Nadine Akbar

Predicting employment status in multiple sclerosis patients: the utility of the MS functional composite

As many as two-thirds of multiple sclerosis (MS) patients are unable to retain employment. Neurological and cognitive status are known to be significant predictors of unemployment, but the relationship between the two is unclear. Furthermore, the association between employment status and depression, anxiety, and personality has not been adequately explored in MS patients. This study examined the demographic, neurological, neuropsychological, and personality factors associated with unemployment in MS. We also sought to determine the utility of the Multiple Sclerosis Functional Composite (MSFC), a measure of MS-related disability incorporating physical and cognitive measures, in predicting employment status. A consecutive sample of 106 MS patients (61.3% unemployed) completed the Brief Repeatable Battery of Neuropsychological Tests (BRBN), Hospital Anxiety and Depression Scale (HADS), and NEO Five-Factor Personality Inventory. The MSFC emerged as the most robust predictor of employment status in MS patients, exceeding the predictive value of the EDSS. Together with NEO “Agreeableness” and HADS Depression subscore, the MSFC accounted for 49.8% of the variance in employment status. Unemployment was also associated with a progressive disease course, longer disease duration, and being female. While Global Cognitive Impairment did not differentiate between groups, unemployed patients scored significantly lower on three of five BRBN indices: Symbol Digit Modality Test, Paced Auditory Serial Addition Test, and Word List Generation. The findings highlight the utility of the MSFC as a predictor of unemployment in MS. Furthermore, a strong association was found between unemployment and the personality construct “Agreeableness”, and severity of depression.

The perceptual consequences of the attentional bias: evidence for distractor removal

A fundamental question of attentional research concerns the perceptual consequences of attention. Spatial attention can enhance stimuli within the focus of attention relative to stimuli outside; or attention can remove the influence of distracting stimuli and other forms of external noise inside the focus of attention. It is known that both strategies apply depending on how attention is cued to a location in space. Here we asked which strategy applies in an uncued situation in which people show a spontaneous bias of attention to the left side. To measure bias, we used a gratingscales task with stimuli corrupted by pixel noise. If biased attention resulted in biased stimulus enhancement its effect should be largest when there is little noise or few distractors within the attended region, and bias should decline with increasing noise. If, however, bias caused distractors to be removed asymmetrically, larger bias should show up with noisy stimuli. We found that bias rose exponentially as noise increased, in agreement with the external noise removal model, and we found evidence that noise modified interhemispheric competition between attentional systems. Our data offer new insights into the neural mechanisms of the right-hemisphere dominance in spatial and attentional tasks.

Validity of an Internet version of the Multiple Sclerosis Neuropsychological Questionnaire

Background: Neuropsychological batteries are long and require expertise to administer. For this reason, the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) was developed as it is quick and easy to complete. The informant version of the scale has proven to be a useful screen for cognitive impairment in multiple sclerosis (MS). Objective: The objective was to validate an Internet version of the MSNQ. Methods: The following psychometric data were collected at home over the Internet in 82 MS patients: (a) patient self-report version MSNQ (P-MSNQ), (b) informant version MSNQ (I-MSNQ), and (c) Center for Epidemiological Studies Depression Scale (CES-D). Thereafter patients underwent in-office testing with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). The sensitivity and specificity of the Internet MSNQ to detect cognitive impairment relative to the BRB-N was determined using receiver operating characteristic (ROC) curve analysis. Results: Thirty-five percent of the sample was cognitively impaired. The P-MSNQ was correlated with depression and two tests of the BRB-N. The I-MSNQ was correlated with depression and all five tests of the BRB-N. A cut-off score of 26 on the I-MSNQ gave a sensitivity and specificity of 72% and 60% respectively. Test-retest and internal reliability analyses were strong for both the P-MSNQ and I-MSNQ. Conclusion: This is the first attempt at an Internet validation of the MSNQ. The modest sensitivity and specificity values suggest that further research is needed before either the patient or informant version of the MSNQ can be used for neuropsychological screening purposes over the Internet.

