Homeostatic metaplasticity induced by the combination of two inhibitory brain stimulation techniques: Continuous theta burst and transcranial static magnetic stimulation.

Aftereffects of non-invasive brain stimulation techniques may be brain state-dependent. Either continuous theta-burst stimulation (cTBS) as transcranial static magnetic field stimulation (tSMS) reduce cortical excitability. Our objective was to explore the aftereffects of tSMS on a M1 previously stimulated with cTBS. The interaction effect of two inhibitory protocols on cortical excitability was tested on healthy volunteers (n = 20), in two different sessions. A first application cTBS was followed by real-tSMS in one session, or sham-tSMS in the other session. When intracortical inhibition was tested with paired-pulse transcranial magnetic stimulation, LICI (ie., long intracortical inhibition) increased, although the unconditioned motor-evoked potential (MEP) remained stable. These effects were observed in the whole sample of participants regardless of the type of static magnetic field stimulation (real or sham) applied after cTBS. Subsequently, we defined a group of good-responders to cTBS (n = 9) on whom the unconditioned MEP amplitude reduced after cTBS and found that application of real-tSMS (subsequent to cTBS) increased the unconditioned MEP. This MEP increase was not found when sham-tSMS followed cTBS. The interaction of tSMS with cTBS seems not to take place at inhibitory cortical interneurons tested by LICI, since LICI was not differently affected after real and sham tSMS. Our results indicate the existence of a process of homeostatic plasticity when tSMS is applied after cTBS. This work suggests that tSMS aftereffects arise at the synaptic level and supports further investigation into tSMS as a useful tool to restore pathological conditions with altered cortical excitability.

Dual-Probe Transcranial Full-Waveform Inversion: A Brain Phantom Feasibility Study.

OBJECTIVE: Despite being a low-cost, portable and safe medical imaging technique, transcranial ultrasound imaging is not used widely in adults because of the severe degradation and distortion of signals caused by the skull. Full-waveform inversion (FWI) has recently been found to have potential as an effective method for transcranial ultrasound tomography to obtain high-quality, subwavelength-resolution acoustic models of the brain using low-frequency ultrasound data. In this study is the first demonstration of this method in recovering a high-resolution 2-D reconstruction of a brain and skull ultrasound imaging phantom using experimentally acquired data. METHODS: A 2:5 scale brain phantom encased within a 3-D-printed skull-mimicking layer was created to simulate a clinical transcranial imaging target. To obtain tomographic ultrasound data on the brain and skull phantom, a tomographic ultrasound acquisition system was designed and implemented using commercially available low-frequency cardiac probes. FWI reconstructions of the brain and skull phantom were performed using the acquired tomographic data and were compared with corresponding synthetic reconstructions. This comparison was used to evaluate the feasibility of the proposed imaging system when employing different transducer array configurations. RESULTS: We demonstrate the successful FWI reconstruction of the brain phantom within the skull mimic from experimentally acquired tomographic ultrasound data. To mitigate the effects of the skull-mimicking material, a reflection-matching algorithm was applied to model the morphology of the skull layer prior to performing the inversion. CONCLUSION: The findings of this study provide a promising step toward the clinical use of FWI for transcranial ultrasound imaging in adults.

Acute effects of a single neurodynamic mobilization session on range of motion and H-reflex in asymptomatic young subjects: A controlled study.

Neurodynamic techniques have yielded good clinical results in the treatment of various pathologies. The objective of this study is to examine the short-term effects of neurodynamic techniques of the sciatic nerve on hip ROM (range of motion) and on the amplitude and latency of the soleus H-reflex and M-waves, in young asymptomatic subjects. In a double-blind controlled trial design, 60 young asymptomatic participants were randomly assigned into six groups with different levels of manipulation of the sciatic nerve. The passive straight leg raise test was used to evaluate the hip ROM amplitude. All evaluations were performed before, 1 min after, and 30 min after intervention. For each time-point, spinal and muscle excitability were also tested. ROM increased in all groups, but none of the treatment groups had superior effects than the group with no treatment. This means that ROM testing maneuvers increased ROM amplitude, with no add-on effect of the proposed neurodynamic techniques. Neurophysiological responses changed similarly in all groups, showing that the aftereffects were not intervention-specific. We observed a significant negative association between the change in limb temperature and the change in latencies of all potentials. ROM-testing procedures performed repeatedly increase ROM amplitude. This observation should be considered when evaluating the aftereffects of therapeutic interventions on ROM amplitude. None of the explored neurodynamic techniques produced acute aftereffects on hip ROM amplitude, spinal or muscle excitability different to the induced by the ROM testing maneuver.

Adaptations of the Walking Corsi Test (WalCT) for 2- and 3-year-old preterm and term-born toddlers: A preliminary study.

