Individual differences in white matter microstructure reflect variation in functional connectivity during action choice.

The relation between brain structure and function is of fundamental importance in neuroscience. Comparisons between behavioral and brain imaging measures suggest that variation in brain structure correlates with the presence of specific skills[1-3]. Behavioral measures, however, reflect the integrated function of multiple brain regions. Rather than behavior, a physiological index of function could be a more sensitive and informative measure with which to compare structural measures. Here, we test for a relationship between a physiological measure of functional connectivity between two brain areas during a simple decision making task and a measure of structural connectivity. Paired-pulse transcranial magnetic stimulation indexed functional connectivity between two regions important for action choices: premotor and motor cortex. Fractional anisotropy (FA), a marker of microstructural integrity, indexed structural connectivity. Individual differences in functional connectivity during action selection show highly specific correlations with FA in localised regions of white matter interconnecting regions including the premotor and motor cortex. Probabilistic tractography[4, 5], a technique for identifying fibre pathways from diffusion-weighted imaging (DWI), reconstructed the anatomical networks linking the component brain regions involved in making decisions. These findings demonstrate a relationship between individual differences in functional and structural connectivity within human brain networks central to action choice

Fiber Orientation Estimation Guided by a Deep Network

Diffusion magnetic resonance imaging (dMRI) is currently the only tool for noninvasively imaging the brain's white matter tracts. The fiber orientation (FO) is a key feature computed from dMRI for fiber tract reconstruction. Because the number of FOs in a voxel is usually small, dictionary-based sparse reconstruction has been used to estimate FOs with a relatively small number of diffusion gradients. However, accurate FO estimation in regions with complex FO configurations in the presence of noise can still be challenging. In this work we explore the use of a deep network for FO estimation in a dictionary-based framework and propose an algorithm named Fiber Orientation Reconstruction guided by a Deep Network (FORDN). FORDN consists of two steps. First, we use a smaller dictionary encoding coarse basis FOs to represent the diffusion signals. To estimate the mixture fractions of the dictionary atoms (and thus coarse FOs), a deep network is designed specifically for solving the sparse reconstruction problem. Here, the smaller dictionary is used to reduce the computational cost of training. Second, the coarse FOs inform the final FO estimation, where a larger dictionary encoding dense basis FOs is used and a weighted l1-norm regularized least squares problem is solved to encourage FOs that are consistent with the network output. FORDN was evaluated and compared with state-of-the-art algorithms that estimate FOs using sparse reconstruction on simulated and real dMRI data, and the results demonstrate the benefit of using a deep network for FO estimation.Comment: A shorter version is accepted by MICCAI 201

Learning-based Ensemble Average Propagator Estimation

By capturing the anisotropic water diffusion in tissue, diffusion magnetic resonance imaging (dMRI) provides a unique tool for noninvasively probing the tissue microstructure and orientation in the human brain. The diffusion profile can be described by the ensemble average propagator (EAP), which is inferred from observed diffusion signals. However, accurate EAP estimation using the number of diffusion gradients that is clinically practical can be challenging. In this work, we propose a deep learning algorithm for EAP estimation, which is named learning-based ensemble average propagator estimation (LEAPE). The EAP is commonly represented by a basis and its associated coefficients, and here we choose the SHORE basis and design a deep network to estimate the coefficients. The network comprises two cascaded components. The first component is a multiple layer perceptron (MLP) that simultaneously predicts the unknown coefficients. However, typical training loss functions, such as mean squared errors, may not properly represent the geometry of the possibly non-Euclidean space of the coefficients, which in particular causes problems for the extraction of directional information from the EAP. Therefore, to regularize the training, in the second component we compute an auxiliary output of approximated fiber orientation (FO) errors with the aid of a second MLP that is trained separately. We performed experiments using dMRI data that resemble clinically achievable $q$-space sampling, and observed promising results compared with the conventional EAP estimation method.Comment: Accepted by MICCAI 201

