It is demonstrated that the application of piezoelectric sensors to metallic bars and strands can enable determining the status of the integrity of these elements through the spectrum of their ...acoustic excitations. The voltage output of the piezo, secured to metal bars or strands, is fed to the input of a Fast Fourier Transform analyzer, which allows displaying the spectrum of the excitations from which information on the length, overall quality of the metal, and the presence of defects can be obtained. We show that the analysis, performed on several materials and strands of different lengths, could be useful for cases in which visible inspection and/or direct access to the entire body of the metallic elements is not possible. Applications of our study for testing metallic structures embedded in concrete foundations are reported for construction sites.
Memory loss is one of the first symptoms of typical Alzheimer's disease (AD), for which there are no effective therapies available. The precuneus (PC) has been recently emphasized as a key area for ...the memory impairment observed in early AD, likely due to disconnection mechanisms within large-scale networks such as the default mode network (DMN). Using a multimodal approach we investigated in a two-week, randomized, sham-controlled, double-blinded trial the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the PC on cognition, as measured by the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite in 14 patients with early AD (7 females). TMS combined with electroencephalography (TMS-EEG) was used to detect changes in brain connectivity. We found that rTMS of the PC induced a selective improvement in episodic memory, but not in other cognitive domains. Analysis of TMS-EEG signal revealed an increase of neural activity in patients' PC, an enhancement of brain oscillations in the beta band and a modification of functional connections between the PC and medial frontal areas within the DMN.
Our findings show that high-frequency rTMS of the PC is a promising, non-invasive treatment for memory dysfunction in patients at early stages of AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD.
•The precuneus is a key area for memory impairment in Alzheimer’s disease (AD).•We investigated the effects of precuneus-rTMS on memory in patients with early AD.•Precuneus-rTMS induced a selective improvement in episodic memory.•Precuneus-rTMS enhance precuneus activity and connectivity with frontal areas.•Precuneus-rTMS is a promising treatment for memory dysfunction in early AD patients.
Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, ...specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analyzed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology.
Network models based on structural connectivity have been increasingly used as the blueprint for large-scale simulations of the human brain. As the nodes of this network are distributed through the ...cortex and interconnected by white matter pathways with different characteristics, modeling the associated conduction delays becomes important. The goal of this study is to estimate and characterize these delays directly from the brain structure. To achieve this, we leveraged microstructural measures from a combination of advanced magnetic resonance imaging acquisitions and computed the main determinants of conduction velocity, namely axonal diameter and myelin content. Using the model proposed by Rushton, we used these measures to calculate the conduction velocity and estimated the associated delays using tractography. We observed that both the axonal diameter and conduction velocity distributions presented a rather constant trend across different connection lengths, with resulting delays that scale linearly with the connection length. Relying on insights from graph theory and Kuramoto simulations, our results support the approximation of constant conduction velocity but also show path- and region-specific differences.
Systemic sclerosis (scleroderma) is characterized by immunologic abnormalities, injury of endothelial cells, and tissue fibrosis. Abnormal oxidative stress has been documented in scleroderma and ...linked to fibroblast activation. Since platelet-derived growth factor (PDGF) stimulates the production of reactive oxygen species (ROS) and since IgG from patients with scleroderma reacts with human fibroblasts, we tested the hypothesis that patients with scleroderma have serum autoantibodies that stimulate the PDGF receptor (PDGFR), activating collagen-gene expression.
We analyzed serum from 46 patients with scleroderma and 75 controls, including patients with other autoimmune diseases, for stimulatory autoantibodies to PDGFR by measuring the production of ROS produced by the incubation of purified IgG with mouse-embryo fibroblasts carrying inactive copies of PDGFR alpha or beta chains or the same cells expressing PDGFR alpha or beta. Generation of ROS was assayed with and without specific PDGFR inhibitors. Antibodies were characterized by immunoprecipitation, immunoblotting, and absorption experiments.
Stimulatory antibodies to the PDGFR were found in all the patients with scleroderma. The antibodies recognized native PDGFR, inducing tyrosine phosphorylation and ROS accumulation. Autoantibody activity was abolished by preincubation with cells expressing the PDGFR alpha chain or with recombinant PDGFR or by PDGFR tyrosine kinase inhibitors. Stimulatory PDGFR antibodies selectively induced the Ha-Ras-ERK1/2 and ROS cascades and stimulated type I collagen-gene expression and myofibroblast phenotype conversion in normal human primary fibroblasts.
Stimulatory autoantibodies against PDGFR appear to be a specific hallmark of scleroderma. Their biologic activity on fibroblasts strongly suggests that they have a causal role in the pathogenesis of the disease.
