Comparing the Impacts of Strain Types on Oxygen-Vacancy Formation in a Perovskite Oxide via Nanometer-Scale Strain Fields.

The utilization of an in-plane lattice misfit in an oxide epitaxially grown on another oxide with a different lattice parameter is a well-known approach to induce strains in oxide materials. However, achieving a sufficiently large misfit strain in this heteroepitaxial configuration is usually challenging, unless the thickness of the grown oxide is kept well below a critical value to prevent the formation of misfit dislocations at the interface for relaxation. Instead of adhering to this conventional approach, here, we employ nanometer-scale large strain fields built around misfit dislocations to examine the effects of two distinct types of strains─tension and compression─on the generation of oxygen vacancies in heteroepitaxial LaCoO3 films. Our atomic-level observations, coupled with local electron-beam irradiation, clarify that the in-plane compression notably suppresses the creation of oxygen vacancies, whereas the formation of vacancies is facilitated under tensile strain. Demonstrating that the defect generation can considerably vary with the type of strain, our study highlights that the experimental approach adopted in this work is applicable to other oxide systems when investigating the strain effects on vacancy formation.

Impact of scleral tunnel length on the position of IOLs in flanged intrascleral haptic fixation.

PURPOSE: To investigate the effect of scleral tunnel length on the effective lens position and tilt of the intraocular lens (IOL) in flanged intrascleral haptic fixation (ISHF) using anterior segment optical coherence tomography (AS-OCT). SETTING: Tertiary institution. DESIGN: Retrospective case-control study. METHODS: This study included 55 and 42 eyes that underwent ISHF with 1.0- and 2.0-mm scleral tunnels, respectively. Twenty-three eyes that underwent sutured fixation were used as a control. The anterior chamber depth (ACD), scleral tunnel length, incident angle of haptic, and tilting of optic were analyzed using AS-OCT. RESULTS: The mean postoperative ACD, vertical tilt angle, and spherical equivalent of the 1.0-mm were 5.27 ± 0.39 mm, 6.04 ± 4.87°, and 0.38 ± 1.03 D, respectively. The ACD and vertical tilt angle of the 1.0-mm were larger than those of the others (p<0.001 and p<0.05, respectively), and the postoperative spherical equivalent was more hyperopic (p<0.05). The 2.0-mm exhibited a lower frequency of tilting greater than 7°. The inter-eye difference in ACD between in-the-bag fixation and ISHF of the1.0-mm tunnel was significantly greater than that in the 2.0-mm tunnel (p<0.05). The 1.0 mm tunnel had a significantly larger incident angle and a longer tunnel length (p<0.001, respectively) and showed a greater difference in the tunnel length on both sides (p<0.05). CONCLUSION: A shorter tunnel yielded a more unstable IOL position, greater variation in angle and tunnel length, and longer ACD during ISHF. An exact 2.0-mm tunnel must be created on both sides to achieve a stable and predictable IOL position.

Effects of bilateral tDCS over DLPFC on response inhibition, craving, and brain functional connectivity in Internet gaming disorder: A randomized, double-blind, sham-controlled trial with fMRI.

Background and aims: Impaired inhibitory control accompanied by enhanced craving is hallmark of addiction. This study investigated the effects of transcranial direct current stimulation (tDCS) on response inhibition and craving in Internet gaming disorder (IGD). We examined the brain changes after tDCS and their correlation with clinical variables. Methods: Twenty-four males with IGD were allocated randomly to an active or sham tDCS group, and data from 22 participants were included for analysis. Participants self-administered bilateral tDCS over the dorsolateral prefrontal cortex (DLPFC) for 10 sessions. Stop-signal tasks were conducted to measure response inhibition and participants were asked about their cravings for Internet gaming at baseline and post-tDCS. Functional magnetic resonance imaging data were collected at pre- and post-tDCS, and group differences in resting-state functional connectivity (rsFC) changes from the bilateral DLPFC and nucleus accumbens were examined. We explored the relationship between changes in the rsFC and behavioral variables in the active tDCS group. Results: A significant group-by-time interaction was observed in response inhibition. After tDCS, only the active group showed a decrease in the stop-signal reaction time (SSRT). Although craving decreased, there were no significant group-by-time interactions or group main effects. The anterior cingulate cortex (ACC) showed group differences in post- versus pre-tDCS rsFC from the right DLPFC. The rsFC between the ACC and left middle frontal gyrus was negatively correlated with the SSRT. Discussion and conclusion: Our study provides preliminary evidence that bilateral tDCS over the DLPFC improves inhibitory control and could serve as a therapeutic approach for IGD.

Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways.

PURPOSE: The respiratory syncytial virus (RSV) is a common respiratory virus that causes acute lower respiratory tract infectious diseases, particularly in young children and older individuals. Activated leukocyte cell adhesion molecule (ALCAM) is a membrane glycoprotein expressed in various cell types, including epithelial cells, and is associated with inflammatory responses and various cancers. However, the precise role of ALCAM in RSV-induced airway inflammation remains unclear, and our study aimed to explore this gap in the literature. METHODS: C57BL/6 wild-type, ALCAM knockout mice and airway epithelial cells were infected with RSV and the expression of ALCAM and inflammatory cytokines were measured. We also conducted further experiments using Anti-ALCAM antibody and recombinant ALCAM in airway epithelial cells. RESULTS: The expression levels of ALCAM and inflammatory cytokines increased in both RSV-infected mice and airway epithelial cells. Interestingly, IL-33 expression was significantly reduced in ALCAM-knockdown cells compared to control cells following RSV infection. Anti-ALCAM antibody treatment also reduced IL-33 expression following RSV infection. Furthermore, the phosphorylation of ERK1/2, p38, and JNK was diminished in ALCAM-knockdown cells compared to control cells following RSV infection. Notably, in the control cells, inhibition of these pathways significantly decreased the expression of IL-33. In vivo study also confirmed a reduction in inflammation induced by RSV infection in ALCAM deficient mice compared to wild-type mice. CONCLUSION: These findings demonstrate that ALCAM contributes to RSV-induced airway inflammation at least partly by influencing IL-33 expression through mitogen-activated protein kinase signaling pathways. These results suggest that targeting ALCAM could be a potential therapeutic strategy for alleviating IL-33-associated lung diseases.

Brain connectome correlates of short-term motor learning in healthy older subjects.

The motor learning process entails plastic changes in the brain, especially in brain network reconfigurations. In the current study, we sought to characterize motor learning by determining changes in the coupling behaviour between the brain functional and structural connectomes on a short timescale. 39 older subjects (age: mean (SD) = 69.7 (4.7) years, men:women = 15:24) were trained on a visually guided sequential hand grip learning task. The brain structural and functional connectomes were constructed from diffusion-weighted MRI and resting-state functional MRI, respectively. The association of motor learning ability with changes in network topology of the brain functional connectome and changes in the correspondence between the brain structural and functional connectomes were assessed. Motor learning ability was related to decreased efficiency and increased modularity in the visual, somatomotor, and frontoparietal networks of the brain functional connectome. Between the brain structural and functional connectomes, reduced correspondence in the visual, ventral attention, and frontoparietal networks as well as the whole-brain network was related to motor learning ability. In addition, structure-function correspondence in the dorsal attention, ventral attention, and frontoparietal networks before motor learning was predictive of motor learning ability. These findings indicate that, in the view of brain connectome changes, short-term motor learning is represented by a detachment of the brain functional from the brain structural connectome. The structure-function uncoupling accompanied by the enhanced segregation into modular structures over the core functional networks involved in the learning process may suggest that facilitation of functional flexibility is associated with successful motor learning.

CONTRIBUTION FACTORS OF EFFECTIVE LENS POSITION, TILT, AND DECENTRATION DURING FLANGED SCLERAL FIXATION OF INTRAOCULAR LENS: A Model Eye Study.