Introduction: Topographical memory is crucial for navigation and environmental representation. The Walking Corsi Test (WalCT) has been used to evaluate topographical memory in children from 4 years upward. The present study aims to determine whether adapted versions of the WalCT- by simplifying instructions and increasing motivation- can be adopted to test topographical memory in 2- and 3-year-old toddlers born at term and preterm. Assessing this skill in such young children is important in light of recent studies that have shown how spatial cognition underlies the development of skills in other cognitive domains as well. Methods: For this purpose, 47 toddlers (27.39 ± 4.34 months, 38.3% females), 20 born at term and 27 preterm, performed two aimed-designed versions of WalCT. Results: The results showed better performance of the term groups with increasing age and for both versions. On the other hand, performance was better in 2-year-old term toddlers vs. preterm. When rising motivation, 2-year-old preterm toddlers improve their performance but differences between both groups were still significant. The preterm group showed lower performance related to lower levels of attention. Discussion: This study provides preliminary data on the suitability of the adapted versions of WalCT in early ages and prematurity conditions.

Synergistic effects of applying static magnetic fields and diazepam to improve EEG abnormalities in the pilocarpine epilepsy rat model.

The lithium-pilocarpine rat model is a well-known model of temporal epilepsy. Recently we found that transcranial static magnetic stimulation (tSMS) delay and reduce the signs of EEG in this model. We aim to test the effect of combining the therapeutic action of tSMS and diazepam, a drug used to treat status epilepticus. We induce epilepsy in 12 Sprague-Dawley rats. Animals were classified as "magnet" when a magnetic neodymium cylinder was placed over the skull or "control" when a stainless-steel replica was used. Diazepam was injected 60-min after the second doses of pilocarpine injection. We found a reduction in the number of spikes/minute for magnet condition compared with sham condition, reaching significance at 60 min after diazepam injection. The Root-Mean-Square shown a significant reduction in magnet animals compared with those receiving diazepam (Tukey's-test 30 and 60 min after diazepam injection, p < 0.01; 40 and 50 min after diazepam injection, p < 0.05). Furthermore, the power spectrum analysis shown a reduction in delta, theta, alpha and beta bands, on the diazepam + magnet animals compared to the diazepam + sham group. Analysis of high-frequency oscillations revealed an increased in the ripples due to pilocarpine being reduced by diazepam. Our results demonstrate that application of tSMS previously to diazepam potentiates the effect of the drug by reducing the electroencephalographic pattern associated with epileptiform discharges. We suggest a new synergistic cooperation between pharmacology and neuromodulation as a future treatment for epilepsy.

Stride: A flexible software platform for high-performance ultrasound computed tomography.

BACKGROUND AND OBJECTIVE: Advanced ultrasound computed tomography techniques like full-waveform inversion are mathematically complex and orders of magnitude more computationally expensive than conventional ultrasound imaging methods. This computational and algorithmic complexity, and a lack of open-source libraries in this field, represent a barrier preventing the generalised adoption of these techniques, slowing the pace of research, and hindering reproducibility. Consequently, we have developed Stride, an open-source Python library for the solution of large-scale ultrasound tomography problems. METHODS: On one hand, Stride provides high-level interfaces and tools for expressing the types of optimisation problems encountered in medical ultrasound tomography. On the other, these high-level abstractions seamlessly integrate with high-performance wave-equation solvers and with scalable parallelisation routines. The wave-equation solvers are generated automatically using Devito, a domain-specific language, and the parallelisation routines are provided through the custom actor-based library Mosaic. RESULTS: We demonstrate the modelling accuracy achieved by our wave-equation solvers through a comparison (1) with analytical solutions for a homogeneous medium, and (2) with state-of-the-art modelling software applied to a high-contrast, complex skull section. Additionally, we show through a series of examples how Stride can handle realistic numerical and experimental tomographic problems, in 2D and 3D, and how it can scale robustly from a local multi-processing environment to a multi-node high-performance cluster. CONCLUSIONS: Stride enables researchers to rapidly and intuitively develop new imaging algorithms and to explore novel physics without sacrificing performance and scalability. This will lead to faster scientific progress in this field and will significantly ease clinical translation.

Exploring the role of the left DLPFC in fatigue during unresisted rhythmic movements.

