Cognitive, behavioral, and brain functional connectivity correlates of fatigue in amyotrophic lateral sclerosis.

INTRODUCTION: Fatigue is defined as a symptom of exhaustion unexplained by drug effects or psychiatric disorders and comprises two main components (i.e., central or "mental" and peripheral or "physical" components), both influencing global disability in amyotrophic lateral sclerosis (ALS). We aim at investigating the clinical correlations between "physical" and "mental" components of fatigue, measured by the Multidimensional Fatigue Inventory scale, and motor and cognitive/behavioral disability in a large sample of patients with ALS. We also investigated the correlations between these measures of fatigue and resting-state functional connectivity of brain functional magnetic resonance imaging (RS-fMRI) large-scale networks in a subset of patients. METHODS: One hundred and thirty ALS patients were assessed for motor disability, cognitive and behavioral dysfunctions, fatigue, anxiety, apathy, and daytime sleepiness. Moreover, the collected clinical parameters were correlated with RS-fMRI functional connectivity changes in the large-scale brain networks of 30 ALS patients who underwent MRI. RESULTS: Multivariate correlation analysis revealed that "physical" fatigue was related to anxiety and respiratory dysfunction, while "mental" fatigue was related to memory impairment and apathy. Moreover, the mental fatigue score was directly related to functional connectivity in the right and left insula (within the salience network), and inversely related to functional connectivity in the left middle temporal gyrus (within the default mode network). CONCLUSIONS: Although the "physical" component of fatigue may be influenced by the disease itself, in ALS the "mental" component of fatigue correlates with cognitive and behavioral impairment, as well as with alterations of functional connectivity in extra-motor networks.

The neural correlates of mental fatigue and reward processing: A task-based fMRI study.

Increasing time spent on the task (i.e., the time-on-task (ToT) effect) often results in mental fatigue. Typical effects of ToT are decreasing levels of task-related motivation and the deterioration of cognitive performance. However, a massive body of research indicates that the detrimental effects can be reversed by extrinsic motivators, for example, providing rewards to fatigued participants. Although several attempts have been made to identify brain areas involved in mental fatigue and related reward processing, the neural correlates are still less understood. In this study, we used the psychomotor vigilance task to induce mental fatigue and blood oxygen-level-dependent functional magnetic resonance imaging to investigate the neural correlates of the ToT effect and the reward effect (i.e., providing extra monetary reward after fatigue induction) in a healthy young sample. Our results were interpreted in a recently proposed neurocognitive framework. The activation of the right middle frontal gyrus, right insula and right anterior cingulate gyrus decreased as fatigue emerged and the cognitive performance dropped. However, after providing an extra reward, the cognitive performance, as well as activation of these areas, increased. Moreover, the activation levels of all of the mentioned areas were negatively associated with reaction times. Our results confirm that the middle frontal gyrus, insula and anterior cingulate cortex play crucial roles in cost-benefit evaluations, a potential background mechanism underlying fatigue, as suggested by the neurocognitive framework.

Mental fatigue correlates with depression of task-related network and augmented DMN activity but spares the reward circuit.

Long-lasting and demanding cognitive activity typically leads to mental fatigue (MF). Indirect evidence suggests that MF may be caused by altered motivational processes. Here, we hypothesized that if MF consists in an alteration of motivational states, brain functional changes induced by MF could specifically affect the brain motivation circuit. In order to test this hypothesis, we devised a functional neuroimaging protocol to detect altered brain activity in reward-related brain regions in relation to cognitively induced mental fatigue. Twenty-five healthy participants underwent a FATIGUE and a CONTROL session on different days. In the FATIGUE session, MF was induced by performing a demanding cognitive task (adapted Stroop task) during 90 min, whereas in the CONTROL session, participants were asked to read magazines for the same period of time. We measured the neural consequences of the MF induction during a working memory task (Missing Number task) while modulating extrinsic motivation with block-wise variations in monetary reward. We also tracked participants' momentary fatigue, anxiety state and intrinsic motivation prior to and following the MF inducement and measurement. Accuracy on the Missing Number Task was lower in the FATIGUE than in the CONTROL condition. Furthermore, subjective MF, but not its behavioral manifestations, was associated with hypoactivity of the task-evoked neural responses. Importantly, activity in regions modulated by reward showed no differences between FATIGUE and CONTROL sessions. In parallel, subjective MF correlated with increased on-task activity and resting-state functional connectivity in the default mode network. These results indicate that subjective mental fatigue is not associated with altered activity in the brain motivation circuit but rather with hypoactivity in task-specific brain regions as well as relative increases of activity and connectivity in the default mode network during and after the task.

