M1 Region Research Articles

Effect of rTMS intervention on upper limb motor function after stroke: A study based on fNIRS.

Stroke is a disease with a high fatality rate worldwide and a major cause of long-term disability. In the rehabilitation of limb motor function after stroke, the rehabilitation of upper limb function takes a long time and the recovery progress is slow, which seriously affects the patients' self-care ability in daily life. Repeated transcranial magnetic stimulation (rTMS) has been increasingly used to improve limb dysfunction in patients with stroke. However, a standardized reference for selecting a magnetic stimulation regimen is not available. Whether to increase the inhibition of the contralateral hemispheric motor cortex remains controversial. This study has evaluated the effects of different rTMS stimulation programs on upper limb function and corresponding brain functional network characteristics of patients with stroke and sought a new objective standard based on changes in brain network parameters to guide accurate rTMS stimulation programs. Thirty-six patients with stroke were selected and divided into control group and treatment group by number table method, with 18 patients in each group, and 3 patients in the control group were turned out and lost due to changes in disease condition. The treatment group was divided into two groups. TMS1 group was given 1 Hz magnetic stimulation in the M1 region of the contralesional hemisphere +10 Hz magnetic stimulation in the M1 region of the affected hemisphere, and the TMS2 group was given 10 Hz magnetic stimulation in the M1 region of the affected hemisphere. The control group was given false stimulation. The treatment course was once a day for 5 days a week for 4 weeks. The Fugl-Meyer Assessment for upper extremity (FMA-UE) sand near-infrared brain function were collected before treatment, 2 weeks after treatment, and 4 weeks after treatment, and the brain function network was constructed. Changes in brain oxygenated hemoglobin concentration and brain network parameters were analyzed with the recovery of motor function (i.e., increased FMA score). Meanwhile, according to the average increment of brain network parameters, the rTMS stimulation group was divided into two groups with good efficacy and poor efficacy. Network parameters of the two groups before and after rTMS treatment were analyzed statistically. (1) Before treatment, there was no statistical difference in Fugl-Meyer score between the control group and the magnetic stimulation group (p = 0.178).Compared with before treatment, Fugl-Meyer scores of 2 and 4 weeks after treatment were significantly increased in both groups (p <0.001), and FMA scores of 4 weeks after treatment were significantly improved compared with 2 weeks after treatment (p < 0.001). FMA scores increased faster in the magnetic stimulation group at 2 and 4 weeks compared with the control group at the same time point (p <0.001).TMS1 and TMS2 were compared at the same time point, FMA score in TMS2 group increased more significantly after 4 weeks of treatment (p = 0.010). (2) Before treatment, HbO2 content in healthy sensory motor cortex (SMC) area of magnetic stimulation group and control group was higher than that in other region of interest (ROI) area, but there was no significant difference in ROI between the two groups. After 4 weeks of treatment, the HbO2 content in the healthy SMC area was significantly decreased (p < 0.001), while the HbO2 content in the affected SMC area was significantly increased, and the change was more significant in the magnetic stimulation group (p < 0.001). (3) In-depth study found that with the recovery of motor function (FMA upper limb score increase ≥4 points) after magnetic stimulation intervention, brain network parameters were significantly improved. The mean increment of network parameters in TMS1 group and TMS2 group was significantly different (χ 2 = 5.844, p = 0.016). TMS2 group was more advantageous than TMS1 group in improving the mean increment of brain network parameters. (1) The rTMS treatment is beneficial to the recovery of upper limb motor function in stroke patients, and can significantly improve the intensity of brain network connection and reduce the island area. The island area refers to an isolated activated brain area that cannot transmit excitation to other related brain areas. (2) When the node degree of M1_Healthy region less than 0.52, it is suggested to perform promotion therapy only in the affected hemisphere. While the node degree greater than 0.52, and much larger than that in the M1_affected region. it is suggested that both inhibition in the contralesional hemisphere and high-frequency excitatory magnetic stimulation in the affected hemisphere can be performed. (3) In different brain functional network connection states, corresponding adjustment should be made to the treatment plan of rTMS to achieve optimal therapeutic effect and precise rehabilitation treatment.

Early structural connectivity within the sensorimotor network: Deviations related to prematurity and association to neurodevelopmental outcome.

