Relation between EEG and disability scores in multiple sclerosis

A disability-scoring and an EEG-spectral analysis was performed in patients suffering from clinically and biochemically (oligoclonal aspect in cerebro-spinal fluid) proven multiple sclerosis at two stages of their illness, that are before and after a short intensive immuno suppressive therapy. In both stages a relationship is found between the degree of disability and the amount of beta activity in the fronto-central area and the amount of the theta activity in the temporal area. Significant improvement in the clinical state of the patient and a marked increase of the mean alpha frequency in the parietooccipital region could be demonstrated after short intensive immunosuppressive therapy.     

Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis

Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting‐state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting‐state fMRI, T1‐weighted and T2‐weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease‐related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting‐state fMRI, T1‐weighted, T2‐weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262–4275, 2016. © 2016 Wiley Periodicals, Inc.     

Intranetwork and internetwork functional connectivity abnormalities in pediatric multiple sclerosis

Active motor functional magnetic resonance imaging (fMRI) studies have shown that pediatric multiple sclerosis (MS) patients have a strictly lateralized pattern of activations and a preserved functional connectivity (FC) within the motor system when compared to age‐matched healthy controls. However, it is still not clear whether a preserved FC in pediatric MS is present only in the motor system, or involves other relevant functional system. Resting‐state (RS) fMRI is a valuable tool for an unbiased investigation of FC abnormalities of multiple networks. This study explored abnormalities of RS FC within and between large‐scale neuronal networks from 44 pediatric MS patients and 27 controls and their correlation with clinical, neuropsychological, and conventional MRI measures. Compared to controls, pediatric MS patients had a decreased FC of several regions of the sensorimotor, secondary visual, default‐mode (DMN), executive control, and bilateral working memory (WMN) networks. They also experienced an increased FC in the right medial frontal gyrus of the attention network, which was correlated with T2 lesion volume. Cognitively impaired patients had decreased RS FC of the right precuneus of the left WMN. An increased FC between the sensorimotor network and the DMN, and between the L WMN and the attention network as well as a decreased FC between L WMN and the DMN were also found. A distributed pattern of FC abnormalities within large‐scale neuronal networks occurs in pediatric MS patients, contributes to their cognitive status, and is partially driven by focal white matter lesions. Internetwork connectivity is relatively preserved in these patients. Hum Brain Mapp 35:4180–4192, 2014. © 2014 Wiley Periodicals, Inc .     

Preserved network functional connectivity underlies cognitive reserve in multiple sclerosis

Cognitive reserve is one's mental resilience or resistance to the effects of structural brain damage. Reserve effects are well established in people with multiple sclerosis (PwMS) and Alzheimer's disease, but the neural basis of this phenomenon is unclear. We aimed to investigate whether preservation of functional connectivity explains cognitive reserve. Seventy‐four PwMS and 29 HCs underwent neuropsychological assessment and 3 T MRI. Structural damage measures included gray matter (GM) atrophy and network white matter (WM) tract disruption between pairs of GM regions. Resting‐state functional connectivity was also assessed. PwMS exhibited significantly impaired cognitive processing speed (t = 2.14, p = .037) and visual/spatial memory (t = 2.72, p = .008), and had significantly greater variance in functional connectivity relative to HCs within relevant networks (p < .001, p < .001, p = .016). Higher premorbid verbal intelligence, a proxy for cognitive reserve, predicted relative preservation of functional connectivity despite accumulation of GM atrophy (standardized‐β = .301, p = .021). Furthermore, preservation of functional connectivity attenuated the impact of structural network WM tract disruption on cognition (β = ?.513, p = .001, for cognitive processing speed; β = ?.209, p = .066, for visual/spatial memory). The data suggests that preserved functional connectivity explains cognitive reserve in PwMS, helping to maintain cognitive capacity despite structural damage.     

