Pavel Hok

Objective: To evaluate central and peripheral correlates of motor control using functional magnetic resonance imaging (fMRI) and surface electromyography (EMG), with a focus on the added value of EMG-informed analysis during movement of the lower limb in healthy controls. Methods: Twenty participants performed dorsi-/plantarflexion of the ankle (Ankle) and gait imagery (GI) in a block design during fMRI. Accelerometry (Acc) and surface EMG from tibialis anterior (TA) activity were recorded and included as regressors in five analysis models, either with or without temporal derivative (TD) to account for time shift in the task regressor. Voxel-wise analyses complemented by post-hoc region-of-interest (ROI) analyses were performed to compare the amount of variability explained by the models. Results: Inclusion of either Acc or EMG on top of the task regressor explained robustly fMRI signal variability in the primary sensorimotor cortices. On top of Acc, EMG additionally explained activation variability mainly in the contralateral thalamus and the secondary somatosensory cortex (S2). This effect was, however, mainly driven by spontaneous signal fluctuations at rest and during imagery. Comparisons between models with and without TD revealed consistent differences in the cerebellum and thalamus across tested models, suggesting that subcortical structures may involve transient signal changes when switching between movement and rest. Conclusion: Including EMG in fMRI analysis enhances specificity in detecting motor-related brain activity and enables differentiation of spontaneous or unpredicted motor behavior. TD improved signal detection in the primary sensorimotor cortices, but may have a detrimental effect on signal detection in other, mostly subcortical regions, likely reflecting their different temporal signal dynamics.

Creativity is one of the unique cognitive constructs in human beings and its neurobiological correlates are one of the current hot topics in neuroscience. The “Different Hearing” program (DHP) is an educational activity aimed at stimulating musical creativity by means of group composing in the classroom, alternative to the mainstream model of music education in Czechia. In our previous study, the data from task-related functional MRI with passive listening was analyzed. The results suggested that DHP training modified the response to diverse sound samples, differentially changing the engagement of functional networks known to be related to creative thinking, namely, increasing default mode network activation and decreasing activation of executive and salience networks. In the present study, we hypothesized that the DHP short-term (2 days) intense workshop would also induce changes in the resting-state networks that were significantly modified during task. To investigate it, seed-based, ROI-to-ROI resting-state functional connectivity and degree centrality analysis were performed on the acquired resting-state fMRI data. The results showed no significant group-by-time interaction.

Purpose To evaluate diffusion weighted imaging (DWI) with advanced diffusion models, optical coherence tomography (OCT), and automatic retinal oximetry as potential biomarkers for visual deficits after optic neuritis (ON). Methods Twenty-five patients with acute unilateral ON underwent brain DWI, OCT, and oximetry at the treatment initiation, and 3 and 6 months later. Additionally, 56 healthy volunteers with normal vision were examined once. Clinical outcomes were best-corrected visual acuity (BCVA) and contrast sensitivity. Predictors included retinal nerve fiber layer (RNFL) thickness, arteriolar and venular oxygen saturation (AS, VS), and arterio-venous difference (AVD) in the affected eye as well as DWI parameters from both optic radiations. Results Multivariate analysis of variance (MANOVA) for baseline DWI indicated higher secondary partial volume fraction (f2) in patients, while both groups exhibited significant left-right differences for all DWI parameters. Longitudinal analysis in 17 patients with follow-up data revealed a multivariate effect of time when adjusted for affected side and time since onset, however, no DWI parameters changed significantly on a univariate level. Stratified unadjusted model indicated lower overall fractional anisotropy (FA) in patients with incomplete recovery. On uncorrected level, baseline FA and oximetry (VS) were correlated with follow-up BCVA at month 6, while axonal diffusivity (AD) predicted follow-up VS and AVD. In turn, baseline VS and AVD predicted follow-up RNFL thickness. Conclusions DWI and retinal oximetry are promising early predictors of visual function outcome after ON. Translational Relevance DWI and retinal oximetry are potentially suitable for patient stratification in studies investigating novel therapeutic interventions.

Background and purpose: Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting‐state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph‐theory‐based degree rank order disruption index (k_D) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross‐sectional fMRI analysis.Methods: Differentiation between PwMS and healthy controls (HCs) using k_D and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion‐weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability.Results: Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower k_D in PwMS than in HCs (median −0.30/−0.06, interquartile range 0.55/0.54; p = 0.009, Mann–Whitney U test), yielding acceptable yet non‐superior differentiation (area under curve 0.64). k_D and degree in medial prefrontal cortex (MPFC) correlated with CI (k_D/MPFC Spearman's ρ = 0.32/−0.45, p = 0.019/0.001, n = 55). k_D also explained fatigue (ρ = −0.34, p = 0.010, n = 56) but neither gait nor disability.Conclusions: k_D is a potential biomarker of CI and fatigue warranting further validation.

A bstract: Background and Objectives: The aim of this secondary data analysis was to determine whether multiple sclerosis (MS) is associated with changes in global degree rank order disruption index ( k _D ), a graph theory-based functional connectivity measure representing shift in overall distribution of nodal degree centrality. Additionally, we tested the relationship between k _D and MS symptoms (cognitive and motor impairment, fatigue, and global disability). Methods: Global k _D was computed in a pre-existing cross-sectional fMRI dataset and compared between patients with MS (PwMS) and healthy controls (HCs). Group differentiation was tested against other known biomarkers in MS (regional degree centrality, structural MRI with volumetry, diffusion-weighted imaging, lesion mapping) using receiver operating characteristic and logistic regression analysis. Associations between k _D and cognitive processing speed (Symbol Digit Modalities Test), fatigue (Fatigue Scale for Motor and Cognitive Functions), gait (Timed Up and Go Test), and disability (Expanded Disability Status Scale [EDSS]) were evaluated using Spearman correlation coefficient and ordinal regression adjusted for structural imaging, age, sex, and disease duration. Results: Analysis included 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years). Global k _D was lower in PwMS (median −0.30, inter-quartile range [IQR] 0.55) than in HCs (median −0.06, IQR 0.54; p = 0.009, Mann-Whitney U test). k _D yielded acceptable differentiation between groups (area under curve 0.64), but did not improve such differentiation on top of structural imaging. Both k _D and regional degree in medial prefrontal cortex (MPFC) were correlated with cognitive decline ( k _D : Spearman’s ρ = 0.32, p = 0.019; MPFC: ρ = −0.45, p = 0.001, n = 55), while k _D was also correlated with fatigue ( ρ = −0.34, p = 0.010, n = 56), but not with EDSS ( ρ = −0.06, p = 0.674, n = 56) or gait ( ρ = −0.18, p = 0.211, n = 52). k _D significantly explained cognitive impairment ( χ ² = 4.49, p = 0.034) and fatigue ( χ ² = 7.18, p = 0.007). Discussion: Our data provide evidence that k _D is a potential biomarker of cognitive decline and fatigue. Further cross-validations are required to assess its generalizability.

BACKGROUND: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function. METHODS: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity). RESULTS: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices ( r [21]=0.49; P= 0.025) and superior longitudinal fascicle ( r [21]=0.51; P=0 .018) with Fugl-Meyer upper extremity. CONCLUSIONS: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.