Consisting of distributed and interconnected structures that interact through cortico-cortical connections and cortico-subcortical loops, the sensorimotor (SM) network undergoes rapid maturation during the perinatal period and is thus particularly vulnerable to preterm birth. However, the impact of prematurity on the development and integrity of the emerging SM connections and their relationship to later motor and global impairments are still poorly understood. In this study we aimed to explore to which extent the early microstructural maturation of SM white matter (WM) connections at term-equivalent age (TEA) is modulated by prematurity and related with neurodevelopmental outcome at 18 months corrected age. We analyzed 118 diffusion MRI datasets from the developing Human Connectome Project (dHCP) database: 59 preterm (PT) low-risk infants scanned near TEA and a control group of full-term (FT) neonates paired for age at MRI and sex. We delineated WM connections between the primary SM cortices (S1, M1 and paracentral region) and subcortical structures using probabilistic tractography, and evaluated their microstructure with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. To go beyond tract-specific univariate analyses, we computed a maturational distance related to prematurity based on the multi-parametric Mahalanobis distance of each PT infant relative to the FT group. Our results confirmed the presence of microstructural differences in SM tracts between PT and FT infants, with effects increasing with lower gestational age at birth. Maturational distance analyses highlighted that prematurity has a differential effect on SM tracts with higher distances and thus impact on (i) cortico-cortical than cortico-subcortical connections; (ii) projections involving S1 than M1 and paracentral region; and (iii) the most rostral cortico-subcortical tracts, involving the lenticular nucleus. These different alterations at TEA suggested that vulnerability follows a specific pattern coherent with the established WM caudo-rostral progression of maturation. Finally, we highlighted some relationships between NODDI-derived maturational distances of specific tracts and fine motor and cognitive outcomes at 18 months. As a whole, our results expand understanding of the significant impact of premature birth and early alterations on the emerging SM network even in low-risk infants, with possible relationship with neurodevelopmental outcomes. This encourages further exploration of these potential neuroimaging markers for prediction of neurodevelopmental disorders, with special interest for subtle neuromotor impairments frequently observed in preterm-born children.

Altered functional connectivity between primary motor cortex subregions and the whole brain in patients with incomplete cervical spinal cord injury.

To investigate the reorganizations of gray matter volume (GMV) in each subregion of primary motor cortex (M1) after incomplete cervical cord injury (ICCI) and to explore the differences in functional connectivity (FC) between the M1 subregions and the whole brain, and further to disclose the potential value of each M1 subregion in motor function rehabilitation of ICCI patients. Eighteen ICCI patients and eighteen age- and gender- matched healthy controls (HCs) were recruited in this study. The 3D high-resolution T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all subjects were obtained using a 3.0 Tesla MRI system. Based on the Human Brainnetome Atlas, the structural and functional changes of M1 subregions (including A4hf, A6cdl, A4ul, A4t, A4tl, A6cvl) in ICCI patients were analyzed by voxel-based morphometry (VBM) and seed-based FC, respectively. Compared with HCs, no structural changes in the M1 subregions of ICCI patients was detected. However, when compared with HCs, ICCI patients exhibited decreased FC in visual related areas (lingual gyrus, fusiform gyrus) and sensorimotor related areas (primary sensorimotor cortex) when the seeds were located in bilateral A4hf, A4ul, and decreased FC in visual related areas (lingual gyrus, fusiform gyrus) and cognitive related areas (temporal pole) when the seed was located in the left A4t. Moreover, when the seeds were located in the bilateral A6cdl, decreased FC in visual related areas (lingual gyrus, fusiform gyrus, calcarine gyrus) was also observed. Our findings demonstrated that each of the M1 regions had diverse FC reorganizations, which may provide a theoretical basis for the selection of precise stimulation targets, such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tCDS), meanwhile, our results may reveal the possible mechanism of visual feedback and cognitive training to promote motor rehabilitation.