A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain

Higher levels of physical fitness or activity (PFA) have been shown to have beneficial effects on cognitive function and grey matter volumes in older adults. However, the relationship between PFA and the brain's white matter (WM) is not yet well established. Here, we aim to provide a comprehensive and systematic review of magnetic resonance imaging studies examining the effects of PFA on the WM of the ageing brain. Twenty-nine studies were included in the review: eleven examined WM volume, fourteen WM lesions, and nine WM microstructure. While many studies found that higher levels of PFA were associated with greater WM volumes, reduced volume or severity of WM lesions, or improved measures of WM microstructure, a number of negative findings have also been published. Meta-analyses of global measures of WM volume and WM lesion volume yielded significant, but small, effect sizes. Overall, we found evidence for cautious support of links between PFA and WM structure, and highlighted key areas for future research including the extent to which the relationship between PFA and WM structure is anatomically specific, the influence of possible confounding factors, and the relationship between PFA, WM and cognition

Las buenas maneras

Humans differ substantially in their ability to implicitly extract structural regularities from experience, as required for learning the grammar of a language. The mechanisms underlying this fundamental inter-individual difference, which may determine initial success in language learning, are incompletely understood. Here, we use diffusion tensor magnetic resonance imaging (DTI) to determine white matter integrity around Broca's area, which is crucially involved in both natural and artificial language processing. Twelve young, right-handed individuals completed an artificial grammar learning task, and DTI of their brains were acquired. Inter-individual variability in performance correlated with white matter integrity (increasing fractional anisotropy (FA)) in fibres arising from Broca's area (left BA 44/45), but not from its right-hemispheric homologue. Variability in performance based on superficial familiarity did not show this association. Moreover, when Broca's area was used as a seed mask for probabilistic tractography, we found that mean FA values within the generated tracts was higher in subjects with better grammar learning. Our findings provide the first evidence that integrity of white matter fibre tracts arising from Broca's area is intimately linked with the ability to extract grammatical rules. The relevance of these findings for acquisition of a natural language has to be established in future studies

A systematic review and meta-analysis of cross-sectional studies examining the relationship between mobility and cognition in healthy older adults

Ageing is associated with declines in cognitive function and mobility. The extent to which this relationship encompasses the subdomains of cognition and mobility remains unclear, however. We searched MEDLINE and EMBASE databases for cross-sectional studies examining the association between objective mobility measures (gait, lower-extremity function, balance) and cognitive function (global, executive function, memory, processing speed) in healthy older adults. Of the 642 studies identified, 26 studies met the inclusion criteria, with a total of 26,355 participants. For each feature of physical mobility, the relation to each aspect of cognition was reviewed. In the context of each association, we summarised the results to date and performed random-effects meta-analyses of published data. Reviewed findings suggest that individuals with better mobility perform better on assessments of global cognition, executive function, memory and processing speed. Not all measures of mobility were equally associated with cognitive function, however. Although there was a larger number of gait and lower-extremity function studies, and this may have driven findings, most studies examining balance and cognition measures reported no significant results. Meta-analyses on reported associations supported results by revealing significant, albeit small, effect sizes in favour of a positive association between performance on mobility measures and cognitive assessments. Future research should aim to establish the mechanisms driving this relationship, as this may identify predictors of age-related impairments