Microstructural imaging and connectomics are two research areas that hold great potential for investigating brain structure and function. Combining these two approaches can lead to a better and more ...complete characterization of the brain as a network. The aim of this work is characterizing the connectome from a novel perspective using the myelination measure given by the g-ratio. The g-ratio is the ratio of the inner to the outer diameters of a myelinated axon, whose aggregated value can now be estimated in vivo using MRI. In two different datasets of healthy subjects, we reconstructed the structural connectome and then used the g-ratio estimated from diffusion and magnetization transfer data to characterize the network structure. Significant characteristics of g-ratio weighted graphs emerged. First, the g-ratio distribution across the edges of the graph did not show the power-law distribution observed using the number of streamlines as a weight. Second, connections involving regions related to motor and sensory functions were the highest in myelin content. We also observed significant differences in terms of the hub structure and the rich-club organization suggesting that connections involving hub regions present higher myelination than peripheral connections. Taken together, these findings offer a characterization of g-ratio distribution across the connectome in healthy subjects and lay the foundations for further investigating plasticity and pathology using a similar approach.
•We integrated myelination into the structural connectome using the g-ratio.•The average g-ratio and the number of streamlines follow different patterns.•A myelin blueprint can be observed looking at the hub structure.•The anatomical organization follows patterns consistent with existing literature.
Ex vivo imaging enables analysis of the human brain at a level of detail that is not possible in vivo with MRI. In particular, histology can be used to study brain tissue at the microscopic level, ...using a wide array of different stains that highlight different microanatomical features. Complementing MRI with histology has important applications in ex vivo atlas building and in modeling the link between microstructure and macroscopic MR signal. However, histology requires sectioning tissue, hence distorting its 3D structure, particularly in larger human samples. Here, we present an open-source computational pipeline to produce 3D consistent histology reconstructions of the human brain. The pipeline relies on a volumetric MRI scan that serves as undistorted reference, and on an intermediate imaging modality (blockface photography) that bridges the gap between MRI and histology. We present results on 3D histology reconstruction of whole human hemispheres from two donors.
Since early days after stroke, the brain undergoes a complex reorganization to allow compensatory mechanisms that promote functional recovery. However, these mechanisms are still poorly understood ...and there is urgent need to identify neurophysiological markers of functional recovery after stroke. Here we aimed to track longitudinally the time-course of cortical reorganization by measuring for the first time EEG cortical activity evoked by TMS pulses in patients with subcortical stroke.
Thirteen patients in the sub-acute phase of ischemic subcortical stroke with motor symptoms completed the longitudinal study, being evaluated within 20 days and after 40, 60 and 180 days after stroke onset. For each time-point, EEG cortical activity evoked by single TMS pulses was assessed over the motor and parietal cortex of the affected and unaffected hemisphere. We evaluated global TMS-evoked activity and TMS-evoked oscillations in different frequency bands. These measurements were paralleled with clinical and behavioral assessment.
We found that motor cortical activity measured by TMS-EEG varied across time in the affected hemisphere. An increase of TMS-evoked activity was evident at 40 days after stroke onset. Moreover, stroke patients showed a significant increase in TMS-evoked alpha oscillations, as highlighted performing analysis in the time-frequency domain. Notably, these changes indicated that crucial mechanisms of cortical reorganization occur in this short-time window. These changes coincided with the clinical improvement. TMS-evoked alpha oscillatory activity recorded at baseline was associated to better functional recovery at 40 and 60 days' follow-up evaluations, suggesting that the power of the alpha rhythm can be considered a good predictor of motor recovery. This study demonstrates that cortical activity increases dynamically in the early phases of recovery after stroke in the affected hemisphere. These findings point to TMS-evoked alpha oscillatory activity as a potential neurophysiological markers of stroke recovery and could be helpful to determine the temporal window in which neuromodulation should be potentially able to drive neuroplasticity in an effective functional direction.
•Complex cortical reorganization occurs after stroke onset.•TMS-evoked activity represents a direct measure of cortical organization.•TMS-EEG measurements are able to track longitudinally motor recovery following stroke.
Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 ...can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in the Eyes" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' "Theory of Mind-network", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life.
Behavioral and psychological symptoms of dementia (BPSD) are commonly observed since the early stage of Alzheimer's disease (AD) associated with structural brain changes. It is conceivable that they ...may also relate to functional brain changes. This resting-state functional MRI (RS-fMRI) study investigated the alterations within functional brain networks of a cohort of AD patients at different clinical stages who presented with BPSD. One hundred one AD patients and 56 patients with amnestic mild cognitive impairment underwent a neuropsychological evaluation including the Neuropsychiatry Inventory-12 (NPI-12). All patients and 35 healthy controls (HS) underwent 3T-MRI. Factor analysis was used to extract the principal factors from NPI-12, while RS-fMRI data were processed using graph theory to investigate functional connectivity. Five factors were extracted from NPI-12. Sixty-two percent of patients showed BPSD and functional brain connectivity changes in various networks compared to those without BPSD and HS. These changes contributed to account for patients' BPSD. This work opens new perspectives in terms of nonpharmacological interventions that might be designed to modulate brain connectivity and improve patients' BPSD.
•Behavioral and psychological symptoms of dementia (BPSD) are observed since early stage of Alzheimer's disease.•BPSD are grouped in main factors.•Patients with BPSD show changes in brain functional connectivity.•Different factors associate with reduced brain functional connectivity in different networks.•This has potential implications for nonpharmacological interventions.
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