Physical activity associated with increased resting-state functional connectivity in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, resulting in physical, cognitive and affective disturbances, with notable declines in the ability to learn and retain new information. In this study, we examined if higher levels of physical activity in MS individuals were associated with an increased resting-state connectivity of the hippocampus and cortex, resulting in better performance on a task of episodic memory. Forty-five individuals with a clinically definite diagnosis of MS were recruited for the study. Consistent with previous reports, hippocampus was functionally connected to the posteromedial cortex, parahippocampal gyrus, superior frontal gyrus, and the medial frontal cortex. Higher levels of physical activity in MS patients were associated with an increased coherence between the hippocampus and the posteromedial cortex (PMC). The increased connectivity between these two regions, in turn, was predictive of better relational memory, such that MS patients who showed an increased coherence between the left (not right) hippocampus and the PMC also showed better relational memory. Results of the study are interpreted in light of the challenge of disentangling effects of physical activity from effects of disease severity and its neuropathological correlates.     

Age-related disability in multiple sclerosis

There is evidence that the clinical course of multiple sclerosis is age related. The present study evaluated the relationship between age and rate of disability progression in a large hospital-based cohort of definite cases of multiple sclerosis (n= 1,463). Patients were followed every 6 to 12 months for a total period of observation of 11,387.8 person-years. Expanded Disability Status Scale scores increased significantly with increasing current age and longer duration of disease (p=0.007). Median times to reach Expanded Disability Status Scale scores of 4.0 and 6.0, assessed using an extended Kaplan-Meier method with age as a categorical time-varying covariate, were significantly longer among patients aged 20 to 35 years compared with patients aged 36 to 50 and 51 to 65 years (p < 0.0001). Significant associations were observed between mean Expanded Disability Status Scale scores and age at disease onset, current age, and the interaction of age at disease onset and current age (p < 0.001). Current age had a greater effect (59% of variability in the model) on disease severity than did age at disease onset. Furthermore, a multiplicative effect on Expanded Disability Status Scale score was observed for age at disease onset and current age combined, indicating a faster rate of disease progression in older patients. In conclusion, the results of the current study demonstrate the impact of age on rate of disability progression in multiple sclerosis and suggest that an age-adjusted progression index may be a more relevant criterion for defining differences between multiple sclerosis groups.     

Correlation between structural and functional connectivity impairment in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterized by progressive loss of motor function. While the pathogenesis of ALS remains largely unknown, imaging studies of the brain should lead to more insight into structural and functional disease effects on the brain network, which may provide valuable information on the underlying disease process. This study investigates the correlation between changes in structural connectivity (SC) and functional connectivity (FC) of the brain network in ALS. Structural reconstructions of the brain network, derived from diffusion weighted imaging (DWI), were obtained from 64 patients and 27 healthy controls. Functional interactions between brain regions were derived from resting‐state fMRI. Our results show that (i) the most structurally affected connections considerably overlap with the most functionally impaired connections, (ii) direct connections of the motor cortex are both structurally and functionally more affected than connections at greater topological distance from the motor cortex, and (iii) there is a strong positive correlation between changes in SC and FC averaged per brain region (r = 0.44, P < 0.0001). Our findings indicate that structural and functional network degeneration in ALS is coupled, suggesting the pathogenic process affects both SC and FC of the brain, with the most prominent effects in SC. Hum Brain Mapp 35:4386–4395, 2014. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Resting-state functional connectivity in multiple sclerosis: An examination of group differences and individual differences

Multiple sclerosis (MS) is a neurodegenerative, inflammatory disease of the central nervous system, resulting in physical and cognitive disturbances. The goal of the current study was to examine the association between network integrity and composite measures of cognition and disease severity in individuals with relapsing-remitting MS (RRMS), relative to healthy controls. All participants underwent a neuropsychological and neuroimaging session, where resting-state data was collected. Independent component analysis and dual regression were employed to examine network integrity in individuals with MS, relative to healthy controls. The MS sample exhibited less connectivity in the motor and visual networks, relative to healthy controls, after controlling for group differences in gray matter volume. However, no alterations were observed in the frontoparietal, executive control, or default-mode networks, despite previous evidence of altered neuronal patterns during tasks of exogenous processing. Whole-brain, voxel-wise regression analyses with disease severity and processing speed composites were also performed to elucidate the brain–behavior relationship with neuronal network integrity. Individuals with higher levels of disease severity demonstrated reduced intra-network connectivity of the motor network, and the executive control network, while higher disease burden was associated with greater inter-network connectivity between the medial visual network and areas involved in visuomotor learning. Our findings underscore the importance of examining resting-state oscillations in this population, both as a biomarker of disease progression and a potential target for therapeutic intervention.     