Alterations in Functional and Structural Connectivity in Pediatric-Onset Multiple Sclerosis

Background Reduced white matter (WM) integrity is a fundamental aspect of pediatric multiple sclerosis (MS), though relations to resting-state functional MRI (fMRI) connectivity remain unknown. The objective of this study was to relate diffusion-tensor imaging (DTI) measures of WM microstructural integrity to resting-state network (RSN) functional connectivity in pediatric-onset MS to test the hypothesis that abnormalities in RSN reflects changes in structural integrity. Methods This study enrolled 19 patients with pediatric-onset MS (mean age = 19, range 13–24 years, 14 female, mean disease duration = 65 months, mean age of disease onset = 13 years) and 16 age- and sex-matched healthy controls (HC). All subjects underwent 3.0T anatomical and functional MRI which included DTI and resting-state acquisitions. DTI processing was performed using Tract-Based Spatial Statistics (TBSS). RSNs were identified using Independent Components Analysis, and a dual regression technique was used to detect between-group differences in the functional connectivity of RSNs. Correlations were investigated between DTI measures and RSN connectivity. Results Lower fractional anisotropy (FA) was observed in the pediatric-onset MS group compared to HC group within the entire WM skeleton, and particularly the corpus callosum, posterior thalamic radiation, corona radiata and sagittal stratum (all p < .01, corrected). Relative to HCs, MS patients showed higher functional connectivity involving the anterior cingulate cortex and right precuneus of the default-mode network, as well as involving the anterior cingulate cortex and left middle frontal gyrus of the frontoparietal network (all p < .005 uncorrected, k≥30 voxels). Higher functional connectivity of the right precuneus within the default-mode network was associated with lower FA of the entire WM skeleton (r = -.525, p = .02), genu of the corpus callosum (r = -.553, p = .014), and left (r = -.467, p = .044) and right (r = -.615, p = .005) sagittal stratum. Conclusions Loss of WM microstructural integrity is associated with increased resting-state functional connectivity in pediatric MS, which may reflect a diffuse and potentially compensatory activation early in MS.

Altered resting-state functional connectivity in cognitively preserved pediatric-onset MS patients and relationship to structural damage and cognitive performance

Objective: To evaluate resting-state functional connectivity (FC) and relationship to brain volumes and cognition in a sample of cognitively preserved pediatric-onset multiple sclerosis (MS) patients. Methods: Sixteen cognitively intact pediatric-onset MS patients and 15 healthy age- and sex-matched controls underwent cognitive testing and 3T anatomical and functional MRI. Resting-state FC patterns were examined using region-of-interest-based timeseries correlations. Results: Compared to controls, pediatric-onset MS patients demonstrated higher FC of the precuneus, particularly with the anterior cingulate cortex (z=4.21, p<.001), frontal medial cortex (z=3.48, p<.001), and cerebellum (z=3.72, p<.001). Greater T2 lesion volume and lower normalized thalamic volume were associated with reduced FC of the thalamus, especially for FC with the right superior occipital region (t=−2.87, p=.0123 and t=2.27, p=.04 respectively). FC of the left frontal medial cortex was negatively correlated with composite cognitive z-score in the pediatric-onset MS group (p<.05). Conclusions: Greater resting-state FC between posterior and anterior brain regions is present in pediatric-onset MS. With greater disease-related structural pathology, there is a disruption of thalamo-cortical FC. In the absence of actual cognitive impairment, heightened FC of the frontal medial cortex was associated with lower cognitive performance, suggesting that greater functional resources are recruited during resting-state in patients with reduced cognitive efficiency.

Brain activation patterns and cognitive processing speed in patients with pediatric-onset multiple sclerosis

ABSTRACT Objective: This study aimed to determine the extent and pattern of brain activation elicited by a functional magnetic resonance imaging version of the Symbol Digit Modalities Test (fMRI–SDMT), a task of information processing speed, in pediatric-onset multiple sclerosis (MS) patients as compared to sex- and age-matched non-MS self-reported healthy individuals. Method: Participants included 20 right-handed individuals aged 13–24 years with pediatric-onset MS (mean age = 19 years, 15 female) and 16 non-MS self-reported healthy individuals. All participants underwent a 3.0-tesla MRI scan with structural (T1; T2; proton density, PD; fluid-attenuated inversion recovery, FLAIR) and fMRI–SDMT acquisition. Participants were instructed to indicate with a button press whether a single pairing of a symbol to a number matched any of those shown in a key that displays nine possible pairings. Results: Response time (p = .909) and accuracy (p = .832) on the fMRI–SDMT did not differ between groups. However, the MS group demonstrated lower overall activation than the non-MS group in the right middle frontal gyrus (p = .003). Within the MS group, faster response time was associated with greater activation of the right inferior occipital, anterior cingulate, right superior parietal, thalamus, and left superior occipital cortices (all p < .05). A significant interaction effect was demonstrated, indicating that faster response time was associated with greater activation of the left superior occipital region in the pediatric MS group than in the non-MS group (p = .002). Conclusions: Attenuated activation of frontal regions was observed in this cohort of pediatric-onset MS patients when performing the fMRI–SDMT, even in the absence of behaviorally detectable deficits. Within the MS group only, faster response time elicited greater activation, suggesting this to be an adaptive mechanism that may contribute to limiting the impact of disease-related structural pathology.