PURPOSE: The authors aimed to elucidate the factors related to effective lens position, tilt, and decentration of scleral fixed intraocular lenses (IOLs) with a flanged haptic technique in an artificial eye model using anterior segment optical coherence tomography. METHODS: Two bent 27-gauge needles were passed through a 1.0- or 2.0-mm scleral tunnel, 2.0 mm posterior to the limbus and 180° apart. Both haptics of a three-piece IOL were docked with guide needles and externalized. Factors related to the IOL position were analyzed using anterior segment optical coherence tomography and a stereomicroscope. RESULTS: The 1.0-mm scleral tunnel induced a significantly longer effective lens position than the 2.0-mm tunnel and suture fixation ( P < 0.05 and P < 0.01, respectively). Discrepancy in scleral tunnel length induced higher decentration of the optic to the opposite side of the haptic-embedded shorter tunnel and tilt perpendicular to the fixed axis than that in the scleral tunnel of the same length ( P < 0.001 and P < 0.05, respectively). If the scleral fixation points of both haptics are not exactly 180° apart, the IOL may become decentered and tilted ( P < 0.01 and P < 0.05, respectively). CONCLUSION: In the flanged haptic technique, the length, balance, and position of both scleral tunnels determine IOL effective lens position, tilt, and decentration.

Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning.

The stimulation of deep brain structures has thus far only been possible with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here we show successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, functional magnetic resonance imaging studies and behavioral evaluations. Theta-burst patterned striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor performance, especially in healthy older participants as they have lower natural learning skills than younger subjects. These findings place tTIS as an exciting new method to target deep brain structures in humans noninvasively, thus enhancing our understanding of their functional role. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders in which deep striatal structures play key pathophysiological roles.

Machine Learning-assisted Quantitative Mapping of Intracortical Axonal Plasticity Following a Focal Cortical Stroke in Rodents.

Stroke destroys neurons and their connections leading to focal neurological deficits. Although limited, many patients exhibit a certain degree of spontaneous functional recovery. Structural remodeling of the intracortical axonal connections is implicated in the reorganization of cortical motor representation maps, which is considered to be an underlying mechanism of the improvement in motor function. Therefore, an accurate assessment of intracortical axonal plasticity would be necessary to develop strategies to facilitate functional recovery following a stroke. The present study developed a machine learning-assisted image analysis tool based on multi-voxel pattern analysis in fMRI imaging. Intracortical axons originating from the rostral forelimb area (RFA) were anterogradely traced using biotinylated dextran amine (BDA) following a photothrombotic stroke in the mouse motor cortex. BDA-traced axons were visualized in tangentially sectioned cortical tissues, digitally marked, and converted to pixelated axon density maps. Application of the machine learning algorithm enabled sensitive comparison of the quantitative differences and the precise spatial mapping of the post-stroke axonal reorganization even in the regions with dense axonal projections. Using this method, we observed a substantial extent of the axonal sprouting from the RFA to the premotor cortex and the peri-infarct region caudal to the RFA. Therefore, the machine learningassisted quantitative axonal mapping developed in this study can be utilized to discover intracortical axonal plasticity that may mediate functional restoration following stroke.

Characteristics of perivascular space dilatation in normal aging.

The increased incidence of dilated perivascular spaces (dPVSs) visible on MRI has been observed with advancing age, but the relevance of PVS dilatation to normal aging across the lifespan has yet to be fully clarified. In the current study, we sought to find out the age dependence of dPVSs by exploring changes in different characteristics of PVS dilatation across a wide range of age. For 1220 healthy subjects aged between 18 and 100 years, PVSs were automatically segmented and characteristics of PVS dilatation were assessed in terms of the burden, location, and morphology of PVSs in the white matter (WM) and basal ganglia (BG). A machine learning model using the random forests method was constructed to estimate the subjects' age by employing the PVS features. The constructed machine learning model was able to estimate the age of the subjects with an error of 9.53 years on average (correlation = 0.875). The importance of the PVS features indicated the primary contribution of the burden of PVSs in the BG and the additional contribution of locational and morphological changes of PVSs, specifically peripheral extension and reduced linearity, in the WM to age estimation. Indeed, adding the PVS location or morphology features to the PVS burden features provided an improvement to the performance of age estimation. The age dependence of dPVSs in terms of such various characteristics of PVS dilatation in healthy subjects could provide a more comprehensive reference for detecting brain disease-related PVS dilatation.

Early motor skill acquisition in healthy older adults: brain correlates of the learning process.