Neurological Outcome, Mental Fatigue, and Occurrence of Aneurysms >15 Years After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Long-term data on neurological and radiological outcome after aneurysmal subarachnoid hemorrhage (aSAH) are scarce. The aim of this study was to report neurological and radiological outcome >15 years after aSAH. METHODS: Patients with aSAH who were randomly assigned to endovascular treatment (EVT) or microsurgical treatment (MST) during 1997-2001 were included. Main end points were neurological outcome assessed by modified Rankin Scale, fatigue assessed by mental fatigue scale, and radiological outcome assessed by magnetic resonance angiography. Results for mental fatigue scale were compared with a control group. RESULTS: After 15-21 years, 46 (62.2%) of the 74 survivors replied to a questionnaire. Of these patients, 18 received MST, and 28 received EVT. Modified Rankin Scale score of 0-2 was found in 100% of patients in the EVT group and 88.8% of patients in the MST group. Moderate or severe mental fatigue was found in 7/28 patients (25%) in the EVT group and 7/18 patients (38.8%) in the MST group (P < 0.05), whereas moderate or severe mental fatigue was observed in 3/34 patients (8.9%) in the control group. Magnetic resonance angiography was performed in 29 patients. In the EVT group, new neck remnants were found in 2/16 patients (12.5%), and de novo aneurysm was found in 2/16 patients (12.5%). In the MST group, de novo aneurysm was found in 1/13 patients (7.7%). CONCLUSIONS: Neurological outcome at long-term follow-up after aSAH was good; however, mental fatigue was overrepresented in patients compared with healthy control subjects regardless of treatment modality. Residual or de novo aneurysm was found in 17% of patients warranting radiological long-term follow-up.

Thalamic shape abnormalities in patients with multiple sclerosis-related fatigue.

Thalamus plays an important role in the pathogenesis of multiple sclerosis-related fatigue (MSrF). However, the thalamus is a heterogeneous structure and the specific thalamic subregions that are involved in this condition are unclear. Here, we used thalamic shape analysis for the detailed localization of thalamic abnormalities in MSrF. Using the Modified Fatigue Impact Scale, we measured fatigue in 42 patients with relapsing-remitting multiple sclerosis (MS). The thalamic shape was extracted from T1w images using an automated pipeline. We investigated the association of thalamic surface deviations with the severity of global fatigue and its cognitive, physical and psychosocial subdomains. Cognitive fatigue was correlated with an inward deformity of the left anteromedial thalamic surface, but no other localized shape deviation was observed in correlation with global, physical or psychosocial fatigue. Our findings indicate that the left anteromedial thalamic subregions are implicated in cognitive fatigue, possibly through their role in reward processing and cognitive and executive functions.

Mental fatigue in stress-related exhaustion disorder: Structural brain correlates, clinical characteristics and relations with cognitive functioning.

Emerging evidence suggests that mental fatigue is a central component of the cognitive and clinical characteristics of stress-related exhaustion disorder (ED). Yet, the underlying mechanisms of mental fatigue in this patient group are poorly understood. The aim of this study was to investigate cortical and subcortical structural neural correlates of mental fatigue in patients with ED, and to explore the association between mental fatigue and cognitive functioning. Fifty-five patients with clinical ED diagnosis underwent magnetic resonance imaging. Mental fatigue was assessed using the Concentration subscale from the Checklist Individual Strength. Patients with high levels of mental fatigue (n = 30) had smaller caudate and putamen volumes compared to patients with low-moderate levels of mental fatigue (n = 25). No statistically significant differences in cortical thickness were observed between the groups. Mediation analysis showed that mental fatigue mediated the relationship between caudate volume and working memory; specifically, smaller caudate volume was associated with higher level of mental fatigue and mental fatigue was positively associated with working memory performance. Our findings demonstrate that the structural integrity of the striatum is of relevance for the subjective perception of mental fatigue in ED, while also highlighting the complex relationship between mental fatigue, cognitive performance and its neural underpinnings.