Understanding central fatigue during motor activities is important in neuroscience and different medical fields. The central mechanisms of motor fatigue are known in depth for isometric muscle contractions; however, current knowledge about rhythmic movements and central fatigue is rather scarce. In this study, we explored the role of an executive area (left dorsolateral prefrontal cortex [DLPFC]) in fatigue development during rhythmic movement execution, finger tapping (FT) at the maximal rate, and fatigue after effects on the stability of rhythmic patterns. Participants (n = 19) performed six sets of unresisted FT (with a 3 min rest in-between). Each set included four interleaved 30 s repetitions of self-selected (two repetitions) and maximal rate FT (two repetitions) without rest in-between. Left DLPFC involvement in the task was perturbed by transcranial static magnetic stimulation (tSMS) in two sessions (one real and one sham). Moreover, half of the self-selected FT repetitions were performed concurrently with a demanding cognitive task, the Stroop test. Compared with sham stimulation, real tSMS stimulation prevented waning in tapping frequency at the maximal rate without affecting perceived levels of fatigue. Participants' engagement in the Stroop test just prior to maximal FT reduced the movement amplitude during this mode of execution. Movement variability at self-selected rates increased during Stroop execution, especially under fatigue previously induced by maximal FT. Our results indicate cognitive-motor interactions and a prominent role of the prefrontal cortex in fatigue and the motor control of simple repetitive movement patterns. We suggest the need to approach motor fatigue including cognitive perspectives.

Spatial Response Identification Enables Robust Experimental Ultrasound Computed Tomography.

Ultrasound computed tomography techniques have the potential to provide clinicians with 3-D, quantitative and high-resolution information of both soft and hard tissues such as the breast or the adult human brain. Their practical application requires accurate modeling of the acquisition setup: the spatial location, orientation, and impulse response (IR) of each ultrasound transducer. However, the existing calibration methods fail to accurately characterize these transducers unless their size can be considered negligible when compared with the dominant wavelength, which reduces signal-to-noise ratios below usable levels in the presence of high-contrast tissues such as the skull. In this article, we introduce a methodology that can simultaneously estimate the location, orientation, and IR of the ultrasound transducers in a single calibration. We do this by extending spatial response identification (SRI), an algorithm that we have recently proposed to estimate transducer IRs. Our proposed methodology replaces the transducers in the acquisition device with a surrogate model whose effective response matches the experimental data by fitting a numerical model of wave propagation. This results in a flexible and robust calibration procedure that can accurately predict the behavior of the ultrasound acquisition device without ever having to know where the real transducers are or their individual IR. Experimental results using a ring acquisition system show that SRI produces calibrations of significantly higher quality than standard methodologies across all transducers, both in transmission and in reception. Experimental full-waveform inversion (FWI) reconstructions of a tissue-mimicking phantom demonstrate that SRI generates more accurate reconstructions than those produced with standard calibration techniques.

Hyperthermia-Induced Changes in EEG of Anesthetized Mice Subjected to Passive Heat Exposure.

Currently, the role of hypothermia in electroencephalography (EEG) is well-established. However, few studies have investigated the effect of hyperthermia on EEG, an important physiological parameter governing brain function. The aim of this work was to determine how neuronal activity in anesthetized mice is affected when the temperature rises above the physiological threshold mandatory to maintain the normal body functions. In this study, a temperature-elevation protocol, from 37 to 42°C, was applied to four female mice of 2-3 months old while EEG was recorded simultaneously. We found that hyperthermia reduces EEG amplitude by 4.36% when rising from 37 to 38 degrees and by 24.33% when it is increased to 42 degrees. Likewise, increasing the body temperature produces a very large impact on the EEG spectral parameters, reducing the frequency power at the delta, theta, alpha, and beta bands. Our results show that hyperthermia has a global effect on the EEG, being able to change the electrical activity of the brain.

Factors Related to Greater Functional Recovery after Suffering a Stroke.

BACKGROUND: In a stroke, the importance of initial functional status is fundamental for prognosis. The aim of the current study was to investigate functional status, assessed by the Functional Independence Measure (FIM) scale, and possible predictors of functional outcome at discharge from inpatient rehabilitation. METHODS: This is a retrospective study that was carried out at the Physical Medicine and Rehabilitation Service in A Coruña (Spain). A total of 365 consecutive patients with primary diagnosis of stroke were enrolled. The functional assessments of all patients were performed through the FIM. A descriptive and a bivariate analysis of the variables included in the study was made and a succession of linear regression models was used to determine which variables were associated with the total FIM at discharge. RESULTS: Prior to having the stroke, 76.7% were totally independent in activities of daily living. The FIM scale score was 52.5 ± 25.5 points at admission and 83.4 ± 26.3 at hospital discharge. The multivariate analysis showed that FIM scores on admission were the most important predictors of FIM outcomes. CONCLUSIONS: Our study indicates that the degree of independence prior to admission after suffering a stroke is the factor that will determine the functionality of patients at hospital discharge.

Peripheral-central interplay for fatiguing unresisted repetitive movements: a study using muscle ischaemia and M1 neuromodulation.