Exercise-based cardiac rehabilitation for adults with atrial fibrillation

BACKGROUND:Exercise-based cardiac rehabilitation may benefit adults with atrial fibrillation or those who had been treated for atrial fibrillation. Atrial fibrillation is caused by multiple micro re-entry circuits within the atrial tissue, which result in chaotic rapid activity in the atria. OBJECTIVES:To assess the benefits and harms of exercise-based rehabilitation programmes, alone or with another intervention, compared with no-exercise training controls in adults who currently have AF, or have been treated for AF. SEARCH METHODS:We searched the following electronic databases; CENTRAL and the Database of Abstracts of Reviews of Effectiveness (DARE) in the Cochrane Library, MEDLINE Ovid, Embase Ovid, PsycINFO Ovid, Web of Science Core Collection Thomson Reuters, CINAHL EBSCO, LILACS Bireme, and three clinical trial registers on 14 July 2016. We also checked the bibliographies of relevant systematic reviews identified by the searches. We imposed no language restrictions. SELECTION CRITERIA:We included randomised controlled trials (RCT) that investigated exercise-based interventions compared with any type of no-exercise control. We included trials that included adults aged 18 years or older with atrial fibrillation, or post-treatment for atrial fibrillation. DATA COLLECTION AND ANALYSIS:Two authors independently extracted data. We assessed the risk of bias using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed clinical and statistical heterogeneity by visual inspection of the forest plots, and by using standard Chi² and I² statistics. We performed meta-analyses using fixed-effect and random-effects models; we used standardised mean differences where different scales were used for the same outcome. We assessed the risk of random errors with trial sequential analysis (TSA) and used the GRADE methodology to rate the quality of evidence, reporting it in the 'Summary of findings' table. MAIN RESULTS:We included six RCTs with a total of 421 patients with various types of atrial fibrillation. All trials were conducted between 2006 and 2016, and had short follow-up (eight weeks to six months). Risks of bias ranged from high risk to low risk.The exercise-based programmes in four trials consisted of both aerobic exercise and resistance training, in one trial consisted of Qi-gong (slow and graceful movements), and in another trial, consisted of inspiratory muscle training.For mortality, very low-quality evidence from six trials suggested no clear difference in deaths between the exercise and no-exercise groups (relative risk (RR) 1.00, 95% confidence interval (CI) 0.06 to 15.78; participants = 421; I² = 0%; deaths = 2). Very low-quality evidence from five trials suggested no clear difference between groups for serious adverse events (RR 1.01, 95% CI 0.98 to 1.05; participants = 381; I² = 0%; events = 8). Low-quality evidence from two trials suggested no clear difference in health-related quality of life for the Short Form-36 (SF-36) physical component summary measure (mean difference (MD) 1.96, 95% CI -2.50 to 6.42; participants = 224; I² = 69%), or the SF-36 mental component summary measure (MD 1.99, 95% CI -0.48 to 4.46; participants = 224; I² = 0%). Exercise capacity was assessed by cumulated work, or maximal power (Watt), obtained by cycle ergometer, or by six minute walking test, or ergospirometry testing measuring VO2 peak. We found moderate-quality evidence from two studies that exercise-based rehabilitation increased exercise capacity, measured by VO2 peak, more than no exercise (MD 3.76, 95% CI 1.37 to 6.15; participants = 208; I² = 0%); and very low-quality evidence from four studies that exercise-based rehabilitation increased exercise capacity more than no exercise, measured by the six-minute walking test (MD 75.76, 95% CI 14.00 to 137.53; participants = 272; I² = 85%). When we combined the different assessment tools for exercise capacity, we found very low-quality evidence from six trials that exercise-based rehabilitation increased exercise capacity more than no exercise (standardised mean difference (SMD) 0.86, 95% CI 0.46 to 1.26; participants = 359; I² = 65%). Overall, the quality of the evidence for the outcomes ranged from moderate to very-low. AUTHORS' CONCLUSIONS:Due to few randomised patients and outcomes, we could not evaluate the real impact of exercise-based cardiac rehabilitation on mortality or serious adverse events. The evidence showed no clinically relevant effect on health-related quality of life. Pooled data showed a positive effect on the surrogate outcome of physical exercise capacity, but due to the low number of patients and the moderate to very low-quality of the underpinning evidence, we could not be certain of the magnitude of the effect. Future high-quality randomised trials are needed to assess the benefits and harms of exercise-based cardiac rehabilitation for adults with atrial fibrillation on patient-relevant outcomes

Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex

Magnetic resonance spectroscopy (MRS) allows measurement of neurotransmitter concentrations within a region of interest in the brain. Inter-individual variation in MRS-measured GABA levels have been related to variation in task performance in a number of regions. However, it is not clear how MRS-assessed measures of GABA relate to cortical excitability or GABAergic synaptic activity. We therefore performed two studies investigating the relationship between neurotransmitter levels as assessed by MRS and transcranial magnetic stimulation (TMS) measures of cortical excitability and GABA synaptic activity in the primary motor cortex. We present uncorrected correlations, where the P value should therefore be considered with caution. We demonstrated a correlation between cortical excitability, as assessed by the slope of the TMS input-output curve and MRS-assessed glutamate levels (r = 0.803, P = 0.015) but no clear relationship between MRS-assessed GABA levels and TMS-assessed synaptic GABA(A) activity (2.5 ms inter-stimulus interval (ISI) short-interval intracortical inhibition (SICI); Experiment 1: r = 0.33, P = 0.31; Experiment 2: r = -0.23, P = 0.46) or GABA(B) activity (long-interval intracortical inhibition (LICI); Experiment 1: r = -0.47, P = 0.51; Experiment 2: r = 0.23, P = 0.47). We demonstrated a significant correlation between MRS-assessed GABA levels and an inhibitory TMS protocol (1 ms ISI SICI) with distinct physiological underpinnings from the 2.5 ms ISI SICI (r = -0.79, P = 0.018). Interpretation of this finding is challenging as the mechanisms of 1 ms ISI SICI are not well understood, but we speculate that our results support the possibility that 1 ms ISI SICI reflects a distinct GABAergic inhibitory process, possibly that of extrasynaptic GABA tone