The influence of mental fatigue on the face and word encoding activations.

OBJECTIVES: Memory is an important brain function, and is impaired with brain lesions. Resection of the lesion is one solution for that, but presurgical planning (PSP) is needed to guide the surgery for maximum removal of the lesion, as well as maximum preservation of the function. Functional Magnetic Resonance Imaging (fMRI) is one of the best approaches for such a purpose, but performing an fMRI study needs careful consideration of the factors which influence its results. Studies have shown that mental fatigue does have the potential to alter brain functions, and therefore this study aims to identify if mental fatigue should also be considered as a confounding factor when performing an fMRI study, particularly for clinical purposes. PATIENTS AND METHODS: Using 57 healthy young volunteers, face and word encoding tasks were performed, with half of the participants performing the memory tasks after a set of language tasks and half of them before that. RESULTS: The results showed that mental fatigue led to increased activity in the bilateral thalamus and caudate in the face encoding task, and in the right thalamus, posterior cingulate and medial temporal lobe in word encoding. In addition, activation was declined with mental fatigue in the left lingual, precuneus, and posterior cingulate gyri in face encoding. CONCLUSION: This study has shown the importance of the number and sequence of cognitive/mental tasks when performing an fMRI study, which could help to obtain more reliable fMRI maps in clinical applications. This finding is also important for performing research/cognitive studies using fMRI.

Structural brain changes in hyperthyroid Graves' disease: protocol for an ongoing longitudinal, case-controlled study in Göteborg, Sweden-the CogThy project.

INTRODUCTION: Cognitive impairment and reduced well-being are common manifestations of Graves' disease (GD). These symptoms are not only prevalent during the active phase of the disease but also often prevail for a long time after hyperthyroidism is considered cured. The pathogenic mechanisms involved in these brain-derived symptoms are currently unknown. The overall aim of the CogThy study is to identify the mechanism behind cognitive impairment to be able to recognise GD patients at risk. METHODS AND ANALYSIS: The study is a longitudinal, single-centre, case-controlled study conducted in Göteborg, Sweden on premenopausal women with newly diagnosed GD. The subjects are examined: at referral, at inclusion and then every 3.25 months until 15 months. Examinations include: laboratory measurements; eye evaluation; neuropsychiatric and neuropsychological testing; structural MRI of the whole brain, orbits and medial temporal lobe structures; functional near-infrared spectroscopy of the cerebral prefrontal cortex and self-assessed quality of life questionnaires. The primary outcome measure is the change in medial temporal lobe structure volume. Secondary outcome measures include neuropsychological, neuropsychiatric, hormonal and autoantibody variables. The study opened for inclusion in September 2012 and close for inclusion in October 2019. It will provide novel information on the effect of GD on medial temporal lobe structures and cerebral cortex functionality as well as whether these changes are associated with cognitive and affective impairment, hormonal levels and/or autoantibody levels. It should lead to a broader understanding of the underlying pathogenesis and future treatment perspectives. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Regional Ethical Review Board in Göteborg, Sweden. The results will be actively disseminated through peer-reviewed journals, national and international conference presentations and among patient organisations after an appropriate embargo time. TRIAL REGISTRATION NUMBER: 44321 at the public project database for research and development in Västra Götaland County, Sweden (https://www.researchweb.org/is/vgr/project/44321).

Spectral and Temporal Feature Learning With Two-Stream Neural Networks for Mental Workload Assessment.