Increased functional connectivity within memory networks following memory rehabilitation in multiple sclerosis

Identifying effective behavioral treatments to improve memory in persons with learning and memory impairment is a primary goal for neurorehabilitation researchers. Memory deficits are the most common cognitive symptom in multiple sclerosis (MS), and hold negative professional and personal consequences for people who are often in the prime of their lives when diagnosed. A 10-session behavioral treatment, the modified Story Memory Technique (mSMT), was studied in a randomized, placebo-controlled clinical trial. Behavioral improvements and increased fMRI activation were shown after treatment. Here, connectivity within the neural networks underlying memory function was examined with resting-state functional connectivity (RSFC) in a subset of participants from the clinical trial. We hypothesized that the treatment would result in increased integrity of connections within two primary memory networks of the brain, the hippocampal memory network, and the default network (DN). Seeds were placed in left and right hippocampus, and the posterior cingulate cortex. Increased connectivity was found between left hippocampus and cortical regions specifically involved in memory for visual imagery, as well as among critical hubs of the DN. These results represent the first evidence for efficacy of a behavioral intervention to impact the integrity of neural networks subserving memory functions in persons with MS.     

Multiple sclerosis: Mechanisms of disability accumulation in multiple sclerosis

Natural history studies have identified numerous features of disability progression in patients with multiple sclerosis (MS), and have provided valuable insight into the underlying pathology of the disease that could assist the development of new treatment strategies. A new study indicates that disability progression occurs in two stages in patients with MS.     

A multidimensional assessment of multiple sclerosis: relationships between disability domains

OBJECTIVE: To test the feasibility of a multidimensional assessment based on both task-related and self-evaluation questionnaire scores in patients with multiple sclerosis (MS); ii) to correlate the results from selective measures with the severity of illness in terms of the Expanded Disability Status Scale (EDSS) score; iii) to assess the relationships between different domains of MS-related disability and handicap. PATIENTS AND METHODS: Eighty-three MS patients (M/F 31/52; age 43.26 +/- 10.9 years, range 21-72) underwent a standard clinical evaluation of motor abilities (by means of the Rivermead Mobility index, Timed Walking Test, Nine Hole Peg test and Hauser Ambulation Index) and cognitive performances (using Digit Symbol, Buschke-Fuld selective remind test, "FAS"-Word Fluency, Wisconsin Card Sorting test and Block design test). The Beck Depression inventory, MS Specific Fatigue Scale, Functional Assessment of MS and London Handicap Scale were applied to evaluate mood, fatigue, quality of life and handicap, respectively. Minimal Record of Disability measures - MRD (i.e. EDSS, Inability Status Scale and Environmental Status Scale) were also applied to test the criterion validity of the selected disability and handicap scales. The Kruskal-Wallis H-test for independent samples tested differences between subgroups with an increasing EDSS score (<3.5, 3.5-6.0, >6.0). The covariance and redundancy of measures included in the multidimensional assessment were evaluated through Factor Analysis. The Multiple Regression Analysis was used to detect the relative impact of either motor or cognitive disabilities and depression on handicap and quality of life. RESULTS: The multimodal assessment took 70 min on average to be performed, being well accepted by patients. Motor abilities worsened as the EDSS score rose, unlike cognitive performances which proved to be similarly impaired at different severity levels. Measures of fatigue and depression were not related to EDSS values. The chosen measures were assigned by Factor Analysis to 4 domains corresponding to motor performance, executive performance, cognitive abilities and quality of life, respectively. Regression analysis showed how handicap and depression independently affect quality of life. While the handicap score is mostly influenced by motor ability, as measured by the Rivermead Mobility Index, the depression score grows independently of any physical or cognitive disability and seems to be related to fatigue self-assessment scores. CONCLUSIONS: A multidimensional approach to MS patient assessment allows a more detailed and sensitive evaluation of their disability profile and perceived difficulties, leading to a care programme tailored to the patient's needs.     

The relationship between disability and memory dysfunction in multiple sclerosis.