Motor skill learning is a crucial process at all ages. However, healthy aging is often accompanied by a reduction in motor learning capabilities. This study characterized the brain dynamics of healthy older adults during motor skill acquisition and identified brain regions associated with changes in different components of performance. Forty-three subjects participated in a functional magnetic resonance imaging study during which they learned a sequential grip force modulation task. We evaluated the continuous changes in brain activation during practice as well as the continuous performance-related changes in brain activation. Practice of the motor skill was accompanied by increased activation in secondary motor and associative areas. In contrast, visual and frontal areas were less recruited as task execution progressed. Subjects showed significant improvements on the motor skill. While faster execution relied on parietal areas and was inversely associated with frontal activation, accuracy was related to activation in primary and secondary motor areas. Better performance was achieved by the contribution of parietal regions responsible for efficient visuomotor processing and cortical motor regions involved in the correct action selection. The results add to the understanding of online motor learning in healthy older adults, showing complementary roles of specific networks for implementing changes in precision and speed.

Stratified predictions of upper limb motor outcomes after stroke.

Introduction: Longitudinal observations of upper limb motor recovery after stroke have suggested that certain subgroups may exhibit distinct recovery patterns. Here we sought to examine whether the predictive ability for post-stroke upper limb motor outcomes could be enhanced by applying conventional stratification strategies. Method: For 60 individuals who suffered the first stroke, upper limb motor impairment was assessed with the upper extremity Fugl-Meyer assessment (UE-FMA) at 2 weeks as a baseline and then 3 months post-stroke. Brain structural damage at baseline was assessed by MRI data-derived markers ranging from traditional lesion size to the lesion load and to the disconnectome. Linear regression models for predicting upper limb motor outcomes (UE-FMA score at 3 months post-stroke) based on baseline upper limb motor impairment (UE-FMA score at 2 weeks post-stroke), brain structural damage, and their combinations were generated, and those with the best predictive performance were determined for individual subgroups stratified according to initial impairment (severe and non-severe), lesion location (cortical and non-cortical), and neurophysiological status (motor evoked potential-positive and motor evoked potential-negative). Results: The best predictions were made by baseline upper limb motor impairment alone for subgroups with less functional impairment (non-severe) or less structural involvement (non-cortical), but by the combination of baseline upper limb motor impairment and brain structural damage for the other subgroups. The predictive models tailored for subgroups determined according to initial impairment and neurophysiological status yielded a smaller overall error than that for the whole group in upper limb motor outcome predictions. Discussion: The predictive ability for upper limb motor outcomes could be enhanced beyond the one-size-fits-all model for all individuals with stroke by applying specific stratification strategies, with stratification according to initial impairment being the most promising. We expect that predictive models tailored for individual subgroups could lead closer to the personalized prognosis of upper limb motor outcomes after stroke.

Scrambler Therapy for Chronic Pain after Burns and Its Effect on the Cerebral Pain Network: A Prospective, Double-Blinded, Randomized Controlled Trial.

Chronic pain is common after burn injuries, and post-burn neuropathic pain is the most important complication that is difficult to treat. Scrambler therapy (ST) is a non-invasive modality that uses patient-specific electrocutaneous nerve stimulation and is an effective treatment for many chronic pain disorders. This study used magnetic resonance imaging (MRI) to evaluate the pain network-related mechanisms that underlie the clinical effect of ST in patients with chronic burn-related pain. This prospective, double-blinded, randomized controlled trial (ClinicalTrials.gov: NCT03865693) enrolled 43 patients who were experiencing chronic neuropathic pain after unilateral burn injuries. The patients had moderate or greater chronic pain (a visual analogue scale (VAS) score of ≥5), despite treatment using gabapentin and other physical modalities, and were randomized 1:1 to receive real or sham ST sessions. The ST was performed using the MC5-A Calmare device for ten 45 min sessions (Monday to Friday for 2 weeks). Baseline and post-treatment parameters were evaluated subjectively using the VAS score for pain and the Hamilton Depression Rating Scale; MRI was performed to identify objective central nervous system changes by measuring the cerebral blood volume (CBV). After 10 ST sessions (two weeks), the treatment group exhibited a significant reduction in pain relative to the sham group. Furthermore, relative to the pre-ST findings, the post-ST MRI evaluations revealed significantly decreased CBV in the orbito-frontal gyrus, middle frontal gyrus, superior frontal gyrus, and gyrus rectus. In addition, the CBV was increased in the precentral gyrus and postcentral gyrus of the hemisphere associated with the burned limb in the ST group, as compared with the CBV of the sham group. Thus, a clinical effect from ST on burn pain was observed after 2 weeks, and a potential mechanism for the treatment effect was identified. These findings suggest that ST may be an alternative strategy for managing chronic pain in burn patients.