People's mental workload profoundly affects their work efficiency and health. Mental workload assessment can be used to effectively avoid serious accidents caused by excessive mental workload. Both electroencephalogram (EEG) spectral features and its temporal features have proven to be useful in addressing this problem. The fusion of the two types of features can provide rich distinguishing information for improving mental workload assessment. Benefiting from the progress of deep learning, this study proposes the two-stream neural networks (TSNN) for fusing the two types of EEG features. Compared with hand-crafted features, the TSNN can learn and fuse EEG features from the spectral and temporal dimensions automatically without prior knowledge. The TSNN includes a spectral stream and a temporal stream. Each stream consists of a convolutional neural network (CNN) and a temporal convolutional network (TCN) to learn spectral or temporal features from EEG topographic maps. To fuse the learned spectral and temporal information, we concatenate the output of the two streams prior to the fully connected layer. EEG data were collected from 17 subjects who performed n-back tasks with easy, medium, and hard difficulty levels, leading to a three-class mental workload classification. The results show that the TSNN achieves an average accuracy of 91.9%, which is a significant improvement over baseline classifiers based on hand-crafted features. The TSNN also outperforms state-of-the-art deep learning methods developed for EEG classification. The results indicate that the proposed structure is promising for fusing spectral and temporal features for mental workload assessment. In addition, it provides a high-precision approach for potential applications during cognitive activities.

Effective connectivity of mental fatigue: Dynamic causal modeling of EEG data.

BACKGROUND: Recognition of sources in the brain and their interaction with mental fatigue states are interesting subjects for researchers. OBJECTIVE: The aim of this study was to investigate the mental fatigue effects on brain areas by dynamic casual modeling (DCM) parameters that are extracted from event-related potential (ERP) signals which were then estimated based on mental fatigue data with visual stimulation. METHODS: ERP were recorded based on a Continuous Performance Task in four consecutive trials. Active regions and brain sources were extracted by a Multiple Sparse Priors algorithm. RESULTS: Four models are proposed for DCM. The parameters and the structure of the best model were obtained by SPM software for ERP in each of the four trials. CONCLUSION: The results illustrate that an increase of mental fatigue through trials leads to increased likelihood of choosing forward models.

Feeling the force: Changes in a left-lateralized network of brain areas under simulated workday conditions are reflected in subjective mental effort investment.

Investing mental effort is costly, and the investment has to be matched by a reward to make a person engage in task performance. However, the neural structures underlying the continued management of mental effort are not known. Previous work has identified left-lateralized structures, most prominently the left anterior Insular Cortex (aIC) as regions implied in post-hoc evaluation and also anticipation of mental effort investment. We present a study aimed at identifying neural structures that are sensitive to changes in both task load and fatigue-induced state load. Sixteen healthy participants performed an n-back task before and after a fatigue-inducing day in a helicopter simulator or a free day. Subjective mental effort ratings showed an interaction of the effects of both task and state load changes, with a reduced effect of task load during the fatigued state. Testing for the same interaction effect in a whole-brain functional MRI data, we found a left-lateralized group of clusters in aIC, the anterior cingulate cortex, the dorsal striatum and frontal eye field and M1. We discuss the possible role of these areas and also the relevance of our findings in the light of the proposed opportunity cost model of mental effort.

Fronto-Parietal Subnetworks Flexibility Compensates For Cognitive Decline Due To Mental Fatigue.

Fronto-parietal subnetworks were revealed to compensate for cognitive decline due to mental fatigue by community structure analysis. Here, we investigate changes in topology of subnetworks of resting-state fMRI networks due to mental fatigue induced by prolonged performance of a cognitively demanding task, and their associations with cognitive decline. As it is well established that brain networks have modular organization, community structure analyses can provide valuable information about mesoscale network organization and serve as a bridge between standard fMRI approaches and brain connectomics that quantify the topology of whole brain networks. We developed inter- and intramodule network metrics to quantify topological characteristics of subnetworks, based on our hypothesis that mental fatigue would impact on functional relationships of subnetworks. Functional networks were constructed with wavelet correlation and a data-driven thresholding scheme based on orthogonal minimum spanning trees, which allowed detection of communities with weak connections. A change from pre- to posttask runs was found for the intermodule density between the frontal and the temporal subnetworks. Seven inter- or intramodule network metrics, mostly at the frontal or the parietal subnetworks, showed significant predictive power of individual cognitive decline, while the network metrics for the whole network were less effective in the predictions. Our results suggest that the control-type fronto-parietal networks have a flexible topological architecture to compensate for declining cognitive ability due to mental fatigue. This community structure analysis provides valuable insight into connectivity dynamics under different cognitive states including mental fatigue.