Distinct local and brain-wide networks are activated by optogenetic stimulation of neurons specific to each layer of motor cortex

Primary motor cortex (M1) consists of a stack of interconnected but distinct layers (L1-L6) which affect motor control through large-scale networks. However, the brain-wide functional influence of each layer is poorly understood. We sought to expand our knowledge of these layers’ circuitry by combining Cre-driver mouse lines, optogenetics, fMRI, and electrophysiology. Neuronal activities initiated in Drd3 neurons (within L2/3) were mainly confined within M1, while stimulation of Scnn1a, Rbp4, and Ntsr1 neurons (within L4, L5, and L6, respectively) evoked distinct responses in M1 and motor-related subcortical regions, including striatum and motor thalamus. We also found that fMRI responses from targeted stimulations correlated with both local field potentials (LFPs) and spike changes. This study represents a step forward in our understanding of how different layers of primary motor cortex are embedded in brain-wide circuitry.

Evaluation of the posterior superior alveolar artery location and diameter with a newly defined stable plane

The aim of this study was to analyse the vertical location of the posterior superior alveolar artery (PSAA) using a reliable new reference plane regardless of tooth and alveolar bone, and to measure the diameter in each posterior tooth region, which is of relevance to lateral sinus floor elevation surgery. A total of 270 sinuses in 139 patients were examined in this study. The A-plane was defined by A-point and the bilateral jugal points on reconstructed three-dimensional images. The distance from the PSAA to the defined plane was measured in four regions: first premolar (P1), second premolar (P2), first molar (M1), and second molar (M2). The average distance of the PSAA above the plane in the P1, P2, M1, and M2 regions was determined to be 10.24mm, 7.35mm, 5.47mm, and 7.23mm, respectively. The PSAA was found to run above the plane in 97.4% of sinuses, below the plane in 1.1%, and on the plane in 1.5%. In conclusion, the new plane is useful for intraoperative location of the PSAA. According to the study findings, the area below the reference plane can be considered safe for lateral approach sinus surgery in terms of preserving the integrity of the PSAA.

Unequal Efficacy of Different Infarct Location in Predicting Futile Recanalization of Patients With Acute Ischemic Stroke.

ObjectivesEndovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) caused by large vessel occlusion, while futile recanalization is the main factor influencing the prognosis. The present study aimed to investigate the efficacy of different infarct sites in predicting futile recanalization of patients with AIS.MethodsData were obtained from two multicenter, prospective, randomized, and controlled trials, which were concurrently conducted in China. Cases achieving a successful recanalization and with complete data of preoperative Alberta Stroke Program Early CT score (ASPECTS) and 90-day follow-up were included. The ASPECTS subregions were used to mark different infarct locations in the two cerebral hemispheres. First, the distribution of each ASPECTS subregion in the left and right hemispheres and the whole brain was analyzed, respectively. Then, the regions associated with futile recanalization were initially assessed by a univariate model. Afterward, a multivariate logistic regression model was used to identify the efficacy of different infarct sites in predicting futile recanalization.ResultsA total of 336 patients were included in this study with a median age of 65 years (IQR: 51–74), of whom 210 (62.50%) patients were male, and 189 (56.25%) met the definition of futile recanalization. The correlation between each ASPECTS subregion and poor outcome was different when it was restricted to a specific cerebral hemisphere. Moreover, in the left hemisphere, the internal capsule region (OR: 1.42, 95%CI: 1.13–1.95, P = 0.03) and the M3 region (OR: 2.26, 95%CI: 1.36–3.52, P = 0.001), and in the right hemisphere, M6 region (OR: 2.24, 95%CI: 1.32–3.36, P = 0.001) showed significantly higher efficacy in predicting futile recanalization.ConclusionThe efficacy of different infarct locations in predicting futile recanalization is different. Different preoperative patterns of the high-efficiency regions in the infarction core or penumbra can guide the thrombectomy decision-making.

Iron quantitative analysis of motor combined with bulbar region in M1 cortex may improve diagnosis performance in ALS.