Evaluating reproducibility and subject-specificity of microstructure-informed connectivity.

Tractography enables identifying and evaluating the healthy and diseased brain's white matter pathways from diffusion-weighted magnetic resonance imaging data. As previous evaluation studies have reported significant false-positive estimation biases, recent microstructure-informed tractography algorithms have been introduced to improve the trade-off between specificity and sensitivity. However, a major limitation for characterizing the performance of these techniques is the lack of ground truth brain data. In this study, we compared the performance of two relevant microstructure-informed tractography methods, SIFT2 and COMMIT, by assessing the subject specificity and reproducibility of their derived white matter pathways. Specifically, twenty healthy young subjects were scanned at eight different time points at two different sites. Subject specificity and reproducibility were evaluated using the whole-brain connectomes and a subset of 29 white matter bundles. Our results indicate that although the raw tractograms are more vulnerable to the presence of false-positive connections, they are highly reproducible, suggesting that the estimation bias is subject-specific. This high reproducibility was preserved when microstructure-informed tractography algorithms were used to filter the raw tractograms. Moreover, the resulting track-density images depicted a more uniform coverage of streamlines throughout the white matter, suggesting that these techniques could increase the biological meaning of the estimated fascicles. Notably, we observed an increased subject specificity by employing connectivity pre-processing techniques to reduce the underlaying noise and the data dimensionality (using principal component analysis), highlighting the importance of these tools for future studies. Finally, no strong bias from the scanner site or time between measurements was found. The largest intraindividual variance originated from the sole repetition of data measurements (inter-run).

Simulating the progression of brain structural alterations in Parkinson's disease.

Considering brain structural alterations as neurodegenerative consequences of Parkinson's disease (PD), we sought to infer the progression of PD via the ordering of brain structural alterations from cross-sectional MRI observations. Having measured cortical thinning in gray matter (GM) regions and disintegrity in white matter (WM) regions as MRI markers of structural alterations for 130 patients with PD (69 ± 10 years, 72 men), stochastic simulation based on the probabilistic relationship between the brain regions was conducted to infer the ordering of structural alterations across all brain regions and the staging of structural alterations according to changes in clinical status. The ordering of structural alterations represented WM disintegrity tending to occur earlier than cortical thinning. The staging of structural alterations indicated structural alterations happening mostly before major disease complications such as postural instability and dementia. Later disease states predicted by the sequence of structural alterations were significantly related to more severe clinical symptoms. The relevance of the ordering of brain structural alterations to the severity of clinical symptoms suggests the clinical feasibility of predicting PD progression states.

Predicting superagers by machine learning classification based on the functional brain connectome using resting-state functional magnetic resonance imaging.

Superagers are defined as older adults who have youthful memory performance comparable to that of middle-aged adults. Classifying superagers based on the brain connectome using machine learning modeling can provide important insights on the physiology underlying successful aging. We aimed to investigate the unique patterns of functional brain connectome of superagers and develop predictive models to differentiate superagers from typical agers based on machine learning methods. We obtained resting-state functional magnetic resonance imaging (rsfMRI) data and cognitive measures from 32 superagers and 58 typical agers. The accuracies of three machine learning methods including the linear support vector machine classifier (SV), the random forest classifier (RF), and the logistic regression classifier (LR) in predicting superagers were comparable (SV = 0.944, RF = 0.944, LR = 0.944); however, RF achieved the highest area under the curve (AUC; 0.979). An ensemble learning method combining the three classifiers achieved the highest AUC (0.986). The most discriminative nodes for predicting superagers encompassed areas in the precuneus; posterior cingulate gyrus; insular cortex; and superior, middle, and inferior frontal gyrus, which were located in default, salient, and multiple-demand networks. Thus, rsfMRI data can provide high accuracy for predicting superagers, thereby capturing and describing the unique characteristics of their functional brain connectome.

The predictive value of lesion and disconnectome loads for upper limb motor impairment after stroke.

