thus accurate measurement of these movements could represent a non-invasive method to reflect (dys)functioning of these interconnected areas. This is especially relevant for diseases in which network disruption is known to represent a key pathological feature, as in multiple sclerosis (MS).
Objectives
To investigate the association between saccadic eye movements and functional connectivity of the oculomotor brain network in patients with MS.
Methods
Subjects were included from the prospective Amsterdam MS cohort. A validated standardized infrared oculography protocol (DEMoNS) was used for quantifying pro-saccades and anti-saccades (reflexive and voluntary saccadic eye movements, respectively). After resting-state magnetoencephalography (MEG) measurement, data pre-processing and beamforming of the MEG data to source space, 73 oculomotor regions of the Brainnetome atlas were included based on previous literature (i.e. the FOcuS atlas). The phase lag index (PLI) was used as a measure of functional connectivity (FC) between all regions within the oculomotor network (and it’s subnetworks) for the six conventional frequency bands. The relationship between saccadic parameters and mean FC was analyzed using multivariate linear regression models adjusted for sex, age and disease type. Effect size modification by sex was additionally investigated.
Results
The 183 included patients with MS showed altered saccadic eye movements compared to the 58 included healthy controls. Regarding pro-saccades, worse saccadic eye movement performance was mainly related to a higher FC in theta and gamma bands and a lower connectivity in alpha and beta bands. Strongest relations with FC were found for peak velocity and the parietal eye field (theta band, β -2.1 E-4, p=0.006), gain and the precuneus (gamma band, β -1.3 E-4, p=0.003) and gain and the inferior frontal eye field (theta band, β -21.0 E-4, p<0.001). For anti-saccades, the strongest associations were found between the proportion of errors and the thalamus (beta band, β 8.0 E-4, p=0.006) and error of the final eye position and the precuneus (theta band, β -6.2 E-4, p=0.004). For female MS patients the proportion of errors was also strongly related to the supplementary eye field (gamma band, β 6.4 E-4, p=0.003) and for male patients the latency of a correct response to the cingulate eye field (delta band, β 5.3 E-4, p=0.006).
Conclusions
Saccadic eye movements were related to altered functional connectivity of fronto-parietal brain regions and the thalamus in patients with MS. Furthermore, there was evidence for a relevant sex difference in patterns of functional damage of the oculomotor brain network. This network approach provides an additional backing for the future use of eye movement measurement as an easy applicable tool for monitoring or predicting the disease MS.