On the role of the amygdala for experiencing fatigue in patients with multiple sclerosis.

BACKGROUND: Recently, we proposed a model explaining the origin of fatigue in multiple sclerosis (MS) patients. This model assumes that the feeling of fatigue results from inflammation-induced information processing within interoceptive brain areas. OBJECTIVES: To investigate the association between self-reported cognitive fatigue and structural integrity of interoceptive brain areas in MS patients. METHODS: 95 MS patients and 28 healthy controls participated in this study. All participants underwent diffusion tensor MRI and fractional anisotropy data were calculated for the amygdala, the stria terminalis and the corpus callosum, a non-interoceptive brain area. Based on the cognitive fatigue score of the Fatigue Scale for Motor and Cognition, patients were divided into moderately cognitively fatigued (cognitive fatigue score ≥ 28) and cognitively non-fatigued (cognitive fatigue score < 28) MS patients. Healthy controls were recruited as a third group. Repeated measures analyses of covariance, controlling for age, depression and brain atrophy, were performed to investigate whether the factor Group had a significant effect on the fractional anisotropy data. RESULTS: A significant effect of Group was observed for the amygdala (F = 3.389, p = 0.037). MS patients without cognitive fatigue presented lower values of the amygdala than MS patients with cognitive fatigue and healthy controls. For the stria terminalis and the corpus callosum, no main effect of Group was observed. CONCLUSION: The structural integrity of the amygdala in non-fatigued MS patients appears to be reduced. According to our model this might indicate that the absence of fatigue in non-fatigued MS patients might result from disturbed inflammation-induced information processing in the amygdala.

The Reorganization of Human Brain Networks Modulated by Driving Mental Fatigue.

The organization of the brain functional network is associated with mental fatigue, but little is known about the brain network topology that is modulated by the mental fatigue. In this study, we used the graph theory approach to investigate reconfiguration changes in functional networks of different electroen-cephalography (EEG) bands from 16 subjects performing a simulated driving task. Behavior and brain functional networks were compared between the normal and driving mental fatigue states. The scores of subjective self-reports indicated that 90 min of simulated driving-induced mental fatigue. We observed that coherence was significantly increased in the frontal, central, and temporal brain regions. Furthermore, in the brain network topology metric, significant increases were observed in the clustering coefficient (Cp) for beta, alpha, and delta bands and the character path length (Lp) for all EEG bands. The normalized measures γ showed significant increases in beta, alpha, and delta bands, and λ showed similar patterns in beta and theta bands. These results indicate that functional network topology can shift the network topology structure toward a more economic but less efficient configuration, which suggests low wiring costs in functional networks and disruption of the effective interactions between and across cortical regions during mental fatigue states. Graph theory analysis might be a useful tool for further understanding the neural mechanisms of driving mental fatigue.

A Passive EEG-BCI for Single-Trial Detection of Changes in Mental State.

Traditional brain-computer interfaces often exhibit unstable performance over time. It has recently been proposed that passive brain-computer interfaces may provide a way to complement and stabilize these traditional systems. In this study, we investigated the feasibility of a passive brain-computer interface that uses electroencephalography to monitor changes in mental state on a single-trial basis. We recorded cortical activity from 15 locations while 11 able-bodied adults completed a series of challenging mental tasks. Using a feature clustering algorithm to account for redundancy in EEG signal features, we classified self-reported changes in fatigue, frustration, and attention levels with 74.8 ± 9.1%, 71.6 ± 5.6%, and 84.8 ± 7.4% accuracy, respectively. Based on the most frequently-selected features across all participants, we note the importance of the frontal and central electrodes for fatigue detection, posterior alpha band and frontal beta band activity for frustration detection, and posterior alpha band activity for attention detection. Future work will focus on integrating these results with an active brain-computer interface.