To explore whether the combined analysis of motor and bulbar region of M1 on susceptibility-weighted imaging (SWI) can be a valid biomarker for amyotrophic lateral sclerosis (ALS). Thirty-two non-demented ALS patients and 35 age- and gender-matched healthy controls (HC) were retrospectively recruited. SWI and 3D-T1-MPRAGE images were obtained from all individuals using a 3.0-T MRI scan. The bilateral posterior band of M1 was manually delineated by three neuroradiologists on phase images and subdivided into the motor and bulbar regions. We compared the phase values in two groups and performed a stratification analysis (ALSFRS-R score, duration, disease progression rate, and onset). Receiver operating characteristic (ROC) curves were also constructed. ALS group showed significantly increased phase values in M1 and the two subregions than the HC group, on the all and elderly level (p < 0.001, respectively). On all-age level comparison, negative correlations were found between phase values of M1 and clinical score and duration (p < 0.05, respectively). Similar associations were found in the motor region (p < 0.05, respectively). On both the total (p < 0.01) and elderly (p < 0.05) levels, there were positive relationships between disease progression rate and M1 phase values. In comparing ROC curves, the entire M1 showed the best diagnostic performance. Combining motor and bulbar analyses as an integral M1 region on SWI can improve ALS diagnosis performance, especially in the elderly. The phase value could be a valuable biomarker for ALS evaluation. • Integrated analysis of the motor and bulbar as an entire M1 region on SWI can improve the diagnosis performance in ALS. • Quantitative analysis of iron deposition by SWI measurement helps the clinical evaluation, especially for the elderly patients. • Phase value, when combined with the disease progression rate, could be a valuable biomarker for ALS.

Cerebro-cerebellar interactions in nonhuman primates examined by optogenetic functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) is a promising approach for the simultaneous and extensive scanning of whole-brain activities. Optogenetics is free from electrical and magnetic artifacts and is an ideal stimulation method for combined use with fMRI. However, the application of optogenetics in nonhuman primates (NHPs) remains limited. Recently, we developed an efficient optogenetic intracortical microstimulation method of the primary motor cortex (M1), which successfully induced forelimb movements in macaque monkeys. Here, we aimed to investigate how optogenetic M1 stimulation causes neural modulation in the local and remote brain regions in anesthetized monkeys using 7-tesla fMRI. We demonstrated that optogenetic stimulation of the M1 forelimb and hindlimb regions successfully evoked robust direct and remote fMRI activities. Prominent remote activities were detected in the anterior and posterior lobes in the contralateral cerebellum, which receive projections polysynaptically from the M1. We further demonstrated that the cerebro-cerebellar projections from these M1 regions were topographically organized, which is concordant with the somatotopic map in the cerebellar cortex previously reported in macaques and humans. The present study significantly enhances optogenetic fMRI in NHPs, resulting in profound understanding of the brain network, thereby accelerating the translation of findings from animal models to humans.

Structural Covariance of the Ipsilesional Primary Motor Cortex in Subcortical Stroke Patients with Motor Deficits.

The analysis of structural covariance has emerged as a powerful tool to explore the morphometric correlations among broadly distributed brain regions. However, little is known about the interactions between the damaged primary motor cortex (M1) and other brain regions in stroke patients with motor deficits. This study is aimed at investigating the structural covariance pattern of the ipsilesional M1 in chronic subcortical stroke patients with motor deficits. High-resolution T1-weighted brain images were acquired from 58 chronic subcortical stroke patients with motor deficits (29 with left-sided lesions and 29 with right-sided lesions) and 50 healthy controls. Structural covariance patterns were identified by a seed-based structural covariance method based on gray matter (GM) volume. Group comparisons between stroke patients (left-sided or right-sided groups) and healthy controls were determined by a permutation test. The association between alterations in the regional GM volume and motor recovery after stroke was investigated by a multivariate regression approach. Structural covariance analysis revealed an extensive increase in the structural interactions between the ipsilesional M1 and other brain regions in stroke patients, involving not only motor-related brain regions but also non-motor-related brain regions. We also identified a slightly different pattern of structural covariance between the left-sided stroke group and the right-sided stroke group, thus indicating a lesion-side effect of cortical reorganization after stroke. Moreover, alterations in the GM volume of structural covariance brain regions were significantly correlated to the motor function scores in stroke patients. These findings indicated that the structural covariance patterns of the ipsilesional M1 in chronic subcortical stroke patients were induced by motor-related plasticity. Our findings may help us to better understand the neurobiological mechanisms of motor impairment and recovery in patients with subcortical stroke from different perspectives.

