The present study investigated the neural correlates of cognitive fatigue in Multiple Sclerosis (MS), looking specifically at the relationship between self-reported fatigue and objective measures of cognitive fatigue. In Experiment 1, functional magnetic resonance imaging (fMRI) was used to examine where in the brain BOLD activity covaried with “state” fatigue, assessed during performance of a task designed to induce cognitive fatigue while in the scanner. In Experiment 2, diffusion tensor imaging (DTI) was used to examine where in the brain white matter damage correlated with increased “trait” fatigue in individuals with MS, assessed by the Fatigue Severity Scale (FSS) completed outside the scanning session. During the cognitively fatiguing task, the MS group had increased brain activity associated with fatigue in the caudate as compared with HCs. DTI findings revealed that reduced fractional anisotropy in the anterior internal capsule was associated with increased self-reported fatigue on the FSS. Results are discussed in terms of identifying a “fatigue-network” in MS.

Emotional processing deficits have recently been identified in individuals with traumatic brain injury (TBI), specifically in the domain of facial affect recognition. However, the neural networks underlying these impairments have yet to be identified. In the current study, 42 individuals with moderate to severe TBI and 23 healthy controls performed a task of facial affect recognition (Facial Emotion Identification Test (FEIT)) in order to assess their ability to identify and discriminate six emotions: happiness, sadness, anger, surprise, shame, and fear. These individuals also underwent structural neuroimaging including diffusion tensor imaging to examine white matter (WM) integrity. Correlational analyses were performed to determine where in the brain WM damage was associated with performance on the facial affect recognition task. Reduced performance on the FEIT was associated with reduced WM integrity (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) in the inferior longitudinal fasciculus and inferior-fronto-occipital fasciculus in individuals with TBI. Poor performance on the task was additionally associated with reduced gray matter (GM) volume in lingual gyrus and parahippocampal gyrus. The results implicate a pattern of WM and GM damage in TBI that may play a role in emotional processing impairments.

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Metabolic changes corresponded well with structural changes in motor and extramotor areas, and sometimes occurred even in the absence of GM volume reduction. Coincident structural and functional GM changes suggest that neurodegeneration may occur as "neuronopathy" in patients with ALS-FTD.

ObjectiveTo investigate whether fatigue induced by an intermittent motor task in patients with cancer-related fatigue (CRF) is more central or peripheral.MethodsTen patients with CRF who were off chemo and radiation therapies and 14 age-matched healthy controls were enrolled. Participants completed a Brief Fatigue Inventory (BFI) and performed a fatigue task consisting of intermittent elbow-flexion contractions at submaximal (40% maximal voluntary contraction) intensity till self-perceived exhaustion. Twitch force was elicited by an electrical stimulation applied to the biceps brachii muscle. The relative degree of peripheral (muscle) vs. central contribution to fatigue induced by the intermittent motor task (IMT) was assessed using twitch force ratio (TFratio) defined as post IMT twitch force to pre IMT twitch force. The total number of trials (intermittent contractions) and total duration of all trials performed by each subject were also quantified.ResultsBFI scores were higher (p<0.001) in CRF than controls, indicating greater feeling of fatigue in CRF patients than controls. A significantly smaller number of trials and shorter total duration of the trials (p<0.05) were observed in CRF than control participants. The TFratio (0.81±0.05) in CRF was higher (p<0.05) compared with that of controls (0.62±0.05), suggesting CRF patients experienced a significantly lower degree of muscle (peripheral) fatigue at the time of perceived exhaustion.ConclusionConsistent with prior findings for fatigue under submaximal sustained contraction, our results indicate that motor fatigue in CRF is more of central than peripheral origin during IMT. Significant central fatigue in CRF patients limits their ability to prolong motor performance.

BackgroundBecause our previous study showed disparate voxel based morphometry (VBM) results between SPM and FSL softwares in the brain of amyotrophic lateral sclerosis patients with frontotemporal dementia (ALS-FTD), we investigated which VBM results may more represent atrophy by comparing with Freesurfer’s cortical volume and thickness measures.MethodsMRI at 1.5 T was obtained during routine clinical imaging of ALS-FTD patients (n = 18) and in unaffected neurologic controls (n = 15). Gray matter (GM) VBM analysis was carried out using FSL and SPM. Cortical thickness and volume analysis was performed using Freesurfer.ResultsGM volume was significantly (p < 0.05) reduced in both motor and extra motor regions in ALS- FTD when compared to unaffected neurologic controls in FSL and Freesurfer but not in SPM. Dice similarity index for cortical GM volume changes between FSL and Freesurfer was 0.30 for motor and 0.31 for non-motor regions as opposed to 0 (motor) and 0.02 (non-motor) between SPM and Freesurfer.ConclusionGM volume changes using FSL showed similar pattern with Freesurfer cortical volume and thickness changes in contrast to SPM results. Our results suggest that, at least for our dataset, VBM results obtained using FSL software should be considered as more representative of GM atrophy.

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder. Current diagnosis time is about 12-months due to lack of objective methods. Previous brain white matter voxel based morphometry (VBM) studies in ALS reported inconsistent results. Fractal dimension (FD) has successfully been used to quantify brain WM shape complexity in various neurological disorders and aging, but not yet studied in ALS. Therefore, we investigated WM morphometric changes using FD analyses in ALS patients with different clinical phenotypes. We hypothesized that FD would better capture clinical features of the WM morphometry in different ALS phenotypes than VBM analysis. High resolution MRI T1-weighted images were acquired in controls (n = 11), and ALS patients (n = 89). ALS patients were assigned into four subgroups based on their clinical phenotypes.VBM analysis was carried out using SPM8. FD values were estimated for brain WM skeleton, surface and general structure in both controls and ALS patients using our previously published algorithm. No significant VBM WM changes were observed between controls and ALS patients and among the ALS subgroups. In contrast, significant (p<0.05) FD reductions in skeleton and general structure were observed between ALS with dementia and other ALS subgroups. No significant differences in any of the FD measures were observed between control and ALS patients. FD correlated significantly with revised ALS functional rating scale (ALSFRS-R) score a clinical measure of function. Results suggest that brain WM shape complexity is more sensitive to ALS disease process when compared to volumetric VBM analysis and FD changes are dependent on the ALS phenotype. Correlation between FD and clinical measures suggests that FD could potentially serve as a biomarker of ALS pathophysiology, especially after confirmation by longitudinal studies.

The differences in GM volume atrophy measures found by FSL and SPM analytic methods indicate that variable results in previous VBM studies may arise from differences in their image processing algorithms and statistical models.