OBJECTIVE: The putative effect of lesion-induced brain damage on post-stroke upper limb motor impairment can be estimated by overlaying a patient's lesion or its surrogate with key motor areas. We assessed the predictive value of imaging-based brain damage measures for cross-sectional upper limb motor impairment and subsequent upper limb motor outcome after stroke. METHODS: In 47 stroke patients, upper limb motor impairment was evaluated with the Upper-Extremity Fugl-Meyer Assessment (UE-FMA) at 2 weeks (2W) and 3 months (3M) post-stroke. Given each patient's lesion identified at 2W, we considered the disconnectome, estimated as an ensemble of structural and functional connections passing through the lesion, as a surrogate of the lesion. The lesion load and the disconnectome load were measured by overlaying the lesion and disconnectome with the corticospinal tract (CST) and motor cortex (MC), and their association with the UE-FMA score at 2W and 3M was assessed. RESULTS: Whereas the disconnectome loads on the CST and MC were better in predicting the UE-FMA score at 2W, the lesion load on the CST was better in predicting the UE-FMA score at 3M. Furthermore, when the CST lesion load was combined with the UE-FMA score at 2W, the UE-FMA score at 3M was better predicted, with smaller generalization error, than by using either measure alone. CONCLUSIONS: The combination of the CST lesion load and baseline upper limb motor impairment would provide a tailored fusion of imaging and clinical measures for more accurate motor outcome prediction.

Variability and reproducibility of multi-echo T2 relaxometry: Insights from multi-site, multi-session and multi-subject MRI acquisitions.

Quantitative magnetic resonance imaging (qMRI) can increase the specificity and sensitivity of conventional weighted MRI to underlying pathology by comparing meaningful physical or chemical parameters, measured in physical units, with normative values acquired in a healthy population. This study focuses on multi-echo T2 relaxometry, a qMRI technique that probes the complex tissue microstructure by differentiating compartment-specific T2 relaxation times. However, estimation methods are still limited by their sensitivity to the underlying noise. Moreover, estimating the model's parameters is challenging because the resulting inverse problem is ill-posed, requiring advanced numerical regularization techniques. As a result, the estimates from distinct regularization strategies are different. In this work, we aimed to investigate the variability and reproducibility of different techniques for estimating the transverse relaxation time of the intra- and extra-cellular space (T2IE) in gray (GM) and white matter (WM) tissue in a clinical setting, using a multi-site, multi-session, and multi-run T2 relaxometry dataset. To this end, we evaluated three different techniques for estimating the T2 spectra (two regularized non-negative least squares methods and a machine learning approach). Two independent analyses were performed to study the effect of using raw and denoised data. For both the GM and WM regions, and the raw and denoised data, our results suggest that the principal source of variance is the inter-subject variability, showing a higher coefficient of variation (CoV) than those estimated for the inter-site, inter-session, and inter-run, respectively. For all reconstruction methods studied, the CoV ranged between 0.32 and 1.64%. Interestingly, the inter-session variability was close to the inter-scanner variability with no statistical differences, suggesting that T2IE is a robust parameter that could be employed in multi-site neuroimaging studies. Furthermore, the three tested methods showed consistent results and similar intra-class correlation (ICC), with values superior to 0.7 for most regions. Results from raw data were slightly more reproducible than those from denoised data. The regularized non-negative least squares method based on the L-curve technique produced the best results, with ICC values ranging from 0.72 to 0.92.

Cerebellar White Matter Abnormalities in Charcot-Marie-Tooth Disease: A Combined Volumetry and Diffusion Tensor Imaging Analysis.

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous hereditary peripheral neuropathy. Brain volumetry and diffusion tensor imaging (DTI) were performed in 47 controls and 47 CMT patients with PMP22 duplication (n = 10), MFN2 (n = 15), GJB1 (n = 11), or NEFL mutations (n = 11) to investigate for structural changes in the cerebellum. Volume of cerebellar white matter (WM) was significantly reduced in CMT patients with NEFL mutations. Abnormal DTI findings were observed in the superior, middle, and inferior cerebellar peduncles, predominantly in NEFL mutations and partly in GJB1 mutations. Cerebellar ataxia was more prevalent in the NEFL mutation group (72.7%) than the GJB1 mutation group (9.1%) but was not observed in other genotypic subtypes, which indicates that structural cerebellar abnormalities were associated with the presence of cerebellar ataxia. However, NEFL and GJB1 mutations did not affect cerebellar gray matter (GM), and neither cerebellar GM nor WM abnormalities were observed in the PMP22 duplication or MFN2 mutation groups. We found structural evidence of cerebellar WM abnormalities in CMT patients with NEFL and GJB1 mutations and an association between cerebellar WM involvement and cerebellar ataxia in these genetic subtypes, especially in the NEFL subgroup. Therefore, we suggest that neuroimaging, such as MRI volumetry or DTI, for CMT patients could play an important role in detecting abnormalities of cerebellar WM.