Comparison of astrocytes and gap junction proteins in the white matter of genetic absence epileptic and control rats: an experimental study

ABSTRACT Objectives The role of white matter astrocytes in absence epilepsy is unknown. The present study aims to quantify astrocytic markers glial fibrillary acidic protein (GFAP), gap junction’s proteins connexin 30 (Cx30) and connexin 43 (Cx43) in the corpus callosum (CC) of genetic absence epileptic rats from Strasbourg (GAERS), Wistar albino glaxo rats from Rijswijk (WAG/Rij)and compare the results with control animals. Methods -The density of GFAP, Cx30 and Cx43 positive astrocytes in per unite area were quantified in the CC of GAERS, WAG/Rij and control animals using immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). The quantifications were made from three regions of CC; below the primary somatosensory (S1BF), below the motor (M1) and below the retrosplenial (RSG) cortices. Results oThe number GFAP, Cx30 and Cx43 immunopositive astrocytes showed heterogeneous distribution within the CC. The GFAP immunopositive astrocytes was significantly high in the S1BF region of the three strains. The immunopositive GFAP and Cx43 showed significant decrease in the S1BF and M1 regions in GAERS and WAG/Rij compared to control animals, however, an increase in the immunopositive Cx30 was observed in the same regions in both GAERS and WAG/Rij compared to control Wistar animals but the increase was significant for GAERS but not for WAG/Rij. The RT-qPCR analysis was corroborated by GFAP immunohistochemistry results. Conclusion The different expression pattern of the two Cx’s in the CC of the epileptic strains compared to control animals may indicate a compensatory response or maybe the cause of generalization of absence seizures.

Motor cortical patterns of upper motor neuron pathology in amyotrophic lateral sclerosis: A 3 T MRI study with iron-sensitive sequences

BackgroundPatterns of initiation and propagation of disease in Amyotrophic Lateral Sclerosis (ALS) are still partly unknown. Single or multiple foci of neurodegeneration followed by disease diffusion to contiguous or connected regions have been proposed as mechanisms underlying symptom occurrence. Here, we investigated cortical patterns of upper motor neuron (UMN) pathology in ALS using iron-sensitive MR imaging. MethodsSignal intensity and magnetic susceptibility of the primary motor cortex (M1), which are associated with clinical UMN burden and neuroinflammation, were assessed in 78 ALS patients using respectively T2*-weighted images and Quantitative Susceptibility Maps. The signal intensity of the whole M1 and each of its functional regions was rated as normal or reduced, and the magnetic susceptibility of each M1 region was measured. ResultsThe highest frequencies of T2* hypointensity were found in M1 regions associated with the body sites of symptom onset. Homologous M1 regions were both hypointense in 80–93 % of patients with cortical abnormalities, and magnetic susceptibility values measured in homologous M1 regions were strongly correlated with each other (ρ = 0.88; p < 0.0001). In some cases, the T2* hypointensity was detectable in two non-contiguous M1 regions but spared the cortex in between. ConclusionsM1 regions associated with the body site of onset are frequently affected at imaging. The simultaneous involvement of both homologous M1 regions is frequent, followed by that of adjacent regions; the affection of non-contiguous regions, instead, seems rare. This type of cortical involvement suggests the interhemispheric connections as one of the preferential paths for the UMN pathology diffusion in ALS.

Neurobehavioural Changes and not Structural Changes Occur in Rat Fed with Cassava Products (Fufu, Garri and Tapioca Diet)

The ability of cassava products (fufu, garri and tapioca) to produce behavioral and structural changes in the brain of adult rats was examined. Forty adult male rats (N=40) were used for this study and the experiment was divided into two phases (N=20 each).Rat were trained in a Reach-To-Grasp Task for 6 weeks and Quantitative assessments using a reaching movement scale and reach-to-grasp success rate were carried out to determine baseline values. After which administration of the various cassava products was done. The 1st phase had the rats trained to perform the reach to grasp experiment before been fed with various cassava diet. In this phase the animals performed significantly worse than the controls when determining the average success rate in a reach-to-grasp experiment (baseline=72.6%, fufu diet= 30%, garri diet =47%, tapioca diet =59%). The 2nd phase had the rats trained simultaneously as they were being fed withvarious cassava diet. In this phase the animals also performed significantly worse than the controls when determining the average success rate in a reach-to-grasp experiment (fufu diet= 37.5%, garri diet =46.5%, tapioca diet =56.5%). The various movement of the rat was assessed using Tracker software (Video Analysis and Modeling tool, version 5.1.2) and the movement pattens were determined. The animals fed with Fufu shows the worst movement pattern indicating aiming impairment which may be as a result of structural changes in the m1 region of the cerebral cortex. The data obtained were analysed using ANOVA and there was significant difference (p &lt; 0.05) in the movement pattern. Histological observation showed no neuropathological changes in the motor cortex. The rats fed with cassava diets shows no observable changes in the structures and sizes of the neurons as compared with the control. Cassava products (Fufu, Garri and Tapioca) have been demonstrated to cause neurobehavioural and mild structural changes in the M1 region of the cerebral cortex.

Asymmetric directed functional connectivity within the frontoparietal motor network during motor imagery and execution

Both imagery and execution of motor control consist of interactions within a neuronal network, including frontal motor-related and posterior parietal regions. To reveal neural representation in the frontoparietal motor network, two approaches have been proposed thus far: one is decoding of actions/modes related to motor control from the spatial pattern of brain activity; and the other is estimating directed functional connectivity (a directed association between two brain regions within motor areas). However, directed connectivity among multiple regions of the frontoparietal motor network during motor imagery (MI) or motor execution (ME) has not been investigated. Here, we attempted to characterize the directed functional connectivity representing the MI and ME conditions. We developed a delayed sequential movement and imagery task to evoke brain activity associated with ME and MI, which can be recorded by functional magnetic resonance imaging. We applied a causal discovery approach, a linear non-Gaussian acyclic causal model, to identify directed functional connectivity among the frontoparietal motor-related brain regions for each condition. We demonstrated higher directed functional connectivity from the contralateral dorsal premotor cortex (dPMC) to the primary motor cortex (M1) in ME than in MI. We further identified significant direct effects of the dPMC and ventral premotor cortex (vPMC) to the parietal regions. In particular, connectivity from the dPMC to the superior parietal lobule (SPL) in the same hemisphere showed significant positive effects across all conditions, while interlateral connectivities from the vPMC to the SPL showed significantly negative effects across all conditions. Finally, we found positive effects from A1 to M1, that is, the audio-motor pathway, in the same hemisphere. These results indicate that the sources of motor command originating in the d/vPMC influenced the M1 and parietal regions for achieving ME and MI. Additionally, sequential sounds may functionally facilitate temporal motor processes.

Modulatory effect of continuous theta burst stimulation in patients with essential tremor

IntroductionWe aimed to study the cortical and intracortical functions in patients of ET using transcranial magnetic stimulation (TMS) and to evaluate the effect of continuous theta burst stimulation (cTBS) on the tremor characteristics. MethodsTen ET and 20 healthy controls were included in the study. All the participants were evaluated with TMS with recording of resting motor threshold (RMT), central motor conduction time, contralateral silent period (cSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Subsequently only ET patients underwent cTBS of the motor cortex (M1) followed by repeat TMS. ResultsThe mean age of the patients (46.5 ± 17.2 years) was comparable to healthy controls (55.4 ± 9.2 years; p = 0.16). There was a non-significant increase in RMT in ET patients (44 ± 12.5%) when compared to healthy controls (40.9 ± 6.9%; p = 0.48). There was a significant reduction of cSP in the ET group (102.03 ± 15.26 msec) compared to healthy controls (116.1 ± 15.2, p = 0.03). In addition, a significant reduction in ICF was observed in ET patients (0.9 ± 0.7) compared to healthy controls (1.8 ± 0.8, p = 0.01). Following cTBS there was a significant reduction in the tremor scores [FTMRS (Pre-cTBS: 29.3 ± 18.7, Post-cTBS: 25.3 ± 16.8; p < 0.001) and TETRAS (pre-cTBS: 34.4 ± 16.2, post-cTBS: 29.8 ± 12.1; p = 0.01)] and improvement (increase) of the duration of cSP (pre-cTBS: 102.03 ± 15.3 msec., post-cTBS: 119.4 ± 12.03 msec; p = 0.05). ConclusionsPatients with ET have GABAergic and glutaminergic dysfunction as demonstrated by reduced cSP and ICF. However, only the cSP improved following cTBS of M1 region, with a corresponding improvement of tremor severity suggesting the effect of cTBS on the cerebello-thalamo-cortical network.

TMS based lower extremity multi-muscle motor mapping in persons post-stroke with impaired muscle coordination

Abstract Co-excitation of normally independent muscle groups or modules can explain impaired motor coordination during walking. Mass flexion-extension co-excitation patterns (i.e., only two or three modules instead of the usually observed four modules) are often seen as a consequence of stroke. The corticospinal (CST) and corticoreticular (CRP) networks are major contributors to the production of modules during walking. A structural MRI-based analysis from our lab found that both CST and CRP are involved in locomotor recovery post-stroke and greater involvement of both ipsi- and contralesional CRP is associated with mass flexion-extension synergy leading to a two module pattern and poor walking ability. In the current study, we will further investigate the relationship between a two module pattern and ipsi- and contralesional cortical reorganization with TMS derived motor mapping during standing. Utilizing neuronavigation a 6x8 grid with 1.25 cm between grid points will be centered over individual participants’ T1 image. The motor threshold of the paretic tibialis anterior muscle will be determined during standing (functionally-relevant to walking) with a double-cone coil positioned over the vertex. Ten stimulations at an intensity of 140% of motor threshold will be delivered to each grid point over both hemispheres. Visual feedback will be provided to ensure equal weight distribution between the legs during standing. The average motor evoked potential amplitude and response latency from eight muscles of each leg will be used for motor mapping. We hypothesize that the individuals who have severely damaged CST and two module patterns of walking will have reorganization of leg motor representation in contralesional M1 and/or cortical regions associated with CRP (i.e., supplementary motor area and pre-motor cortex of the ipsi-and-contralesional hemispheres). This ongoing study will provide essential knowledge of the cortical contributions to modules and eventually be applicable to designing patient-specific neuromodulation rehabilitation techniques. Keywords: TMS, motor coordination, gait, Structural MRI

The M1 and pre-M1 segments contribute differently to ion selectivity in ASICs and ENaCs.

The ability to discriminate between different ionic species, termed ion selectivity, is a key feature of ion channels and forms the basis for their physiological function. Members of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily of trimeric ion channels are typically sodium selective, but to a surprisingly variable degree. While acid-sensing ion channels (ASICs) are weakly sodium selective (sodium:potassium ratio ∼10:1), ENaCs show a remarkably high preference for sodium over potassium (>500:1). This discrepancy may be expected to originate from differences in the pore-lining second transmembrane segment (M2). However, these show a relatively high degree of sequence conservation between ASICs and ENaCs, and previous functional and structural studies could not unequivocally establish that differences in M2 alone can account for the disparate degrees of ion selectivity. By contrast, surprisingly little is known about the contributions of the first transmembrane segment (M1) and the preceding pre-M1 region. In this study, we used conventional and noncanonical amino acid-based mutagenesis in combination with a variety of electrophysiological approaches to show that the pre-M1 and M1 regions of mASIC1a channels are major determinants of ion selectivity. Mutational investigations of the corresponding regions in hENaC show that these regions contribute less to ion selectivity, despite affecting ion conductance. In conclusion, our work suggests that the remarkably different degrees of sodium selectivity in ASICs and ENaCs are achieved through different mechanisms. These results further highlight how M1 and pre-M1 are likely to differentially affect pore structure in these related channels.

Effect of P21 buffer layer on interfacial bonding characteristics of high‑carbon tool steel hardfaced through directed energy deposition

The elevated hardness of high‑carbon tool steel (M2) powder makes it an effective material for hardfacing components requiring strong wear resistance. However, if the brittle M2 powder is deposited on a ductile substrate, significant stress occurs during cooling, leading to defects, such as cracks at the interface between the substrate and deposited regions. Therefore, in this study, ductile P21 powder was deposited as a buffer layer between the substrate and the deposited M2 layer to prevent interface defects. To confirm whether this P21 buffer layer effectively prevents interfacial defects, bending, impact, and tensile tests were performed. No interfacial defects were observed in the cross-section of the deposition specimen when a P21 buffer layer was applied. The average hardness of the surface deposited M2 region was 733 HV, similar to that of the carburized substrate. As-built (M2) specimen showed 94% lower in weight reduction than the carburized material after the wear test. The specimen without a buffer layer revealed cracks propagating along the interface between the deposited region and substrate, with the lowest impact energy absorption of 25 J. However, the energy absorption of the specimen with a P21 buffer layer was 60% higher than that without a buffer layer. The tensile test results show 7% increase in tensile strength with the buffer layer and 244% increase in elongation. This study demonstrated that high hardness and wear resistance could be achieved through M2 deposition and confirmed the improved strength and toughness with a P21 buffer layer.

Abstract NG12: From cholesterol regulation to tumor suppression: Pcsk9 as a novel target for cancer immunotherapy

Abstract NG12: From cholesterol regulation to tumor suppression: Pcsk9 as a novel target for cancer immunotherapy

Differential Contribution of ASPECTS Regions to Clinical Outcome after Thrombectomy for Acute Ischemic Stroke.

Ischemic stroke is the leading cause of long-term disability in adults, but our ability to prognosticate from baseline imaging data is limited. The ASPECTS measures ischemic change in the middle cerebral artery territory on noncontrast CT based on 10 anatomic regions. Here, we investigated whether infarction in particular regions was associated with worse long-term outcome. We identified consecutive patients receiving mechanical thrombectomy for ICA/MCA occlusion at 2 comprehensive stroke centers. Pretreatment ASPECTS was assessed by 2 blinded reviewers. Clinical data including demographics, baseline NIHSS score, and 90-day mRS were collected. The relationship between individual ASPECTS regions and the mRS score (0-2 versus 3-6) was assessed using multivariable logistic regression. Three hundred fifty-three patients were included (mean age, 70 years; 46% men), of whom 214 had poor outcome (mRS = 3-6). Caudate (OR = 3.26; 95% CI, 1.33-8.82), M4 region (OR = 2.94; 95% CI, 1.09-9.46), and insula (OR = 1.75; 95% CI, 1.08-2.85) infarcts were associated with significantly greater odds of poor outcome, whereas M1 region infarction reduced the odds of poor outcome (OR = 0.38; 95% CI, 0.14-0.99). This finding remained unchanged when restricted to only patients with good recanalization. No significant associations were found by laterality. Similarly, no region was predictive of neurologic improvement during the first 24 hours or of symptomatic intracerebral hemorrhage. Our results indicate that ASPECTS regions are not equal in their contribution to functional outcome. This finding suggests that patient selection based on total ASPECTS alone might be insufficient, and infarct topography should be considered when deciding eligibility for thrombectomy.

ASPECTS-Region-Dependent Functional Outcomes after Endovascular Therapy in Patients with Cardioembolic Stroke

ObjectivesCardioembolic stroke has a poor prognosis. We evaluated the region-dependent efficacy of endovascular therapy (EVT) based on diffusion-weighted imaging-Alberta Stroke Program Early CT Score (DWI-ASPECTS). MethodsThis post-hoc analysis of the RELAXED study, which investigated the optimal timing of rivaroxaban to prevent nonvalvular atrial fibrillation (NVAF) recurrence in patients with acute ischemic stroke (AIS), included NVAF patients admitted with AIS or transient ischemic attack in the middle cerebral artery (MCA), with internal carotid artery (ICA), M1, or M2-MCA occlusion. Relationships between DWI-ASPECTS region and functional outcome (modified Rankin Scale [mRS]), mortality, recurrence, and hemorrhagic stroke were compared between patients with and without EVT, and adjusted odds ratios for age, pre-stroke mRS, National Institutes of Health Stroke Scale (NIHSS), ICA occlusion, infarct size, recombinant tissue plasminogen activator (rt-PA) use, and onset-to-hospitalization time were estimated. ResultsEVT patients had significantly lower hemoglobin levels, higher median NIHSS scores, more lentiform nucleus infarcts, ICA or M1-MCA occlusions, treatment with rt-PA, and fewer M3, M5, or M6 infarcts and M2-MCA occlusions than no-EVT patients. EVT patients had shorter onset-to-hospitalization times and more frequent favorable functional outcomes (p=0.007). Mortality, recurrent ischemic stroke, and hemorrhagic infarction were similar in both groups. EVT was associated with significantly better functional outcomes among patients with insular ribbon (p=0.043) and M3 (p=0.0008) infarcts. M3 patients had significantly fewer rt-PA and EVT, and longer onset-to-hospitalization times. ConclusionsAn occlusion in the insular ribbon or M3 region was associated with favorable functional outcomes in patients treated with EVT after cardioembolic stroke.