Neural correlates of effort-dependent and effort-independent cognitive fatigue components in patients with multiple sclerosis.

BACKGROUND: Among patients with multiple sclerosis (MS), fatigue is the most commonly reported symptom. It can be subdivided into an effort-dependent (fatigability) and an effort-independent component (trait-fatigue). OBJECTIVE: The objective was to disentangle activity changes associated with effort-independent "trait-fatigue" from those associated with effort-dependent fatigability in MS patients. METHODS: This study employed behavioral measures and functional magnetic imaging to investigate neural changes in MS patients associated with fatigue. A total of 40 MS patients and 22 age-matched healthy controls performed in a fatigue-inducing N-back task. Effort-independent fatigue was assessed using the Fatigue Scale of Motor and Cognition (FSMC) questionnaire. RESULTS: Effort-independent fatigue was observed to be reflected by activity increases in fronto-striatal-subcortical networks primarily involved in the maintenance of homeostatic processes and in motor and cognitive control. Effort-dependent fatigue (fatigability) leads to activity decreases in attention-related cortical and subcortical networks. CONCLUSION: These results indicate that effort-independent (fatigue) and effort-dependent fatigue (fatigability) in MS patients have functionally related but fundamentally different neural correlates. Fatigue in MS as a general phenomenon is reflected by complex interactions of activity increases in control networks (effort-independent component) and activity reductions in executive networks (effort-dependent component) of brain areas.

Meta-Synthesis of Qualitative Research on Facilitators and Barriers of Return to Work After Stroke.

Purpose Despite existing rehabilitation services, return to work (RTW) rates among stroke survivors are quite low. An increased number of qualitative studies have been conducted to identify facilitators and barriers to RTW after stroke and to derive recommendations for future interventions. The aim of our study was to carry out a meta-synthesis of those studies and thus strengthen evidence in the field. Methods To identify relevant studies (qualitative studies focusing on RTW after stroke, published in English or German between 2000 and 2015), we conducted a systematic literature search in PubMed, OVID, and Web of Science. After assessing the quality of eligible studies, we synthesized their findings according to meta-ethnographic methodology. Results Fourteen out of 553 studies-three of very high, seven of high, three of medium, and one of low quality-met the inclusion criteria. After the extraction of all first-order concepts and their translation into 64 second-order interpretations, we synthesized the findings by developing a model of RTW factors after stroke. It contains factors related to the person (impairments, coping/adaptation, significance of work/RTW motivation), workplace (job demands/work adaptations, disability management, work climate/social support), and rehabilitation services (availability, accessibility, appropriateness), as well as relevant factors in the interaction of these three stakeholders (work capacity, performance and capability, and initial RTW experiences). Three basic principles-adaptiveness, purposefulness, and cooperativeness-complete the model and led us to its name: the APC model. Conclusions Successful RTW after stroke depends on diverse factors and stakeholders. Rehabilitation strategies have to consider this; otherwise they become RTW barriers themselves.

Fatigue in Multiple Sclerosis Compared to Stroke.

OBJECTIVES: Fatigue is typically associated with multiple sclerosis (MS), but recent studies suggest that it is also a problem for patients with stroke. While a direct comparison of fatigue in, e.g., Stroke and MS is desirable, it is presently not easily possible because of different definitions and assessment tools used for the two conditions. In the present study, we therefore assessed fatigue in Stroke and MS using a generic, not disease-specific instrument to allow transdiagnostic comparison. METHOD: A total of 137 patients with MS and 102 patients with chronic stroke completed the SF-36, a generic questionnaire assessing health related quality of life. Fatigue was measured through the vitality scale of the SF-36. The vitality scale consists of two positive items ("lot of energy," "full of life") and two negative ones ("worn out," "tired"). The two negative ones were scaled in reverse order. The vitality scale has been recommended as reciprocal index of fatigue. RESULTS: Normalized vitality scores in MS (35.3) and stroke (42.1) were clearly lower than published reference values from the SF-36 in age-matched healthy controls. The sum score of the vitality items was lower in MS than in stroke patients. This difference could not be explained by age, gender, or the Physical Functioning Scale of the SF-36. Both patient groups showed no positive correlation between fatigue and physical functioning. Fatigue - as determined with the vitality scale of the SF-36 - correlated with the estimated working capacity in MS patients, but not in stroke patients. CONCLUSION: These findings confirm high fatigue in MS and stroke patients with higher values in MS. Fatigue has a higher impact on working capacity in MS than in stroke. Fatigue in both patient groups is not a direct consequent of physical functioning/impairment. Vitality score of the SF-36 is a suitable transdiagnostic measure for the assessment of fatigue in stroke and MS.

Patterns of linguistic and numerical performance in aphasia.