Cognitive fatigue is associated with reduced anterior internal capsule integrity in veterans with history of mild to moderate traumatic brain injury.

No known studies have directly examined white matter microstructural correlates of cognitive fatigue post-TBI in a Veteran sample. We therefore investigated the relationship between cognitive fatigue and white matter integrity in Veterans with history of mild to moderate TBI (mmTBI). 59 Veterans (TBI = 34, Veteran Controls [VCs] = 25]) with and without history of mmTBI underwent structural 3T DTI scans and completed questionnaires related to cognitive fatigue and psychiatric symptoms. Tractography was employed on six regions of interest, including the anterior and posterior limbs of the internal capsule; genu; body and splenium of the corpus callosum; and cingulum bundle. Group analyses revealed that those with history of mmTBI displayed significantly greater levels of cognitive fatigue relative to those with no history of head injury (p = .02). Within the mmTBI group, independent of psychiatric symptoms, decreased white matter microstructural integrity of the left anterior internal capsule was associated with greater levels of cognitive fatigue (p = .01). Results show that the subjective experience of cognitive fatigue following neurotrauma may be linked to the disruption of striato-thalamo-cortical tracts that are important in mediating arousal and higher-order cognitive processes. These findings build upon those from existing functional neuroimaging studies in those with history of TBI, providing further evidence for the neural basis of cognitive fatigue in head injured adults.

Montmorency Tart cherries (Prunus cerasus L.) modulate vascular function acutely, in the absence of improvement in cognitive performance.

Cerebral blood volume and metabolism of oxygen decline as part of human ageing, and this has been previously shown to be related to cognitive decline. There is some evidence to suggest that polyphenol-rich foods can play an important role in delaying the onset or halting the progression of age-related health disorders such as CVD and Alzheimer's disease and to improve cognitive function. In the present study, an acute, placebo-controlled, double-blinded, cross-over, randomised Latin-square design study with a washout period of at least 14 d was conducted on twenty-seven, middle-aged (defined as 45-60 years) volunteers. Participants received either a 60 ml dose of Montmorency tart cherry concentrate (MC), which contained 68·0 (sd 0·26) mg cyanidin-3-glucoside/l, 160·75 (sd 0·55) mean gallic acid equivalent/l and 0·59 (sd 0·02) mean Trolox equivalent/l, respectively, or a placebo. Cerebrovascular responses, cognitive performance and blood pressure were assessed at baseline and 1, 2, 3 and 5 h following consumption. There were significant differences in concentrations of total Hb and oxygenated Hb during the task period 1 h after MC consumption (P≤0·05). Furthermore, MC consumption significantly lowered systolic blood pressure (P≤0·05) over a period of 3 h, with peak reductions of 6±2 mmHg at 1 h after MC consumption relative to the placebo. Cognitive function and mood were not affected. These results show that a single dose of MC concentrate can modulate certain variables of vascular function; however, this does not translate to improvements in cognition or mood.

A study of cognitive fatigue in Multiple Sclerosis with novel clinical and electrophysiological parameters utilizing the event related potential P300.