The Experience of Persons With Multiple Sclerosis Using MS INFoRm: An Interactive Fatigue Management Resource

We aimed to understand participants’ experiences with a self-guided fatigue management resource, Multiple Sclerosis: An Interactive Fatigue Management Resource (MS INFoRm), and the extent to which they found its contents relevant and useful to their daily lives. We recruited 35 persons with MS experiencing mild to moderate fatigue, provided them with MS INFoRm, and then conducted semistructured interviews 3 weeks and 3 months after they received the resource. Interpretive description guided the analysis process. Findings indicate that participants’ experience of using MS INFoRm could be understood as a process of change, influenced by their initial reactions to the resource. They reported experiencing a shift in knowledge, expectations, and behaviors with respect to fatigue self-management. These shifts led to multiple positive outcomes, including increased levels of self-confidence and improved quality of life. These findings suggest that MS INFoRm may have a place in the continuum of fatigue management interventions for people with MS.

Progressive resistance exercise training and changes in resting-state functional connectivity of the caudate in persons with multiple sclerosis and severe fatigue: A proof-of-concept study

ABSTRACT Fatigue is one of the most disabling symptoms of multiple sclerosis (MS). While progressive resistance training (PRT) has been shown to reduce fatigue in persons with MS, it is not clear why these reductions occur. One hypothesis is that PRT may induce functional changes to the caudate, a region highly implicated in MS fatigue. The aim of the current study was to study the effects of PRT on overall fatigue impact and resting-state functional connectivity of the caudate in persons with MS reporting severe fatigue. Participants were semi-randomly assigned to either a 16-week home-based PRT (n = 5) or stretching control (n = 5) condition. Both groups demonstrated reductions in overall fatigue impact (main effect of time: F = .84, d = .65). Significant group × time interactions were found, with the PRT group demonstrating post-training increases in functional connectivity between the caudate and left inferior parietal (F = 66.0, p < .001), bilateral frontal (both p < .001), and right insula (F = 21.8, p = .002) regions compared to the stretching group. Furthermore, greater post-training increases in functional connectivity between the caudate and left inferior parietal region were associated with greater decreases in cognitive fatigue (r = −.52) specifically. This study provides initial evidence for the caudate as a potential neural substrate for the beneficial effects of PRT on fatigue in persons with MS.

Imaging Pediatric Multiple Sclerosis—Challenges and Recent Advances

Abstract Pediatric onset multiple sclerosis (POMS) is a rare disease with an incidence of 0.07 to 2.9/100′000 children per year. It follows a relapsing‐remitting disease course and is characterized by rapid accrual of inflammatory lesions, high relapse frequency, and early cognitive impairment. Magnetic resonance imaging (MRI) plays a pivotal role in the diagnosis of POMS, and in the exclusion of other disorders mimicking POMS. Furthermore, MRI aids in disease monitoring, and in the evaluation of therapeutic efficacy in both clinical practice and clinical trials. Volumetric MRI studies, diffusion tensor imaging, resting‐state, and task‐based functional MRI provide deeper insight into the impact of POMS on maturing neural networks. This review article aims to highlight the importance of MRI in the care of POMS patients and to provide an overview on the different MRI techniques used in the management of POMS.

Maturational Trajectory of Processing Speed Performance in Pediatric Multiple Sclerosis

ABSTRACT Processing speed is a frequently affected cognitive domain in pediatric multiple sclerosis (MS) and is commonly assessed using the Symbol Digit Modalities Test (SDMT). The objective of this study was to determine maturational trajectories in SDMT performance and baseline factors affecting trajectories in a sample of 82 pediatric MS individuals. Performance on the SDMT increased with age in patients with pediatric MS followed by a subsequent decline. Furthermore, patients who were older at disease onset and had a higher IQ showed greater gains with age, suggesting that these factors may be protective with respect to cognitive maturation in pediatric MS.