We examined the relationship between memory impairment and functional disability in multiple sclerosis. Tests of memory, sensorimotor ability, and functional capacity were administered to fifty-six subjects with chronic-progressive or remitting-relapsing MS. Sensorimotor impairment, functional disability, and chronicity predicted impairment on various measures of memory acquisition, while age and type of diagnosis did not. After accounting for the effects of initial acquisition, delayed-recall performance was weakly-associated with disability. We suggest that: (1) Functional disability is associated with memory loss in MS; (2) MS-forgetting is caused by defective acquisition, rather by a deficit in consolidation or storage; (3) Level of disease activity, rather than type of MS diagnosis, determines the degree of memory impairment; and (4) MS disability needs to be evaluated multidimensionally, to account for both neurologic and functional impairment.     

The association between cognitive impairment and physical disability in multiple sclerosis

BACKGROUND: The association between cognitive impairment and physical disability was examined in a larger, more representative sample of patients with multiple sclerosis (MS) than in previous studies. METHOD: Two hundred and fifty-three patients attending an MS clinic were assessed with respect to physical disability using the Expanded Disability Status Scale and cognitive impairment using a battery of neuropsychological tests. RESULTS: Physical disability correlated with duration of disease; cognitive impairment did not. Virtually all measures derived from the cognitive battery were significantly correlated with physical disability. Three measures of speeded information processing and one involving delayed recall of verbal material were unique predictors of disability status. The relationship between cognitive impairment and physical disability was equivalent for patients with shorter (< 3 years) versus longer (> 10 years) disease duration. Cognitive impairment correlated with the rate of disability progression as reflected by the progression index. CONCLUSION: Cognitive impairment is more closely associated with physical disability than most previous studies indicate. This relationship appears to be stable throughout the duration of MS, although this conclusion is qualified by the cross-sectional design of the study. Further attention should be paid to cognitive impairment as a possible predictor of the rate of patients' physical decline.     

Mastery,functional disability and perceived health status in patients with multiple sclerosis

Background and purpose: Multiple sclerosis (MS) is a chronic disease that is difficult to predict and to cope with. Mastery refers to the extent to which patients see themselves as being in control of the forces that affect their lives. It may play an important role in perceived health status and well‐being. The purpose of this study was to clarify whether mastery is associated with functional disability and perceived health status in MS patients and how such an association might function. Methods: Two hundred and three MS patients completed the Short‐Form‐36 Health Survey as well as the Pearlin–Schooler Mastery Scale. Functional disability was assessed using the Kurtzke Expanded Disability Status Scale. Hierarchical multiple linear regression analyses were performed on the data from two MS age groups: <45 and ≥45 years of age. Results: Functional disability was negatively associated with perceived physical health status in both age groups and with perceived mental health status in younger age group. Mastery was positively associated with perceived health status in older age group. Discussion: The findings confirm that mastery might be helpful for older MS patients. Education strategies for MS patients aimed at personal empowerment for the maintaining of physical and mental well‐being may be important.     

Relation between functional brain imaging, cognitive impairment and cognitive rehabilitation in patients with multiple sclerosis

Cognitive impairment belongs to the core symptoms in MS affecting quality of life, self-esteem, and social as well as occupational functioning. Due to this high impact on patients' well-being efficient treatment concepts are required. Imaging studies on cognition have shown that functional reorganisation takes place spontaneously to compensate for deficits. In mildly to moderately impaired patients these processes may support coping with emerging deficits. However, these compensatory processes seem to be limited as brain activation of cognitively severely impaired patients is characterised by decreased additional recruitment of brain regions. Cognitive rehabilitation concentrates on the question whether induction of brain plasticity is possible for both the support of the spontaneous processes and the initiation of new ones. Combining cognition, brain imaging and cognitive rehabilitation in MS, an intriguing question is whether fMRI can provide further insights into the mechanisms of induced plasticity and serve as objective outcome measures for efficient cognitive intervention.     

Relation between functional brain imaging,cognitive impairment and cognitive rehabilitation in patients with multiple sclerosis

Journal of Neurology - Cognitive impairment belongs to the core symptoms in MS affecting quality of life, self-esteem, and social as well as occupational functioning. Due to this high impact on...     

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.