BACKGROUND: Empirical research on the relationship between linguistic and numerical processing revealed inconsistent results for different levels of cognitive processing (e.g., lexical, semantic) as well as different stimulus materials (e.g., Arabic digits, number words, letters, non-number words). Information of dissociation patterns in aphasic patients was used in order to investigate the dissociability of linguistic and numerical processes. The aim of the present prospective study was a comprehensive, specific, and systematic investigation of relationships between linguistic and numerical processing, considering the impact of asemantic vs. semantic processing and the type of material employed (numbers compared to letters vs. words). METHODS: A sample of aphasic patients (n = 60) was assessed with a battery of linguistic and numerical tasks directly comparable for their cognitive processing levels (e.g., perceptual, morpho-lexical, semantic). RESULTS AND CONCLUSIONS: Mean performance differences and frequencies of (complementary) dissociations in individual patients revealed the most prominent numerical advantage for asemantic tasks when comparing the processing of numbers vs. letters, whereas the least numerical advantage was found for semantic tasks when comparing the processing of numbers vs. words. Different patient subgroups showing differential dissociation patterns were further analysed and discussed. A comprehensive model of linguistic and numerical processing should take these findings into account.

Neural correlates of training-induced improvements of calculation skills in patients with brain lesions.

PURPOSE: The loss of calculation skills due to brain lesions leads to a major reduction in the quality of life and is often associated with difficulties of returning to work and a normal life. Very little is known about the neural mechanisms underlying performance improvement due to calculation training during rehabilitation. The current study investigates the neural basis of training-induced changes in patients with acalculia following ischemic stroke or traumatic brain lesions. METHODS: Functional hemodynamic responses (fMRI) were recorded in seven patients during calculation and perceptual tasks both before and after acalculia training. RESULTS: Despite the heterogeneity of brain lesions associated with acalculia in our patient sample, a common pattern of training-induced changes emerged. Performance improvements were associated with widespread deactivations in the prefrontal cortex. These deactivations were calculation-specific and only observed in patients exhibiting a considerable improvement after training. CONCLUSION: These findings suggest that the training-induced changes in our patients rely on an increase of frontal processing efficiency.

Modulation of alertness by sustained cognitive demand in MS as surrogate measure of fatigue and fatigability.

OBJECTIVE: This study used reaction time (RT) as an objective marker of cognitive fatigue and fatigability in patients with multiple sclerosis (MS). METHOD: RT was measured in fifteen healthy controls and in thirty MS patients with cognitive fatigue identified with the Fatigue Scale for Motor and Cognitive Function (FSMC). Secondary fatigue was excluded through the Epworth Sleepiness Scale and the Beck Depression Inventory. RT was measured at rest (t1), following a 2.5 hour test session inducing high cognitive load (t2), and a one hour recovery period (t3). RESULTS: At rest mean RT was longer in patients than in controls (391 ms vs 205 ms). After exerting cognitive load (t2), RT in patients increased dramatically but remained unchanged in controls. After the recovery period (t3), RT returned to baseline levels in most patients. Patients further showed a significant correlation between RT and FMSC scores at t1, t2 and t3. CONCLUSION: RT performance is a suitable surrogate marker for assessing fatigue. RT is sensitive to cognitive load and the recovery from cognitive demand. It hence represents an objective index for fatigability which can inform the management and treatment of MS.

Induction of cognitive fatigue in MS patients through cognitive and physical load.

The objective of the study was to investigate whether cognitive fatigue in patients with multiple sclerosis (MS) is a spontaneous phenomenon or whether it can be provoked or exacerbated through cognitive effort and motor exercise. Thirty two patients with definite MS and cognitive fatigue according to the Fatigue Scale for Motor and Cognitive Functions (FSMC ≥ 22) performed attention tests (alertness, selective, and divided attention subtests from the TAP test battery for attention performance) twice during rest (baseline), and before and after treadmill training and cognitive load (a standardised battery of neuropsychological tests lasting 2.5 hours). Subjective exhaustion was assessed with a 10-point rating scale. Tonic alertness turned out to be the most sensitive test and showed significantly increased reaction times after treadmill training and after cognitive load. Patients' subjective assessment of exhaustion (10-point rating scale) and the objective test results were discrepant. In contrast, healthy control subjects (N = 20) did not show any decline of performance in the subtest alertness after cognitive or physical load. Data favour the concept that fatigue is induced by physical and mental load. Discrepancies between subjective and objective assessment offer therapeutic options. The common notion of a purely "subjective" lack of physical and/or mental energy should be reconsidered.

Fatigue-related diurnal variations of cognitive performance in multiple sclerosis and stroke patients.

OBJECTIVE: Cognitive impairment is a common symptom of multiple sclerosis (MS). The present study aimed to assess fatigue-related diurnal variations of cognitive performance in MS patients. METHOD: Subjective cognitive fatigue and cognitive performance in three reaction time tasks differing in cognitive demands (alertness, Go/NoGo, divided attention) was measured at three different times of day on two consecutive days for MS patients, stroke patients, and healthy control participants. RESULTS: Objective measures of cognitive performance revealed poorer performance for both groups of patients than for controls. A diurnal decline of cognitive performance was only observed for the two groups of patients but not for healthy controls. This decline corresponded to the patients' subjective reports of increasing cognitive fatigue during the day. CONCLUSION: Cognitive fatigue in both MS and stroke patients is not only reflected in subjective ratings but also affects objectively measured performance in cognitive tasks.