BACKGROUND: Although cognitive fatigue plays a significant part in Multiple Sclerosis (MS) related impairment, knowledge regarding it is largely lacking. Until now, not many tools are available to a clinician to detect cognitive fatigue. The subjective tools of fatigue have never been reliable.tabl OBJECTIVES: To assess the prevalence and clinical/ demographic profile of cognitive fatigue in MS using novel clinical and electrophysiological measures and to find their accuracy. We also aimed to test the three leading hypotheses - the temporal fatigue, cognitive load and cognitive domain hypotheses of cognitive fatigue in MS. METHODS: 50 consecutive MS patients attending the Neurology OPD in Madras Medical College, Chennai from May 2015 to February 2016 satisfying the 2010 revised McDonald criteria for MS with an equal number of matched controls were recruited. Modified versions (a shorter version, and longer and more demanding versions) of the Stroop test, symbol digit modalities test, and serial addition tests were used in addition to modified tests of P300 latency and amplitude each specifically tailored to reveal cognitive fatigue. RESULTS: Out of the seven measures of cognitive fatigue used, 46% (n=23) of MS patients had impairment in two or more of the scores compared to that of 8% (n=4) in the healthy control group. The Expanded disability status scale (EDSS) scores were significantly higher for MS patients with cognitive fatigue compared to those without. All the clinical and electrophysiological measures used in this study had a relatively high sensitivity and specificity. In addition, all the clinical measures correlated with the electrophysiological measures of cognitive fatigue in this study. Our data also supported all three hypotheses implying that cognitive fatigue in MS may be a multifaceted entity. CONCLUSION: Cognitive fatigue is widely prevalent in MS and can be detected with specific tools. The tools developed and described in this study may be used as an effective means of detecting cognitive fatigue in MS patients and thus allowing patients to realise their limitations. Institution of appropriate remedial measures like advising such patients to break up a more cognitively demanding task into smaller subtasks may help to improve their quality of life.

Hyperconnectivity of the dorsolateral prefrontal cortex following mental effort in multiple sclerosis patients with cognitive fatigue.

OBJECTIVE: To investigate the dynamic temporal changes of brain resting-state functional connectivity (RS-FC) following mental effort in multiple sclerosis (MS) patients with cognitive fatigue (CF). METHODS: Twenty-two MS patients, 11 with (F) and 11 without CF, and 12 healthy controls were included. Separate RS-FC scans were acquired on a 3T MR scanner immediately before (t0), immediately after (t1) and 30 minutes after (t2) execution of the paced auditory serial addition test (PASAT), a cognitively demanding task. Subjectively perceived CF after PASAT execution was also assessed. RS-FC changes were investigated by using a data-driven approach (the Intrinsic Connectivity Contrast-power), complemented by a priori defined regions of interest analyses. RESULTS: The F-group patients experienced stronger RS-FC at t2 between the left superior frontal gyrus (L-SFG) and occipital, frontal and temporal areas, which increased over time after PASAT execution. In the F-group patients, the L-SFG was hyperconnected at t1 with the left caudate nucleus and hypoconnected at t2 with the left anterior thalamus. These variations were correlated with both subjectively perceived and clinically assessed CF, and-for the left thalamus-with PASAT performance. CONCLUSION: The development of cortico-cortical and cortico-subcortical hyperconnectivity following mental effort is related to CF symptoms in MS patients.

Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome.

OBJECTIVE: The purposes of this study were to compare functional imaging under control and experimental conditions among patients with chronic fatigue syndrome (CFS) and healthy persons and to examine perceived and objective performance on a test of attention and working memory previously found to be difficult for persons with CFS. METHODS: Single-photon emission computerized tomography scans were completed on 15 subjects with CFS and 15 healthy persons twice: at rest and when performing the Paced Auditory Serial Addition Test (PASAT). RESULTS: No group differences were found for performance on the PASAT despite CFS subjects' perceptions of exerting more mental effort to perform the task than healthy subjects. Inspection of the aggregate scans by group and task suggested a pattern of diffuse regional cerebral blood flow among subjects with CFS in comparison with the more focal pattern of regional cerebral blood flow seen among healthy subjects. Between-group region-of-interest analysis revealed that although CFS subjects showed less perfusion in the anterior cingulate region, the change in CFS subjects' activation of the left anterior cingulate region during the PASAT was greater than that observed for healthy subjects. The differences were not attributable to lesser effort by the subjects with CFS, confounding effects of mood perturbation, or to poorer performance on the experimental task. CONCLUSIONS: Further research regarding CFS subjects' diffuse cerebral perfusion and its relationship to inefficient neuropsychological performance is warranted.