Plastic Changes in Pain and Motor Network Induced by Chronic Burn Pain.

Musculoskeletal diseases with chronic pain are difficult to control because of their association with both central as well as the peripheral nervous system. In burn patients, chronic pain is one of the major complications that cause persistent discomfort. The peripheral mechanisms of chronic pain by burn have been greatly revealed through studies, but the central mechanisms have not been identified. Our study aimed to characterize the cerebral plastic changes secondary to electrical burn (EB) and non-electrical burn (NEB) by measuring cerebral blood volume (CBV). Sixty patients, twenty with electrical burn (EB) and forty with non-electrical burn (NEB), having chronic pain after burn, along with twenty healthy controls, participated in the study. Voxel-wise comparisons of relative CBV maps were made among EB, NEB, and control groups over the entire brain volume. The CBV was measured as an increase and decrease in the pain and motor network including postcentral gyrus, frontal lobe, temporal lobe, and insula in the hemisphere associated with burned limbs in the whole burn group. In the EB group, CBV was decreased in the frontal and temporal lobes in the hemisphere associated with the burned side. In the NEB group, the CBV was measured as an increase or decrease in the pain and motor network in the postcentral gyrus, precentral gyrus, and frontal lobe of the hemisphere associated with the burn-affected side. Among EB and NEB groups, the CBV changes were not different. Our findings provide evidence of plastic changes in pain and motor network in patients with chronic pain by burn.

The structural connectome and motor recovery after stroke: predicting natural recovery.

Stroke patients vary considerably in terms of outcomes: some patients present 'natural' recovery proportional to their initial impairment (fitters), while others do not (non-fitters). Thus, a key challenge in stroke rehabilitation is to identify individual recovery potential to make personalized decisions for neuro-rehabilitation, obviating the 'one-size-fits-all' approach. This goal requires (i) the prediction of individual courses of recovery in the acute stage; and (ii) an understanding of underlying neuronal network mechanisms. 'Natural' recovery is especially variable in severely impaired patients, underscoring the special clinical importance of prediction for this subgroup. Fractional anisotropy connectomes based on individual tractography of 92 patients were analysed 2 weeks after stroke (TA) and their changes to 3 months after stroke (TC - TA). Motor impairment was assessed using the Fugl-Meyer Upper Extremity (FMUE) scale. Support vector machine classifiers were trained to separate patients with natural recovery from patients without natural recovery based on their whole-brain structural connectomes and to define their respective underlying network patterns, focusing on severely impaired patients (FMUE < 20). Prediction accuracies were cross-validated internally, in one independent dataset and generalized in two independent datasets. The initial connectome 2 weeks after stroke was capable of segregating fitters from non-fitters, most importantly among severely impaired patients (TA: accuracy = 0.92, precision = 0.93). Secondary analyses studying recovery-relevant network characteristics based on the selected features revealed (i) relevant differences between networks contributing to recovery at 2 weeks and network changes over time (TC - TA); and (ii) network properties specific to severely impaired patients. Important features included the parietofrontal motor network including the intraparietal sulcus, premotor and primary motor cortices and beyond them also attentional, somatosensory or multimodal areas (e.g. the insula), strongly underscoring the importance of whole-brain connectome analyses for better predicting and understanding recovery from stroke. Computational approaches based on structural connectomes allowed the individual prediction of natural recovery 2 weeks after stroke onset, especially in the difficult to predict group of severely impaired patients, and identified the relevant underlying neuronal networks. This information will permit patients to be stratified into different recovery groups in clinical settings and will pave the way towards personalized precision neurorehabilitative treatment.