Functional strength training versus movement performance therapy for upper limb motor recovery early after stroke: a RCT

BACKGROUND: Not all stroke survivors respond to the same form of physical therapy in the same way early after stroke. The response is variable and a detailed understanding of the interaction between specific physical therapies and neural structure and function is needed. OBJECTIVES: To determine if upper limb recovery is enhanced more by functional strength training (FST) than by movement performance therapy (MPT), to identify the differences in the neural correlates of response to (1) FST and (2) MPT and to determine whether or not pretreatment neural characteristics can predict recovery in response to (1) FST and (2) MPT. DESIGN: Randomised, controlled, observer-blind, multicentre trial with embedded explanatory investigations. An independent facility used computer-generated randomisation for participants’ group allocation. SETTING: In-patient rehabilitation, participants’ homes, university movement analysis facilities and NHS or university neuroimaging departments in the UK. PARTICIPANTS: People who were between 2 and 60 days after stroke in the territory of the anterior cerebral circulation, with some voluntary muscle contraction in the more affected upper limb but not full function. INTERVENTIONS: Routine rehabilitation [conventional physical therapy (CPT)] plus either MPT or FST in equal doses during a 6-week intervention phase. FST was progressive resistive exercise provided during training of functional tasks. MPT was therapist ‘hands-on’ sensory input and guidance for production of smooth and accurate movement. MAIN OUTCOMES: Action Research Arm Test (ARAT) score for clinical efficacy. Neural measures were made of corticocortical [fractional anisotropy (FA) from corpus callosum midline], corticospinal connectivity (asymmetry of corticospinal tracts FA) and resting motor threshold of paretic biceps brachii (pBB) and extensor carpi radialis muscles (derived from transcranial magnetic stimulation). ANALYSIS: Change in ARAT scores were analysed using analysis of covariance models adjusted for baseline variables and randomisation strata. Correlation coefficients were calculated between change in neural measures and change in ARAT score per group and for the whole sample. An interaction term was calculated for each baseline neural measure and ARAT score change from baseline to outcome. RESULTS: A total of 288 participants were randomised [mean age 72.2 (standard deviation 12.5) years; mean ARAT score of 25.5 (18.2); n = 283]. For the 240 participants with ARAT measurements at baseline and outcome, the mean change scores were FST + CPT = 9.70 (11.72) and MPT + CPT = 7.90 (9.18). The group difference did not reach statistical significance (least squares mean difference 1.35, 95% confidence interval –1.20 to 3.90; p = 0.298). Correlations between ARAT change scores and baseline neural values ranged from –0.147 (p = 0.385) for whole-sample corticospinal connectivity (n = 37) to 0.199 (p = 0.320) for MPT + CPT resting motor threshold pBB (n = 27). No statistically significant interaction effects were found between baseline neural variables and change in ARAT score. There were no differences between groups in adverse events. LIMITATIONS: The number of participants in the embedded explanatory investigation was lower than expected. CONCLUSIONS: The small difference in upper limb improvement in response to FST and MPT did not reach statistical significance. Baseline neural measures neither correlated with upper limb recovery nor predicted therapy response. FUTURE WORK: Needs to continue investigation of the variability of response to specific physical therapies in people early after stroke. TRIAL REGISTRATION: Current Controlled Trials ISRCTN19090862 and National Research Ethics Service reference number 11/EE/0524. FUNDING: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership