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Multiple sensorimotor loops converge in the motor cortex to create an adaptable system capable of context-specific sensorimotor control. Afferent inhibition provides a non-invasive tool to investigate the substrates by which procedural and cognitive control processes interact to shape motor corticospinal projections. Varying the transcranial magnetic stimulation properties during afferent inhibition can probe specific sensorimotor circuits that contribute to short- and long-latency periods of inhibition in response to the peripheral stimulation. The current study used short- (SAI) and long-latency (LAI) afferent inhibition to probe the influence of verbal and spatial working memory load on the specific sensorimotor circuits recruited by posterior-anterior (PA) and anterior-posterior (AP) TMS-induced current. Participants completed two sessions where SAI and LAI were assessed during the short-term maintenance of two- or six-item sets of letters (verbal) or stimulus locations (spatial). The only difference between the sessions was the direction of the induced current. PA SAI decreased as the verbal working memory load increased. In contrast, AP SAI was not modulated by verbal working memory load. Visuospatial working memory load did not affect PA or AP SAI. Neither PA LAI nor AP LAI were sensitive to verbal or spatial working memory load. The dissociation of short-latency PA and AP sensorimotor circuits and short- and long-latency PA sensorimotor circuits with increasing verbal working memory load support multiple convergent sensorimotor loops that provide distinct functional information to facilitate context-specific supraspinal control. [ABSTRACT FROM AUTHOR]

Abnormalities of postural sway have been extensively reported in traumatic brain injury (TBI). However, the underlying neural correlates of balance disturbances in TBI remain to be elucidated. Studies in children with TBI have reported associations between the Sensory Organization Test (SOT) and measures of white matter (WM) integrity with diffusion tensor imaging (DTI) in brain areas responsible for multisensory integration. This study seeks to replicate those associations in adults as well as explore relationships between DTI and the Limits of Stability (LOS) Test. Fifty-six participants (43±17 years old) with a history of TBI were tested 30 days to 5 years post-TBI. This study confirmed results in children for associations between the SOT and the medial lemniscus as well as middle cerebellar peduncle, and revealed additional associations with the posterior thalamic radiation. Additionally, this study found significant correlations between abnormal LOS scores and impaired WM integrity in the cingulum, corpus callosum, corticopontine and corticospinal tracts, fronto-occipital fasciculi, longitudinal fasciculi, medial lemniscus, optic tracts and thalamic radiations. Our findings indicate the involvement of a broad range of WM tracts in the control of posture, and demonstrate the impact of TBI on balance via disruptions to WM integrity. [ABSTRACT FROM AUTHOR]

Relapsing-remitting Multiple Sclerosis is the most common demyelinating neurodegenerative disease and is characterized by periods of relapses and generation of various motor symptoms. These symptoms are associated with the corticospinal tract integrity, which is quantified by means of corticospinal plasticity which can be probed via transcranial magnetic stimulation and assessed with corticospinal excitability measures. Several factors, such as exercise and interlimb coordination, can influence corticospinal plasticity. Previous work in healthy and in chronic stroke survivors showed that the greatest improvement in corticospinal plasticity occurred during in-phase bilateral exercises of the upper limbs. During in-phase bilateral movement, both upper limbs are moving simultaneously, activating the same muscle groups and triggering the same brain region respectively. Altered corticospinal plasticity due to bilateral cortical lesions is common in MS, yet, the impact of these type of exercises in this cohort is unclear. The aim of this concurrent multiple baseline design study is to investigate the effects of in-phase bilateral exercises on corticospinal plasticity and on clinical measures using transcranial magnetic stimulation and standardized clinical assessment in five people with relapsing-remitting MS. The intervention protocol will last for 12 consecutive weeks (30–60 minutes /session x 3 sessions/week) and include in-phase bilateral movements of the upper limbs, adapted to different sports activities and to functional training. To define functional relation between the intervention and the results on corticospinal plasticity (central motor conduction time, resting motor threshold, motor evoked potential amplitude and latency) and on clinical measures (balance, gait, bilateral hand dexterity and strength, cognitive function), we will perform a visual analysis and if there is a potential sizeable effect, we will perform statistical analysis. A possible effect from our study, will introduce a proof-of-concept for this type of exercise that will be effective during disease progression. Trial registration: ClinicalTrials.gov NCT05367947. [ABSTRACT FROM AUTHOR]

Objective: This study investigated how peripheral axonal excitability changes in ischemic stroke patients with hemiparesis or hemiplegia, reflecting the plasticity of motor axons due to corticospinal tract alterations along the poststroke stage. Methods: Each subject received a clinical evaluation, nerve conduction study, and nerve excitability test. Nerve excitability tests were performed on motor median nerves in paretic and non-paretic limbs in the acute stage of stroke. Control nerve excitability test data were obtained from age-matched control subjects. Some patients underwent excitability examinations several times in subacute or chronic stages. Results: A total of thirty patients with acute ischemic stroke were enrolled. Eight patients were excluded due to severe entrapment neuropathy in the median nerve. The threshold current for 50% compound muscle action potential (CMAP) was higher in paretic limbs than in control subjects. Furthermore, in the cohort with severe patients (muscle power ≤ 3/5 in affected hands), increased threshold current for 50% CMAP and reduced subexcitability were noted in affected limbs than in unaffected limbs. In addition, in the subsequent study of those severe patients, threshold electrotonus increased in the hyperpolarization direction: TEh (100–109 ms), and the minimum I/V slope decreased. The above findings suggest the less excitable and less accommodation in lower motor axons in the paretic limb caused by ischemic stroke. Conclusion: Upper motor neuron injury after stroke can alter nerve excitability in lower motor neurons, and the changes are more obvious in severely paretic limbs. The accommodative changes of axons progress from the subacute to the chronic stage after stroke. Further investigation is necessary to explore the downstream effects of an upper motor neuron insult in the peripheral nerve system. [ABSTRACT FROM AUTHOR]

Paired associative corticospinal-motoneuronal stimulation (PCMS) induces plasticity at synapses between corticospinal tracts (CSTs) and spinal motoneurons (SMs). We investigated the effects of peripheral nerve electrical stimulation (PNS) intensity on PCMS-induced plasticity. PCMS consisted of 180 paired stimuli of transcranial magnetic stimulation (TMS) over the left primary motor cortex with PNS on the right ulnar nerve at the wrist. We compared effects induced by different PNS intensities: supramaximal, twice and three times sensory threshold intensities. For evaluating efficacy of the synapse between CSTs and SMs, single-pulse TMS was delivered at cervicomedullary junction level, and cervicomedullary motor-evoked potentials (CMEPs) were recorded from the right first-dorsal interosseous muscle before and after PCMS. PCMS with the supramaximal PNS intensity increased CMEP amplitude. The facilitatory effect of PCMS with the supramaximal PNS was larger than those of PCMS with weaker PNS intensities. Sham TMS with the supramaximal PNS showed no CMEP changes after the intervention. PNS intensity of PCMS influences the magnitude of synaptic plasticity induction between the CSTs and SMs at the spinal level, and the supramaximal intensity is the best for induction of long-term potentiation-like effects. The PNS intensity may influence the number of activated SMs by axonal backpropagating pulses with PNS which must overlap with descending volleys induced by TMS. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (MI) is expected to provide a therapeutic impact on spinal cord injury (SCI). On the other hand, treatment with antibody against repulsive guidance molecule-a (RGMa) has been shown to ameliorate motor deficits after SCI in rodents and primates. Facilitating activity of the corticospinal tract (CST) by rTMS following rewiring of CST fibers by anti-RGMa antibody treatment may exert an enhanced effect on motor recovery in a primate model of SCI. To address this issue, we examined whether such a combined therapeutic strategy could contribute to accelerating functional restoration from SCI. In our SCI model, unilateral lesions were made between the C6 and the C7 level. Two macaque monkeys were used for each of the combined therapy and antibody treatment alone, while one monkey was for rTMS alone. The antibody treatment was continuously carried out for four weeks immediately after SCI, and rTMS trials applying a thermoplastic mask and a laser distance meter lasted ten weeks. Behavioral assessment was performed over 14 weeks after SCI to investigate the extent to which motor functions were restored with the antibody treatment and/or rTMS. While rTMS without the preceding antibody treatment produced no discernible sign for functional recovery, a combination of the antibody and rTMS exhibited a greater effect, especially at an early stage of rTMS trials, on restoration of dexterous hand movements. The present results indicate that rTMS combined with anti-RGMa antibody treatment may exert a synergistic effect on motor recovery from SCI. [ABSTRACT FROM AUTHOR]

Introduction: Core symptomatology in idiopathic normal pressure hydrocephalus (iNPH) points at dysfunction in the mesencephalon and pons indicating pathological changes in these regions, but only a few studies have addressed the issue. The aim of this study was to investigate diffusion (ADC) and perfusion patterns pre- and postoperatively in these areas in iNPH. Methods: Twenty iNPH patients and 15 healthy controls were included. Patients underwent a clinical examination and brain MRI pre- and 3–6 months postoperatively. The MRI-scan included diffusion and dynamic susceptibility contrast perfusion weighted sequences. Regions of interest in the mesencephalon and pons were drawn on a FLAIR sequence and co-registered to ADC maps and perfusion data. Results: There were no significant differences in pre or postoperative ADC compared to the control group, however postoperative ADC increased by 10% (p = 0.026) in the mesencephalon and 6% (p = 0.016) in the pons in all patients and also in the subgroup of shunt responders by 11% (p = 0.021) and 4% (p = 0.020), respectively. Preoperative relative cerebral blood flow (rCBF) was similar in iNPH patients and controls. Postoperatively, rCBF increased in shunt responders by 6% (p = 0.02) in the mesencephalon and 11% (p = 0.004) in the pons. This increase correlated with the degree of clinical improvement (rs = 0.80, p = 0.031 and rs = 0.66, p = 0.021, respectively). Conclusion: The postoperative increase in ADC and the correlation between postoperative increase in rCBF and clinical improvement in the mesencephalon and pons shown in this study point at an involvement of these areas in the core pathophysiology and its reversibility in iNPH. [ABSTRACT FROM AUTHOR]

Objectives: It is commonly accepted that motor imagery (MI), i.e. the mental simulation of a movement, leads to an increased size of cortical motor evoked potentials (MEPs), although the magnitude of this effect differs between studies. Its impact on the spinal level is even more variable in the literature. Such discrepancies may be explained by many different experimental approaches. Therefore, the question of the optimal stimulation parameters to assess both spinal and corticospinal excitabilities remains open. Methods: H-reflexes and MEPs of the triceps surae were evoked in 11 healthy subjects during MI, weak voluntary contraction (CON) and rest (REST). In each condition, the full recruitment curve from the response threshold to maximal potential was investigated. Results: At stimulation intensities close to the maximal response, MEP amplitude was increased by CON compared to REST on the triceps surae. No effect of the different conditions was found on the H-reflex recruitment curve, except a small variation beyond maximal H-reflex in the soleus muscle. Conclusion: Based on our results, we recommend to assess corticospinal excitability between 70% and 100% of maximal MEP intensity instead of the classical use of a percentage of the motor threshold and to elicit H-reflexes on the ascending part of the recruitment curve. [ABSTRACT FROM AUTHOR]

The vestibular system is essential to produce adequate postural responses enabling voluntary movement. However, how the vestibular system influences corticospinal output during postural tasks is still unknown. Here, we examined the modulation exerted by the vestibular system on corticospinal output during standing. Healthy subjects (n = 25) maintained quiet standing, head facing forward with eyes closed. Galvanic vestibular stimulation (GVS) was applied bipolarly and binaurally at different delays prior to transcranial magnetic stimulation (TMS) which triggered motor evoked potentials (MEPs). With the cathode right/anode left configuration, MEPs in right Soleus (SOL) muscle were significantly suppressed when GVS was applied at ISI = 40 and 130ms before TMS. With the anode right/cathode left configuration, no significant changes were observed. Changes in the MEP amplitude were then compared to changes in the ongoing EMG when GVS was applied alone. Only the decrease in MEP amplitude at ISI = 40ms occurred without change in the ongoing EMG, suggesting that modulation occurred at a premotoneuronal level. We further investigated whether vestibular modulation could occur at the motor cortex level by assessing changes in the direct corticospinal pathways using the short-latency facilitation of the SOL Hoffmann reflex (H-reflex) by TMS. None of the observed modulation occurred at the level of motor cortex. Finally, using the long-latency facilitation of the SOL H-reflex, we were able to confirm that the suppression of MEP at ISI = 40ms occurred at a premotoneuronal level. The data indicate that vestibular signals modulate corticospinal output to SOL at both premotoneuronal and motoneuronal levels during standing. [ABSTRACT FROM AUTHOR]

Paired associative stimulation (PAS) combines transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) to induce plastic changes in the corticospinal tract. PAS employing single 0.2-Hz TMS pulses synchronized with the first pulse of 50–100 Hz PNS trains potentiates motor-evoked potentials (MEPs) in a stable manner in healthy participants and enhances voluntary motor output in spinal cord injury (SCI) patients. We further investigated the impact of settings of this PAS variant on MEP potentiation in healthy subjects. In experiment 1, we compared 0.2-Hz vs 0.4-Hz PAS. In experiment 2, PNS frequencies of 100 Hz, 200 Hz, and 400 Hz were compared. In experiment 3, we added a second TMS pulse. When compared with 0.4-Hz PAS, 0.2-Hz PAS was significantly more effective after 30 minutes (p = 0.05) and 60 minutes (p = 0.014). MEP potentiation by PAS with 100-Hz and 200-Hz PNS did not differ. PAS with 400-Hz PNS was less effective than 100-Hz (p = 0.023) and 200-Hz (p = 0.013) PNS. Adding an extra TMS pulse rendered PAS strongly inhibitory. These negative findings demonstrate that the 0.2-Hz PAS with 100-Hz PNS previously used in clinical studies is optimal and the modifications employed here do not enhance its efficacy. [ABSTRACT FROM AUTHOR]

In contrast to commonly used approaches to improve data quality in diffusion weighted imaging, position-orientation adaptive smoothing (POAS) provides an edge-preserving post-processing approach. This study aims to investigate its potential and effects on image quality, diffusion metrics, and fiber tractography of the corticospinal tract in relation to non-post-processed and averaged data. 22 healthy volunteers were included in this study. For each volunteer five clinically applicable diffusion weighted imaging data sets were acquired and post-processed by standard averaging and POAS. POAS post-processing led to significantly higher signal-to-noise-ratios (p < 0.001), lower fractional anisotropy across the whole brain (p < 0.05) and reduced intra-subject variability of diffusion weighted imaging signal intensity and fractional anisotropy (p < 0.001, p = 0.006). Fiber tractography of the corticospinal tract resulted in significantly (p = 0.027, p = 0.014) larger tract volumes while fiber density was the lowest. Similarity across tractography results was highest for POAS post-processed data (p < 0.001). POAS post-processing enhances image quality, decreases the intra-subject variability of signal intensity and fractional anisotropy, increases fiber tract volume of the corticospinal tract, and leads to higher reproducibility of tractography results. Thus, POAS post-processing supports a reliable and more accurate fiber tractography of the corticospinal tract, being mandatory for the clinical use. [ABSTRACT FROM AUTHOR]

Background and purpose: There is limited standardization of acquisition and processing methods in diffusion tractography for pre-surgical planning, leading to a range of approaches. In this study, a number of representative acquisition variants and post processing methods are considered, to assess their importance when implementing a clinical tractography program. Methods: Diffusion MRI was undertaken in ten healthy volunteers, using protocols typical of clinical and research scanning: a 32-direction diffusion acquisition with and without peripheral gating, and a non-gated 64 diffusion direction acquisition. All datasets were post-processed using diffusion tensor reconstruction with streamline tractography, and with constrained spherical deconvolution (CSD) with both streamline and probabilistic tractography, to delineate the cortico-spinal tract (CST) and optic radiation (OR). The accuracy of tractography results was assessed against a histological atlas using a novel probabilistic Dice overlap technique, together with direct comparison to tract volumes and distance of Meyer's loop to temporal pole (ML-TP) from dissections studies. Three clinical case studies of patients with space occupying lesions were also investigated. Results: Tracts produced by CSD with probabilistic tractography provided the greatest overlap with the histological atlas (overlap scores of 44% and 52% for the CST and OR, respectively) and best matched tract volume and ML-TP distance from dissection studies. The acquisition protocols investigated had limited impact on the accuracy of the tractography. In all patients, the CSD based probabilistic tractography created tracts with greatest anatomical plausibility, although in one case anatomically plausible pathways could not be reconstructed without reducing the probabilistic threshold, leading to an increase in false positive tracts. Conclusions: Advanced post processing techniques such as CSD with probabilistic tractography are vital for pre-surgical planning. However, overall accuracy relative to dissection studies remains limited. [ABSTRACT FROM AUTHOR]

Even though the acute effects of pre-exercise static stretching and dynamic muscle activity on muscular and functional performance have been largely investigated, their effects on the corticospinal pathway are still unclear. For that reason, this study examined the acute effects of 5×20 s of static stretching, dynamic muscle activity and a control condition on spinal excitability, corticospinal excitability and plantar flexor neuromuscular properties. Fifteen volunteers were randomly tested on separate days. Transcranial magnetic stimulation was applied to investigate corticospinal excitability by recording the amplitude of the motor-evoked potential (MEP) and the duration of the cortical silent period (cSP). Peripheral nerve stimulation was applied to investigate (i) spinal excitability using the Hoffmann reflex (Hmax), and (ii) neuromuscular properties using the amplitude of the maximal M-wave (Mmax) and corresponding peak twitch torque. These measurements were performed with a background 30% of maximal voluntary isometric contraction. Finally, the maximal voluntary isometric contraction torque and the corresponding electromyography (EMG) from soleus, gastrocnemius medialis and gastrocnemius lateralis were recorded. These parameters were measured immediately before and 10 s after each conditioning activity of plantar flexors. Corticospinal excitability (MEP/Mmax) was significantly enhanced after static stretching in soleus (P = 0.001; ES = 0.54) and gastrocnemius lateralis (P<0.001; ES = 0.64), and after dynamic muscle activity in gastrocnemius lateralis (P = 0.003; ES = 0.53) only. On the other hand, spinal excitability (Hmax/Mmax), cSP duration, muscle activation (EMG/Mmax) as well as maximal voluntary and evoked torque remained unaltered after all pre-exercise interventions. These findings indicate the presence of facilitation of the corticospinal pathway without change in muscle function after both static stretching (particularly) and dynamic muscle activity. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) has been widely utilized to noninvasively explore the motor system during the observation of human movement. However, few studies have characterized motor cortex activity during periodic gait observation. Thus, this study examined the effects of an observer's visual experience and/or intention to imitate on corticospinal excitability during the observation of another's gait. Twenty-six healthy volunteers were included in this study and allocated to two different groups. Participants in the visual experience group had formal experience with gait observation (physical therapist training), while those in the control group did not. Motor-evoked potentials induced by TMS in the tibialis anterior and soleus muscles were measured as surrogates of corticospinal excitability. Participants were seated and, while resting, they observed a demonstrator's gait or observed it with the intention to subsequently reproduce it. Compared with the resting state, cyclic gait observation led to significant corticospinal facilitation in the tibialis anterior and soleus muscles. However, this pattern of corticospinal facilitation in the measured muscles was not coupled to the pattern of crural muscle activity during actual gait and was independent of the step cycle. This motor cortex facilitation effect during gait observation was enhanced by the observer's visual experience in a manner that was not step cycle-dependent, while the observer's intent to imitate did not affect corticospinal excitatory input to either muscle. In addition, visual experience did not modulate corticospinal excitability in gait-related crural muscles. Our findings indicate that motor cortex activity during gait observation is not in line with the timing of muscle activity during gait execution and is modulated by an individual's gait observation experience. These results suggest that visual experience acquired from repetitive gait observation may facilitate the motor system's control on bipedal walking, but may not promote the learning of muscle activity patterns. [ABSTRACT FROM AUTHOR]

Background and objectives: Respiratory muscles dysfunction has been reported in COPD. Transcranial magnetic stimulation (TMS) has been used for assessing the respiratory corticospinal pathways particularly of diaphragm. We aimed to study the cortico-diaphragmatic motor system changes in COPD using TMS and to correlate the findings with the pulmonary function. Methods: A case control study recruited 30 stable COPD from the out-patient respiratory clinic of Main Alexandria University hospital- Egypt and 17 healthy control subjects who were subjected to spirometry. Cortical conduction of the diaphragm was performed by TMS to all participants followed by cervical magnetic stimulation of the phrenic nerve roots. Diaphragmatic resting motor threshold (DRMT), cortical motor evoked potential latency (CMEPL), CMEP amplitude (CMEPA), peripheral motor evoked potential latency (PMEPL), PMEP amplitude (PMEPA) and central motor conduction time (CMCT) were measured. Results: 66.7% of COPD patients had severe and very severe COPD with median age of 59 (55–63) years. There was statistically significant bilateral decrease in DRMT, CMEPA and PMEPA in COPD group versus healthy subjects and significant increase in CMEPL and PMEPL (p <0.01). Left CMCT was significantly prolonged in COPD group versus healthy subjects (p <0.0001) but not right CMCT. Further, there was significant increase in CMEPL and CMCT of left versus right diaphragm in COPD group (p = 0.003 and 0.001 respectively) that inversely correlated with FEV1% and FVC% predicted. Right and left DRMT were insignificantly different in COPD group (p >0.05) but positively correlated with FEV1/FVC, FEV1% and FVC% predicted. Conclusion: Central cortico-diaphragmatic motor system is affected in COPD patients with heterogeneity of both sides that is correlated with pulmonary function. Significance: Coticospinal pathway affection could be a factor for development of diaphragmatic dysfunction in COPD patients accordingly its evaluation could help in personalization of COPD management especially pulmonary rehabilitation programs. [ABSTRACT FROM AUTHOR]

Gliomas account for 26.5% of all primary central nervous system tumors. Recent studies have used diffusion tensor imaging (DTI) to extract white matter fibers and the diffusion coefficients derived from MR processing to provide useful, non-invasive insights into the extent of tumor invasion, axonal integrity, and gross differentiation of glioma from metastasis. Here, we extend this work by examining whether a tract-based analysis can improve non-invasive localization of tumor impact on white matter integrity. This study retrospectively analyzed preoperative magnetic resonance sequences highlighting contrast enhancement and DTI scans of 13 subjects that were biopsy-confirmed to have either high or low-grade glioma. We reconstructed the corticospinal tract and superior longitudinal fasciculus by applying atlas-based regions of interest to fibers derived from whole-brain deterministic streamline tractography. Within-subject comparison of hemispheric diffusion coefficients (e.g., fractional anisotropy and mean diffusivity) indicated higher levels of white matter degradation in the ipsilesional hemisphere. Novel application of along-tract analyses revealed that tracts traversing the tumor region showed significant white matter degradation compared to the contralesional hemisphere and ipsilesional tracts displaced by the tumor. [ABSTRACT FROM AUTHOR]

Although observing other's gaze and body movements provides a crucial source of information to successfully interact with other people, it remains unclear whether observers weigh differently these cues and whether the convergence of gaze and body's directions determines facilitation effects. Here we aim to shed more light on this issue by testing the reliance upon these cues from both a behavioral and a neurophysiological perspective in a social interactive context. In Experiment 1, we manipulated the convergence between the direction of an actor's upper limb movement and gaze direction while he attempts to socially interact with the participants observing the scene. We determined the direction of gaze as well as the duration of participants' ocular fixations during the observation of the scene. In Experiment 2, we measured and correlated the effect of the body/gaze manipulation on corticospinal excitability and on the readiness to interact—a disposition to engage in social situations. Eye-tracking data revealed that participants fixated chiefly the actor's head when his hand and gaze directions were divergent. Possibly a strategy to disambiguate the scene. Whereas participants mainly fixated the actor's hand when he performed an interactive request toward the participants. From a neurophysiological point of view, the more participants felt involved in the interaction, the lower was motor preparation in the muscle potentially needed to fulfill the actor's request. We contend that social contexts are more likely to elicit motor preparation compared to non-social ones, and that muscular inhibition is a necessary mechanism in order to prevent unwanted overt reactions during action observation tasks. [ABSTRACT FROM AUTHOR]

Locked-in syndrome (LIS) is a state of quadriplegia and anarthria with preserved consciousness, which is generally triggered by a disruption of specific white matter fiber tracts, following a lesion in the ventral part of the pons. However, the impact of focal lesions on the whole brain white matter microstructure and structural connectivity pathways remains unknown. We used diffusion tensor magnetic resonance imaging (DT-MRI) and tract-based statistics to characterise the whole white matter tracts in seven consecutive LIS patients, with ventral pontine injuries but no significant supratentorial lesions detected with morphological MRI. The imaging was performed in the acute phase of the disease (26 ± 13 days after the accident). DT-MRI-derived metrics were used to quantitatively assess global white matter alterations. All diffusion coefficient Z-scores were decreased for almost all fiber tracts in all LIS patients, with diffuse white matter alterations in both infratentorial and supratentorial areas. A mixture model of two multidimensional Gaussian distributions was fitted to cluster the white matter fiber tracts studied in two groups: the least (group 1) and most injured white matter fiber tracts (group 2). The greatest injuries were revealed along pathways crossing the lesion responsible for the LIS: left and right medial lemniscus (98.4% and 97.9% probability of belonging to group 2, respectively), left and right superior cerebellar peduncles (69.3% and 45.7% probability) and left and right corticospinal tract (20.6% and 46.5% probability). This approach demonstrated globally compromised white matter tracts in the acute phase of LIS, potentially underlying cognitive deficits. [ABSTRACT FROM AUTHOR]

Purpose: Aim of present study was to determine whether the currently recommended 13-cm cranio-caudal diameter cut-off on CT for assessment of splenic involvement in lymphoma offers adequate sensitivity and specificity. Materials and Methods: Patients with histologically proven lymphoma who had undergone [18F]FDG-PET/CT before therapy were included. Cranio-caudal diameters of the spleen were measured on the CT component of PET/CT, and ROC analyses with calculation of respective areas under the curve (AUC) were used to determine cut-off values of cranio-caudal measurements with their respective sensitivities and specificities, using [18F]FDG-PET as the reference standard. Results: In 93 patients, we found a sensitivity of 74.1% and a specificity of 47% for the 13-cm splenic diameter cut-off. Conclusions: Our results show reasonable, though far from perfect sensitivities and specificities for the currently recommend 13-cm splenic diameter cut-off. [ABSTRACT FROM AUTHOR]

Targeted neuromodulation strategies that strengthen neuronal activity are in great need for restoring sensorimotor function after chronic spinal cord injury (SCI). In this study, we established changes in the motoneuron output of individuals with and without SCI after repeated noninvasive transspinal stimulation at rest over the thoracolumbar enlargement, the spinal location of leg motor circuits. Cases of motor incomplete and complete SCI were included to delineate potential differences when corticospinal motor drive is minimal. All 10 SCI and 10 healthy control subjects received daily monophasic transspinal stimuli of 1-ms duration at 0.2 Hz at right soleus transspinal evoked potential (TEP) subthreshold and suprathreshold intensities at rest. Before and two days after cessation of transspinal stimulation, we determined changes in TEP recruitment input-output curves, TEP amplitude at stimulation frequencies of 0.1, 0.125, 0.2, 0.33 and 1.0 Hz, and TEP postactivation depression upon transspinal paired stimuli at interstimulus intervals of 60, 100, 300, and 500 ms. TEPs were recorded at rest from bilateral ankle and knee flexor/extensor muscles. Repeated transspinal stimulation increased the motoneuron output over multiple segments. In control and complete SCI subjects, motoneuron output increased for knee muscles, while in motor incomplete SCI subjects motoneuron output increased for both ankle and knee muscles. In control subjects, TEPs homosynaptic and postactivation depression were present at baseline, and were potentiated for the distal ankle or knee flexor muscles. TEPs homosynaptic and postactivation depression at baseline depended on the completeness of the SCI, with minimal changes observed after transspinal stimulation. These results indicate that repeated transspinal stimulation increases spinal motoneuron responsiveness of ankle and knee muscles in the injured human spinal cord, and thus can promote motor recovery. This noninvasive neuromodulation method is a promising modality for promoting functional neuroplasticity after SCI. [ABSTRACT FROM AUTHOR]

The corticospinal system and local spinal circuits control human bipedal locomotion. The primary motor cortex is phase-dependently activated during gait; this cortical input is critical for foot flexor activity during the swing phase. We investigated whether gait-combined rhythmic brain stimulation can induce neuroplasticity in the foot area of the motor cortex and alter gait parameters. Twenty-one healthy subjects participated in the single-blinded, cross-over study. Each subject received anodal transcranial patterned direct current stimulation over the foot area of the right motor cortex during gait, sham stimulation during gait, and anodal transcranial patterned direct current stimulation during rest in a random order. Six subjects were excluded due to a failure in the experimental recording procedure. Complete-case analysis was performed using the data from the remaining 15 subjects. Self-paced gait speed and left leg stride length were significantly increased after the stimulation during gait, but not after the sham stimulation during gait or the stimulation during rest. In addition, a significant increase was found in the excitability of the corticospinal pathway of the left tibialis anterior muscle 30 min after stimulation during gait. Anodal transcranial patterned direct current stimulation during gait entrained the gait cycle to enhance motor cortical activity in some subjects. These findings suggest that the stimulation during gait induced neuroplasticity in corticospinal pathways driving flexor muscles during gait. [ABSTRACT FROM AUTHOR]

Observing others’ actions desynchronizes electroencephalographic (EEG) rhythms and modulates corticospinal excitability as assessed by transcranial magnetic stimulation (TMS). However, it remains unclear if these measures reflect similar neurofunctional mechanisms at the individual level. In the present study, a within-subject experiment was designed to assess these two neurophysiological indexes and to quantify their mutual correlation. Participants observed reach-to-grasp actions directed towards a small (precision grip) or a large object (power grip). We focused on two specific time points for both EEG and TMS. The first time point (t1) coincided with the maximum hand aperture, i.e. the moment at which a significant modulation of corticospinal excitability is expected. The second (t2), coincided with the EEG resynchronization occurring at the end of the action, i.e. the moment at which a hypothetic minimum for action observation effect is expected. Results showed a Mu rhythm bilateral desynchronization at t1 with differential resynchronization at t2 in the two hemispheres. Beta rhythm was more desynchronized in the left hemisphere at both time points. These EEG differences, however, were not influenced by grip type. Conversely, motor potentials evoked by TMS in an intrinsic hand muscle revealed an interaction effect of grip and time. No significant correlations between Mu/Beta rhythms and motor evoked potentials were found. These findings are discussed considering the spatial and temporal resolution of the two investigated techniques and argue over two alternative explanations: i. each technique provides different measures of the same process or ii. they describe complementary features of the action observation network in humans. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) research has shown that corticospinal excitability is facilitated during the observation of human movement. However, the relationship between corticospinal excitability and participants’ visual attention during action observation is rarely considered. Nineteen participants took part in four conditions: (i) a static hand condition, involving observation of a right hand holding a ball between the thumb and index finger; (ii) a free observation condition, involving observation of the ball being pinched between thumb and index finger; and (iii and iv) finger-focused and ball-focused conditions, involving observation of the same ball pinch action with instructions to focus visual attention on either the index finger or the ball. Single-pulse TMS was delivered to the left motor cortex and motor evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) and abductor digiti minimi muscles of the right hand. Eye movements were recorded simultaneously throughout each condition. The ball-focused condition produced MEPs of significantly larger amplitude in the FDI muscle, compared to the free observation or static hand conditions. Furthermore, regression analysis indicated that the number of fixations on the ball was a significant predictor of MEP amplitude in the ball-focused condition. These results have important implications for the design and delivery of action observation interventions in motor (re)learning settings. Specifically, providing viewing instructions that direct participants to focus visual attention on task-relevant objects affected by the observed movement promotes activity in the motor system in a more optimal manner than free observation or no instructions. [ABSTRACT FROM AUTHOR]

Previous studies have shown modulation of corticospinal output of the agonist muscle when a known-movement is prepared but withheld until a response signal appearance, reflecting motor preparation processes. However, modulation in the antagonist muscles has not been described, despite the fact that reaching movements require precise coordination between the activation of agonist and antagonist muscles. In this study, participants performed an instructed-delay reaction time (RT) task, with randomized elbow flexion and extension movements. The aim was to assess the time course modulation of corticospinal output in two antagonist muscles, by simultaneously quantified the amplitude of motor evoked potentials (MEPs) in biceps brachii and triceps brachii, and the amplitude and direction of elbow movements evoked by transcranial magnetic stimulation (TMS). Depending on the prepared movement direction, a specific modulation of corticospinal output was observed, MEPs and TMS-evoked movements amplitude being relatively greater for extension compared to flexion. At the end of motor preparation, a decrease in MEPs amplitude was observed for both biceps brachii and triceps brachii, regardless of the prepared movement direction. In contrast, the probability of evoking movement in the flexion direction and the amplitude of TMS-evoked movement decreased at the end of preparation for flexion, but not for extension. Together, these results confirm the existence of inhibitory processes at the end of the motor preparation, probably to avoid a premature motor response. Moreover, they provide evidence of differences in the corticospinal control of elbow flexor and extensor muscles with patterns of modulation that are not necessarily reciprocal during motor preparation. [ABSTRACT FROM AUTHOR]

The object of this study was to clarify whether corticospinal excitability controlling hand muscles changes concurrently with increases in the imagined contraction level of foot dorsiflexion. Twelve participants performed actual and imagined dorsiflexion of their right foot at three different EMG levels (10, 40 or 80% of the maximum voluntary contraction). During isometric actual- or imagined- dorsiflexion, transcranial magnetic stimulation (TMS) was delivered to the right hand area of the left primary motor cortex. Motor evoked potentials (MEPs) were recorded from the right extensor carpi radialis (ECR) and flexor carpi radialis (FCR). During actual contraction, MEP amplitudes of ECR and FCR increased with an increased EMG level of dorsiflexion. Similarly, during imagery contraction, MEP amplitudes of ECR and FCR increased with the intensity of imagery contraction. Furthermore, a correlation between MEP amplitude during actual contraction and imagery contraction was observed for both ECR and FCR. Motor imagery of foot contraction induced an enhancement of corticospinal excitability for hand muscles that was dependent on the imagined contraction levels, just as what was observed when there was an actual contraction. [ABSTRACT FROM AUTHOR]

Background and purpose: Brain tumors in the corticospinal tract (CST) region are more likely to cause motor dysfunction. The aim of this study is to evaluate the effect of gliomas located in the CST region on motor function with diffusion tensor imaging (DTI) preoperatively. Materials and methods: Forty-five patients with histopathologically confirmed gliomas were included in this pilot study, in all cases (low-grade n = 13, high-grade n = 32) CST but not the motor cortex were involved by the tumor. DTI image were acquired and the posterior limb of the internal capsule fractional anisotropy (FA) and relative FA (rFA = affected FA/contralateral FA) were measured. Injury of the CST from tumor was divided into three grades (grade 1: displacement, grade 2: displacement and infiltration, grade 3: displacement and disruption). The fiber density index (FDi) and relative FDi (rFDi = affected FDi/contralateral FDi) of the injured and contralateral CST were measured. The correlations between muscle strength and the CST injury grade and the rFA, affected FDi, rFDi values were calculated using Spearman rank correlation analysis. rFA and rFDi values of muscle strength groups (MMT2-5) were compared with one-way analysis of variance (ANOVA). The difference of muscle strength between low- and high-grade glioma groups were analysed with the Mann-Whitney U-test. Results: Muscle strength was negatively correlated with the injury grade of the CST (r = -0.840, P<0.001). Muscle strength was positively correlated with rFA, FDi and rFDi (correlation coefficients (r) were 0.615, 0.643 and 0.567 for rFA, FDi and rFDi, respectively). The rFA values between grades (2&3, 2&4, 2&5, 3&5, 4&5) of muscle strength were significantly different (P<0.05), the rFDi values between grades (2&4, 2&5, 3&4, 3&5) of muscle strength were significantly different (P<0.05), while the rFA and rFDi values in the remaining groups of muscle strength grades showed no significant differences(P>0.05). Conclusions: Preoperative DTI and diffusion tensor tractography may quantify the injury degrees of CST and the extent of motor dysfunction in patients with brain glioma. [ABSTRACT FROM AUTHOR]

Several quantitative magnetic resonance imaging (MRI) techniques have been proposed to investigate microstructural tissue changes in amyotrophic lateral sclerosis (ALS) including diffusion tensor imaging (DTI), magnetization transfer imaging, and R2* mapping. Here, in this study, we compared these techniques with regard to their capability for detecting ALS related white matter (WM) changes in the brain and their association with clinical findings. We examined 27 ALS patients and 35 age-matched healthy controls. MRI was performed at 3T, after which we analyzed the diffusion properties, the magnetization transfer ratio (MTR), and the effective transversal relaxation rate R2* in 18 WM tracts that were obtained by a fully automated segmentation technique. ALS patients, especially with a bulbar onset, showed a bilateral increase in radial and mean diffusivity, as well as a reduction in fractional anisotropy of the corticospinal tract (CST), and diffusion changes in the parietal and temporal superior longitudinal fasciculus. A reduction of the MTR was found in both CSTs and an R2* reduction was seen only in the left CST. Tract-specific diffusion properties were not related to clinical status in a cross-sectional manner but demonstrated some association with disease progression over three subsequent months. DTI reveals more widespread WM tissue changes than MTR and R2*. These changes are not restricted to the CST, but affect also other WM tracts (especially in patients with bulbar onset), and are associated with the short term course of the disease. [ABSTRACT FROM AUTHOR]

Objectives: Muscular targets that are deep or inaccessible to surface electromyography (sEMG) require intrinsic recording using fine-wire electromyography (fEMG). It is unknown if fEMG validly record cortically evoked muscle responses compared to sEMG. The purpose of this investigation was to establish the validity and agreement of fEMG compared to sEMG to quantify typical transcranial magnetic stimulation (TMS) measures pre and post repetitive TMS (rTMS). The hypotheses were that fEMG would demonstrate excellent validity and agreement compared with sEMG. Materials and methods: In ten healthy volunteers, paired pulse and cortical silent period (CSP) TMS measures were collected before and after 1200 pulses of 1Hz rTMS to the motor cortex. Data were simultaneously recorded with sEMG and fEMG in the first dorsal interosseous. Concurrent validity (r and rho) and agreement (Tukey mean-difference) were calculated. Results: fEMG quantified corticospinal excitability with good to excellent validity compared to sEMG data at both pretest (r = 0.77–0.97) and posttest (r = 0.83–0.92). Pairwise comparisons indicated no difference between sEMG and fEMG for all outcomes; however, Tukey mean-difference plots display increased variance and questionable agreement for paired pulse outcomes. CSP displayed the highest estimates of validity and agreement. Paired pulse MEP responses recorded with fEMG displayed reduced validity, agreement and less sensitivity to changes in MEP amplitude compared to sEMG. Change scores following rTMS were not significantly different between sEMG and fEMG. Conclusion: fEMG electrodes are a valid means to measure CSP and paired pulse MEP responses. CSP displays the highest validity estimates, while caution is warranted when assessing paired pulse responses with fEMG. Corticospinal excitability and neuromodulatory aftereffects from rTMS may be assessed using fEMG. [ABSTRACT FROM AUTHOR]

We investigated whether stimulating the cerebellum and primary motor cortex (M1) using transcranial direct current stimulation (tDCS) could affect postural control in young and older adults. tDCS was employed using a double-blind, sham-controlled design, in which young (aged 18–35) and older adults (aged 65+) were assessed over three sessions, one for each stimulatory condition–M1, cerebellar and sham. The effect of tDCS on postural control was assessed using a sway-referencing paradigm, which induced platform rotations in proportion to the participant’s body sway, thus assessing sensory reweighting processes. Task difficulty was manipulated so that young adults experienced a support surface that was twice as compliant as that of older adults, in order to minimise baseline age differences in postural sway. Effects of tDCS on postural control were assessed during, immediately after and 30 minutes after tDCS. Additionally, the effect of tDCS on corticospinal excitability was measured by evaluating motor evoked potentials using transcranial magnetic stimulation immediately after and 30 minutes after tDCS. Minimal effects of tDCS on postural control were found in the eyes open condition only, and this was dependent on the measure assessed and age group. For young adults, stimulation had only offline effects, as cerebellar stimulation showed higher mean power frequency (MPF) of sway 30 minutes after stimulation. For older adults, both stimulation conditions delayed the increase in sway amplitude witnessed between blocks one and two until stimulation was no longer active. In conclusion, despite tDCS’ growing popularity, we would caution researchers to consider carefully the type of measures assessed and the groups targeted in tDCS studies of postural control. [ABSTRACT FROM AUTHOR]

Action video game playing is associated with improved visuomotor performance; however, the underlying neural mechanisms associated with this increased performance are not well understood. Using the Serial Reaction Time Task in conjunction with Transcranial Magnetic Stimulation, we investigated if improved visuomotor performance displayed in action video game players (actionVGPs) was associated with increased corticospinal plasticity in primary motor cortex (M1) compared to non-video game players (nonVGPs). Further, we assessed if actionVGPs and nonVGPs displayed differences in procedural motor learning as measured by the SRTT. We found that at the behavioral level, both the actionVGPs and nonVGPs showed evidence of procedural learning with no significant difference between groups. However, the actionVGPs displayed higher visuomotor performance as evidenced by faster reaction times in the SRTT. This observed enhancement in visuomotor performance amongst actionVGPs was associated with increased corticospinal plasticity in M1, as measured by corticospinal excitability changes pre- and post- SRTT and corticospinal excitability at rest before motor practice. Our results show that aVGPs, who are known to have better performance on visual and motor tasks, also display increased corticospinal excitability after completing a novel visuomotor task. [ABSTRACT FROM AUTHOR]

Patterned transcranial magnetic stimulation (TMS) such as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS) can induce changes in cortico-spinal excitability, commonly referred to as long-term potentiation (LTP)-like and long-term depression (LTD)-like effects in human motor cortex (M1). Here, we aimed to test the plasticity-inducing capabilities of a novel protocol that merged TBS and QPS. 360 bursts of quadri-pulse TBS (qTBS) were continuously given to M1 at 90% of active motor threshold (1440 full-sine pulses). In a first experiment, stimulation frequency of each burst was set to 666 Hz to mimic the rhythmicity of the descending cortico-spinal volleys that are elicited by TMS (i.e., I-wave periodicity). In a second experiment, burst frequency was set to 200 Hz to maximize postsynaptic Ca2+ influx using a temporal pattern unrelated to I-wave periodicity. The second phase of sinusoidal TMS pulses elicited either a posterior-anterior (PA) or anterior-posterior (AP) directed current in M1. Motor evoked potentials (MEPs) were recorded before and after qTBS to probe changes in cortico-spinal excitability. PA-qTBS at 666 Hz caused a decrease in PA-MEP amplitudes, whereas AP-qTBS at 666 Hz induced an increase in mean AP-MEP amplitudes. At a burst frequency of 200 Hz, PA-qTBS and AP-qTBS produced an increase in cortico-spinal excitability outlasting for at least 60 minutes in PA- and AP-MEP amplitudes, respectively. Continuous qTBS at 666 Hz or 200 Hz can induce lasting changes in cortico-spinal excitability. Induced current direction in the brain appears to be relevant when qTBS targets I-wave periodicity, corroborating that high-fidelity spike timing mechanisms are critical for inducing bi-directional plasticity in human M1. [ABSTRACT FROM AUTHOR]

Evidence suggests that motor experience plays a role in shaping development of the corticospinal system and voluntary motor control, which is a key motor function of the system. Here we used a mouse model with conditional forebrain deletion of the gene for EphA4 (Emx1-Cre:EphA4tm2Kldr), which regulates development of the laterality of corticospinal tract (CST). We combined study of Emx1-Cre:EphA4tm2Kldr with unilateral forelimb constraint during development to expand our understanding of experience-dependent CST development from both basic and translational perspectives. This mouse develops dense ipsilateral CST projections, a bilateral motor cortex motor representation, and bilateral motor phenotypes. Together these phenotypes can be used as readouts of corticospinal system organization and function and the changes brought about by experience. The Emx1-Cre:EphA4tm2Kldr mouse shares features with the common developmental disorder cerebral palsy: bilateral voluntary motor impairments and bilateral CST miswiring. Emx1-Cre:EphA4tm2Kldr mice with typical motor experiences during development display the bilateral phenotype of “mirror” reaching, because of a strongly bilateral motor cortex motor representation and a bilateral CST. By contrast, Emx1-Cre:EphA4tm2Kldr mice that experienced unilateral forelimb constraint from P1 to P30 and tested at maturity had a more contralateral motor cortex motor representation in each hemisphere; more lateralized CST projections; and substantially more lateralized/independent reaching movements. Changes in CST organization and function in this model can be explained by reduced synaptic competition of the CST from the side without developmental forelimb motor experiences. Using this model we show that unilateral constraint largely abrogated the effects of the genetic mutation on CST projections and thus demonstrates how robust and persistent experience-dependent development can be for the establishment of corticospinal system connections and voluntary control. Further, our findings inform the mechanisms of and strategies for developing behavioral therapies to treat bilateral movement impairments and CST miswiring in cerebral palsy. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) and essential tremor (ET) are characterized with motor dysfunctions. Motor circuit dysfunctions can be complementarily investigated by paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor imaging (DTI) of the corticospinal tract (CST). Three groups of twelve subjects with moderate severity PD, ET with intention tremor and healthy controls (HC) were studied. The primary motor cortex (M1) excitability, measured by motor evoked potential (MEP) amplitude and by short-interval and long-interval intracortical inhibition (SICI and LICI) was compared between the three groups before and after PAS. The DTI measures of fractional anisotropy (FA) and mean diffusivity (MD) were acquired. PAS effects and DTI data were simultaneously examined between groups. PAS increased MEP amplitude in HC but not in PD and ET. SICI and LICI were significantly reduced after PAS irrespective of groups. No significant differences of the mean FA and MD were found between groups. There was no significant correlation between the PAS effects and the DTI measures. Findings suggest that both PD and ET with intention tremor have impairment of the associative LTP-like corticospinal excitability change in M1. The microstructure of the CST is not relevant to the deficiency of M1 associative plasticity in PD and ET. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the involvement of the primary motor cortex (M1) in the coordination performance of karate athletes through transcranial magnetic stimulation (TMS). Methods: Thirteen right-handed male karate athletes (25.0±5.0 years) and 13 matched non-athlete controls (26.7±6.2 years) were enrolled. A single-pulse TMS was applied using a figure-eight coil stimulator. Resting motor threshold (rMT) was determined. Surface electromyography was recorded from the first dorsal interosseous muscle. Motor evoked potential (MEP) latencies and amplitudes at rMT, 110%, and 120% of rMT were considered. Functional assessment of the coordination performance was assessed by in-phase (IP) and anti-phase (AP) homolateral hand and foot coordination tasks performed at 80, 120, and 180 bpm. Results: Compared to controls, athletes showed lower rMT (p<0.01), shorter MEP latency (p<0.01) and higher MEP amplitude (p<0.01), with a significant correlation (r = 0.50, p<0.01) between rMT and MEP latency. Coordination decreased with increasing velocity, and better IP performances emerged compared to AP ones (p<0.001). In general, a high correlation between rMT and coordination tasks was found for both IP and AP conditions. Conclusion: With respect to controls, karate athletes present a higher corticospinal excitability indicating the presence of an activity-dependent alteration in the balance and interactions between inhibitory and facilitatory circuits determining the final output from the M1. Furthermore, the high correlation between corticospinal excitability and coordination performance could support sport-specific neurophysiological arrangements. [ABSTRACT FROM AUTHOR]

Several studies have used macaque monkeys with lesions induced in the primary motor cortex (M1) to investigate the recovery of motor function after brain damage. However, in human stroke patients, the severity and outcome of motor impairments depend on the degree of damage to the white matter, especially that in the posterior internal capsule, which carries corticospinal tracts. To bridge the gap between results obtained in M1-lesioned macaques and the development of clinical intervention strategies, we established a method of inducing focal infarcts at the posterior internal capsule of macaque monkeys by injecting endothelin-1 (ET-1), a vasoconstrictor peptide. The infarcts expanded between 3 days and 1 week after ET-1 injection. The infarct volume in each macaque was negatively correlated with precision grip performance 3 days and 1 week after injection, suggesting that the degree of infarct expansion may have been a cause of the impairment in hand movements during the early stage. Although the infarct volume decreased and gross movement improved, impairment of dexterous hand movements remained until the end of the behavioral and imaging experiments at 3 months after ET-1 injection. A decrease in the abundance of large neurons in M1, from which the descending motor tracts originate, was associated with this later-stage impairment. The present model is useful not only for studying neurological changes underlying deficits and recovery but also for testing therapeutic interventions after white matter infarcts in primates. [ABSTRACT FROM AUTHOR]

Following large strokes that encompass the cerebral cortex, it has been suggested that the corticospinal tract originating from the non-ischaemic hemisphere reorganises its pattern of terminal arborisation within the spinal cord to compensate for loss of function. However many strokes in humans predominantly affect subcortical structures with minimal involvement of the cerebral cortex. The aim of the present study was to determine whether remodelling of corticospinal terminals arising from the non-ischaemic hemisphere was associated with spontaneous recovery in rats with subcortical infarcts. Rats were subjected to transient middle cerebral artery occlusion or sham surgery and 28 days later, when animals exhibited functional recovery, cholera toxin b subunit was injected into the contralesional, intact forelimb motor cortex in order to anterogradely label terminals within cervical spinal cord segments. Infarcts were limited to subcortical structures and resulted in partial loss of corticospinal tract axons from the ischaemic hemisphere. Quantitative analysis revealed there was no significant difference in the numbers of terminals on the contralesional side of the spinal grey matter between ischaemic and sham rats. The results indicate that significant remodelling of the corticospinal tract from the non-ischaemic hemisphere is not associated with functional recovery in animals with subcortical infarcts. [ABSTRACT FROM AUTHOR]

Descending systems have a crucial role in the selection of motor output patterns by influencing the activity of interneuronal networks in the spinal cord. Commissural interneurons that project to the contralateral grey matter are key components of such networks as they coordinate left-right motor activity of fore and hind-limbs. The aim of this study was to determine if corticospinal (CST) and reticulospinal (RST) neurons make significant numbers of axonal contacts with cervical commissural interneurons. Two classes of commissural neurons were analysed: 1) local commissural interneurons (LCINs) in segments C4-5; 2) long descending propriospinal neurons (LDPNs) projecting from C4 to the rostral lumbar cord. Commissural interneurons were labelled with Fluorogold and CST and RST axons were labelled by injecting the b subunit of cholera toxin in the forelimb area of the primary somatosensory cortex or the medial longitudinal fasciculus respectively. The results show that LCINs and LDPNs receive few contacts from CST terminals but large numbers of contacts are formed by RST terminals. Use of vesicular glutamate and vesicular GABA transporters revealed that both types of cell received about 80% excitatory and 20% inhibitory RST contacts. Therefore the CST appears to have a minimal influence on LCINs and LDPNs but the RST has a powerful influence. This suggests that left-right activity in the rat spinal cord is not influenced directly via CST systems but is strongly controlled by the RST pathway. Many RST neurons have monosynaptic input from corticobulbar pathways therefore this pathway may provide an indirect route from the cortex to commissural systems. The cortico-reticulospinal-commissural system may also contribute to functional recovery following damage to the CST as it has the capacity to deliver information from the cortex to the spinal cord in the absence of direct CST input. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate cortical mechanisms upstream to the corticospinal motor neuron that may be associated with central fatigue and sense of effort during and after a fatigue task. We used two different isometric finger abduction protocols to examine the effects of muscle activation and fatigue the right first dorsal interosseous (FDI) of 12 participants. One protocol was intended to assess the effects of muscle activation with minimal fatigue (control) and the other was intended to elicit central fatigue (fatigue). We hypothesized that high frequency repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) would hasten recovery from central fatigue and offset a fatigue-induced increase in sense of effort by facilitating the primary motor cortex (M1). Constant force-sensation contractions were used to assess sense of effort associated with muscle contraction. Paired-pulse TMS was used to assess intracortical inhibition (ICI) and facilitation (ICF) in the active M1 and interhemispheric inhibitory (IHI) was assessed to determine if compensation occurs via the resting M1. These measures were made during and after the muscle contraction protocols. Corticospinal excitability progressively declined with fatigue in the active hemisphere. ICF increased at task failure and ICI was also reduced at task failure with no changes in IHI found. Although fatigue is associated with progressive reductions in corticospinal excitability, compensatory changes in inhibition and facilitation may act within, but not between hemispheres of the M1. rTMS of the SMA following fatigue enhanced recovery of maximal voluntary force and higher levels of ICF were associated with lower sense of effort following stimulation. rTMS of the SMA may have reduced the amount of upstream drive required to maintain motor output, thus contributing to a lower sense of effort and increased rate of recovery of maximal force. [ABSTRACT FROM AUTHOR]

Evidence suggests that the primary motor cortex (M1) is involved in both voluntary, goal-directed movements and in postural control. Trunk muscles are involved in both tasks, however, the extent to which M1 controls these muscles in trunk flexion/extension (voluntary movement) and in rapid shoulder flexion (postural control) remains unclear. The purpose of this study was to investigate this question by examining excitability of corticospinal inputs to trunk muscles during voluntary and postural tasks. Twenty healthy adults participated. Transcranial magnetic stimulation was delivered to the M1 to examine motor evoked potentials (MEPs) in the trunk muscles (erector spinae (ES) and rectus abdominis (RA)) during dynamic shoulder flexion (DSF), static shoulder flexion (SSF), and static trunk extension (STE). The level of background muscle activity in the ES muscles was matched across tasks. MEP amplitudes in ES were significantly larger in DSF than in SSF or in STE; however, this was not observed for RA. Further, there were no differences in levels of muscle activity in RA between tasks. Our findings reveal that corticospinal excitability of the ES muscles appears greater during dynamic anticipatory posture-related adjustments than during static tasks requiring postural (SSF) and goal-directed voluntary (STE) activity. These results suggest that task-oriented rehabilitation of trunk muscles should be considered for optimal transfer of therapeutic effect to function. [ABSTRACT FROM AUTHOR]

The magnitude and direction of reported physiological effects induced using transcranial magnetic stimulation (TMS) to modulate human motor cortical excitability have proven difficult to replicate routinely. We conducted an online survey on the prevalence and possible causes of these reproducibility issues. A total of 153 researchers were identified via their publications and invited to complete an anonymous internet-based survey that asked about their experience trying to reproduce published findings for various TMS protocols. The prevalence of questionable research practices known to contribute to low reproducibility was also determined. We received 47 completed surveys from researchers with an average of 16.4 published papers (95% CI 10.8–22.0) that used TMS to modulate motor cortical excitability. Respondents also had a mean of 4.0 (2.5–5.7) relevant completed studies that would never be published. Across a range of TMS protocols, 45–60% of respondents found similar results to those in the original publications; the other respondents were able to reproduce the original effects only sometimes or not at all. Only 20% of respondents used formal power calculations to determine study sample sizes. Others relied on previously published studies (25%), personal experience (24%) or flexible post-hoc criteria (41%). Approximately 44% of respondents knew researchers who engaged in questionable research practices (range 32–70%), yet only 18% admitted to engaging in them (range 6–38%). These practices included screening subjects to find those that respond in a desired way to a TMS protocol, selectively reporting results and rejecting data based on a gut feeling. In a sample of 56 published papers that were inspected, not a single questionable research practice was reported. Our survey revealed that approximately 50% of researchers are unable to reproduce published TMS effects. Researchers need to start increasing study sample size and eliminating—or at least reporting—questionable research practices in order to make the outcomes of TMS research reproducible. [ABSTRACT FROM AUTHOR]

Manganese-enhanced MRI (MEMRI) has been described as a powerful tool to depict the architecture of neuronal circuits. In this study we investigated the potential use of in vivo MRI detection of manganese for tracing neuronal projections from the primary motor cortex (M1) in healthy marmosets (Callithrix Jacchus). We determined the optimal dose of manganese chloride (MnCl2) among 800, 400, 40 and 8nmol that led to manganese-induced hyperintensity furthest from the injection site, as specific to the corticospinal tract as possible, and that would not induce motor deficit. A commonly available 3T human clinical MRI scanner and human knee coil were used to follow hyperintensity in the corticospinal tract 24h after injection. A statistical parametric map of seven marmosets injected with the chosen dose, 8 nmol, showed the corticospinal tract and M1 connectivity with the basal ganglia, substantia nigra and thalamus. Safety was determined for the lowest dose that did not induce dexterity and grip strength deficit, and no behavioral effects could be seen in marmosets who received multiple injections of manganese one month apart. In conclusion, our study shows for the first time in marmosets, a reliable and reproducible way to perform longitudinal ME-MRI experiments to observe the integrity of the marmoset corticospinal tract on a clinical 3T MRI scanner. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether hormonal fluctuations during the menstrual cycle affect corticospinal excitability, intracortical inhibition (ICI) or facilitation (ICF) in primary motor cortex, and also whether the hormonal fluctuations have any effect on manual dexterity in neurologically intact women. Materials and Methods: Twenty volunteers (10 Female, 10 Male) were included in this study. The levels of progesterone and estradiol were measured from saliva during the women’s menstrual follicular, ovulation and mid-luteal phases. Motor evoked potentials were recorded from the right first dorsal interosseous muscle. Single and paired-pulse Transcranial Magnetic Stimulation (TMS) were delivered in a block of 20 stimuli. With paired-pulse technique, 3ms and 10ms inter-stimulus intervals were used to assess ICI and ICF, respectively. The Grooved Pegboard Test (GPT) was completed in each session before the TMS assessments. Male participants were tested at similar time intervals as female participants. Results: Mixed design ANOVA revealed that GPT score in female participants was significantly lower at the mid-luteal phase compared to the ovulation phase (p = 0.017). However, it was not correlated with progesterone or estrogen fluctuations during the menstrual cycle. The results also showed that the effect of phase, sex and the interaction of phase by sex for resting motor threshold, ICI or ICF were not significant (p > 0.05). Conclusion: Manual dexterity performance fluctuates during the menstrual cycle in neurologically intact women, which might be due to the balance of the neuromodulatory effects of P4 and E2 in the motor cortex during different phases. [ABSTRACT FROM AUTHOR]

The aim is to investigate the effects of pulse duration (PD) on the modulatory effects of transcranial pulsed current (tPCS) on corticospinal excitability (CSE). CSE of the dominant primary motor cortex (M1) of right first dorsal interosseous muscle was assessed by motor evoked potentials, before, immediately, 10, 20 and 30 minutes after application of five experimental conditions: 1) anodal transcranial direct current stimulation (a-tDCS), 2) a-tPCS with 125 ms pulse duartion (a-tPCSPD = 125), 3) a-tPCS with 250 ms pulse duration (a-tPCSPD = 250), 4) a-tPCS with 500 ms pulse duration (a-tPCSPD = 500) and 5) sham a-tPCS. The total charges were kept constant in all experimental conditions except sham condition. Post-hoc comparisons indicated that a-tPCSPD = 500 produced larger CSE compared to a-tPCSPD = 125 (P<0.0001), a-tPCSPD = 250 (P = 0.009) and a-tDCS (P = 0.008). Also, there was no significant difference between a-tPCSPD = 250 and a-tDCS on CSE changes (P>0.05). All conditions except a-tPCSPD = 125 showed a significant difference to the sham group (P<0.006). All participants tolerated the applied currents. It could be concluded that a-tPCS with a PD of 500ms induces largest CSE changes, however further studies are required to identify optimal values. [ABSTRACT FROM AUTHOR]

Objective: The identification of the corticospinal tract (CST) pathway with a deterministic fiber tracking approach is limited because of crossing fibers, especially for the hand fibers of the CST due to the crossing superior longitudinal fasciculus (SLF). We examined a patient with congenital bilateral perisylvian syndrome (CBPS) who did not have the SLF, in order to visualize CST hand fibers that were not affected by crossing fibers. Methods: A 10-year-old girl without the SLF due to CBPS and three normal healthy subjects participated in this study. We used a deterministic fiber tracking algorithm, and the regions of interest (ROIs) were drawn in the posterior limb of internal capsule (PLIC) and the primary motor cortex. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR) were measured based on the extracted fiber tracts. Results: The ADC values were not different between the normal subjects and the patient with CBPS. The FA, RA, and VR values of the normal subjects were similar, but were relatively higher than those of the patient with CBPS. Conclusion: Our results clearly show the impact of the crossing fiber for the hand motor fibers of the CST pathway with deterministic tracking algorithms in diffusion tensor tractography. [ABSTRACT FROM AUTHOR]

Subdural cortical stimulation (SuCS) is an appealing method in the treatment of neurological disorders, and computational modeling studies of SuCS have been applied to determine the optimal design for electrotherapy. To achieve a better understanding of computational modeling on the stimulation effects of SuCS, the influence of anisotropic white matter conductivity on the activation of cortical neurons was investigated in a realistic head model. In this paper, we constructed pyramidal neuronal models (layers 3 and 5) that showed primary excitation of the corticospinal tract, and an anatomically realistic head model reflecting complex brain geometry. The anisotropic information was acquired from diffusion tensor magnetic resonance imaging (DT-MRI) and then applied to the white matter at various ratios of anisotropic conductivity. First, we compared the isotropic and anisotropic models; compared to the isotropic model, the anisotropic model showed that neurons were activated in the deeper bank during cathodal stimulation and in the wider crown during anodal stimulation. Second, several popular anisotropic principles were adapted to investigate the effects of variations in anisotropic information. We observed that excitation thresholds varied with anisotropic principles, especially with anodal stimulation. Overall, incorporating anisotropic conductivity into the anatomically realistic head model is critical for accurate estimation of neuronal responses; however, caution should be used in the selection of anisotropic information. [ABSTRACT FROM AUTHOR]

White matter tracts mature asymmetrically during development, and this development can be studied using diffusion magnetic resonance imaging. The aims of this study were i. to generate dynamic population-averaged white matter registration templates covering in detail the period from 25 weeks gestational age to term, and extending to 2 years of age based on DTI and fractional anisotropy, ii. to produce tract-specific probability maps of the corticospinal tracts, forceps major and forceps minor using probabilistic tractography, and iii. to assess the development of these tracts throughout this critical period of neurodevelopment. We found evidence for asymmetric development across the fiber bundles studied, with the corticospinal tracts showing earlier maturation (as measured by fractional anisotropy) but slower volumetric growth compared to the callosal fibers. We also found evidence for an anterior to posterior gradient in white matter microstructure development (as measured by mean diffusivity) in the callosal fibers, with the posterior forceps major developing at a faster rate than the anterior forceps minor in this age range. Finally, we report a protocol for delineating callosal and corticospinal fibers in extremely premature cohorts, and make available population-averaged registration templates and a probabilistic tract atlas which we hope will be useful for future neonatal and infant white-matter imaging studies. [ABSTRACT FROM AUTHOR]

As recently demonstrated, a placebo procedure in motor performance increases force production and changes the excitability of the corticospinal system, by enhancing the amplitude of the motor evoked potentials (MEP) and reducing the duration of the cortical silent period (CSP). However, it is not clear whether these neurophysiological changes are related to the behavioural outcome (increased force) or to a general effect of expectation. To clarify this, we investigated the nocebo effect, in which the induced expectation decreases force production. Two groups of healthy volunteers (experimental and control) performed a motor task by pressing a piston with the right index finger. To induce a nocebo effect in the experimental group, low frequency transcutaneous electrical nerve stimulation (TENS) was applied over the index finger with instructions of its detrimental effects on force. To condition the subjects, the visual feedback on their force level was surreptitiously reduced after TENS. Results showed that the experimental group reduced the force, felt weaker and expected a worse performance than the control group, who was not suggested about TENS. By applying transcranial magnetic stimulation over the primary motor cortex, we found that while MEP amplitude remained stable throughout the procedure in both groups, the CSP duration was shorter in the experimental group after the nocebo procedure. The CSP reduction resembled previous findings on the placebo effect, suggesting that expectation of change in performance diminishes the inhibitory activation of the primary motor cortex, independently of the behavioural outcome. [ABSTRACT FROM AUTHOR]

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than full-sine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the half-segment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior-anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS. [ABSTRACT FROM AUTHOR]

In this study, we investigated how modulation in corticospinal excitability elicited in the context of standing tasks varies as a function of age and between muscles. Changes in motor evoked potentials (MEPs) recorded in tibialis anterior (TA) and gastrocnemius lateralis (GL) were monitored while participants (young, n = 10; seniors, n = 11) either quietly stood (QS) or performed a heel raise (HR) task. In the later condition, transcranial magnetic stimulation (TMS) pulses were delivered at three specific time points during the task: 1) 250 ms before the “go” cue (preparatory (PREP) phase), 2) 100 ms before the heel rise (anticipatory postural adjustment (APA) phase), and 3) 200 ms after heel rise (execution (EXEC) phase). In each task and each phase, variations in MEP characteristics were analysed for age and muscle-dependent effects. Variations in silent period (SP) duration were also examined for certain phases (APA and EXEC). Our analysis revealed no major difference during QS, as participants exhibited very similar patterns of modulation in both TA and GL, irrespective of their age group. During the HR task, young adults exhibited a differential modulation in the PREP phase with enhanced responses in TA relative to GL, which was not seen in seniors. Finally, besides differences in MEP latency, age had little influence on MEP modulation during the APA and EXEC phases, where amplitude was largely a function of background muscle activity associated with each phase (i.e., APA: TA; EXEC: GL). No age or muscle effects were detected for SP measurements. Overall, our results revealed no major differences between young adults and healthy seniors in the ability to modulate corticospinal facilitation destined to ankle muscles during standing tasks, with maybe the exception of the ability to prime muscle synergies in the preparatory phase of action. [ABSTRACT FROM AUTHOR]

Objective: To investigate the underlying physiological mechanisms of the structural differences in gray matter (GM) and white matter (WM) associated with obesity in young Chinese adults. Materials and Methods: A total of 49 right-handed obese or overweight (n = 22, mean age 31.72±8.04 years) and normal weight (n = 27, mean age 29.04±7.32 years) Han Chinese individuals were recruited. All participants underwent voxel-based morphometry analysis of T1-weighted MRI and tract-based spatial statistics analysis of diffusion tensor imaging. Partial correlation analysis was performed between the physiological data obtained and the abnormal structural alterations. Results: In the OO group, GM atrophy occurred in the left prefrontal cortex, bilateral cingulate gyrus, and the right temporal lobe, while enlargement was observed in the bilateral putamen. WM atrophy was observed predominantly in the regions that regulate food intake, such as the bilateral basal ganglia, the right amygdala, and the left insula. The OO group exhibited lower fractional anisotropy (FA) in bilateral frontal corticospinal tracts and the right brainstem. Significant negative correlations were observed between FA values of those three clusters and BMI, and waist circumference, while the volume of bilateral putamen positively correlated with both BMI and waist circumference. High plasma LDL levels were correlated with low FA values in the right frontal corticospinal tract. Interestingly, the negative correlation was limited to male participants. Conclusions: Obesity-related alterations of GM and WM volumes were observed predominantly in food reward circuit, which may motivate abnormal dietary intake. Further, early elevated plasma LDL might contribute to low right frontal FA values of male adults, which requires further demonstration by larger-scale and longitudinal studies. [ABSTRACT FROM AUTHOR]