Maximal-rate rhythmic repetitive movements cannot be sustained for very long, even if unresisted. Peripheral and central mechanisms of fatigue, such as the slowing of muscle relaxation and an increase in M1-GABAb inhibition, act alongside the reduction of maximal execution rates. However, maximal muscle force appears unaffected, and it is unknown whether the increased excitability of M1 GABAergic interneurons is an adaptation to the waning of muscle contractility in these movements. Here, we observed increased M1 GABAb inhibition at the end of 30 s of a maximal-rate finger-tapping (FT) task that caused fatigue and muscle slowdown in a sample of 19 healthy participants. The former recovered a few seconds after FT ended, regardless of whether muscle ischaemia was used to keep the muscle slowed down. Therefore, the increased excitability of M1-GABAb circuits does not appear to be mediated by afferent feedback from the muscle. In the same subjects, continuous (inhibitory) and intermittent (excitatory) theta-burst stimulation (TBS) was used to modulate M1 excitability and to understand the underlying central mechanisms within the motor cortex. The effect produced by TBS on M1 excitability did not affect FT performance. We conclude that fatigue during brief, maximal-rate unresisted repetitive movements has supraspinal components, with origins upstream of the motor cortex.

Spatial Response Identification for Flexible and Accurate Ultrasound Transducer Calibration and its Application to Brain Imaging.

Accurate wave-equation modeling is becoming increasingly important in modern imaging and therapeutic ultrasound methodologies, such as ultrasound computed tomography, optoacoustic tomography, or high-intensity-focused ultrasound. All of them rely on the ability to accurately model the physics of wave propagation, including accurate characterization of the ultrasound transducers, the physical devices that are responsible for generating and recording ultrasound energy. However, existing methods fail to characterize the transducer response with the accuracy required to fully exploit the capabilities of these emerging imaging and therapeutic techniques. Consequently, we have designed a new algorithm for ultrasound transducer calibration and modeling: spatial response identification (SRI). This method introduces a parameterization of the ultrasound transducer and provides a method to calibrate the transducer model using experimental data, based on a formulation of the problem that is completely independent of the discretization chosen for the transducer or the number of parameters used. The proposed technique models the transducer as a linear time-invariant system that is spatially heterogeneous, and identifies the model parameters that are best at explaining the experimental data while honoring the full wave equation. SRI generates a model that can accommodate the complex, heterogeneous spatial response seen experimentally for ultrasound transducers. Experimental results show that SRI outperforms standard methods both in transmission and reception modes. Finally, numerical experiments using full-waveform inversion demonstrate that existing transducer-modeling approaches are insufficient to produce successful reconstructions of the human brain, whereas errors in our SRI algorithm are sufficiently small to allow accurate image reconstructions.

Effect of stimulation timing on testing voluntary muscle force generation.

BACKGROUND: The interpolated twitch technique (ITT) is a ubiquitous test for assessing the level of voluntary muscle force generation, in which muscle twitches are evoked via percutaneous electrical stimulation. Traditionally, the stimulation timing during the ITT is not computer-controlled and usually delivered from 5 to 10 s after the maximal voluntary contraction (MVC) of the potentiated muscle. METHODS: In this work, we evaluated the sizes of the evoked twitches in the lower limb with different controlled stimulation time delays with respect to the MVC of the ankle plantar flexors. Fifteen healthy participants were included. We recorded the un-potentiated muscle twitch amplitudes at rest in response to doublet supramaximal stimulation of the tibial nerve, superimposed twitches (SITs) at three different delays from the beginning of the MVC force plateau (0.1, 0.75, and 1.5 s), and resting twitches in the potentiated muscle at four different delays once the MVC was finished (0.1, 2.5, 5.0, and 10.0 s). RESULTS: The magnitude of the SITs did not vary among the delays tested but varied among the potentiated resting twitch (PRT) amplitudes, with 2.5 s being largest and 0.1 s being the smallest. Remarkably, the resting twitch amplitudes reduced during the session despite the long rest periods between MVCs (5 min). CONCLUSION: We conclude that proper control of the stimulation timing is mandatory to increase the sensitivity of the ITT, and a 2.5 s delay from the end of the MVC is recommended for the PRT. Controlling the development of fatigue, which can be intrinsic to testing with repeated MVCs, is also essential. We recommend reducing the number of MVC repetitions and increasing the rest periods between them.

Temporal dynamics of muscle, spinal and cortical excitability and their association with kinematics during three minutes of maximal-rate finger tapping.

We tested peripheral, spinal and cortical excitability during 3 minutes of unresisted finger tapping at the maximal possible rate, which induced fatigue. Subsequently, we studied the temporal dynamics of muscle fatigue, expressed in the tapping movement profile, and its relationship to neural systems using mixed model analyses. The tapping rate decreased by 40% over the duration of the task. The change in the amplitude of the range of motion was not significant. The excitability of the flexor and extensor muscles of the index finger was tested via evoked potentials obtained with various types of stimulation at various levels of the motor system. The change in spinal excitability with time was evaluated considering the simultaneous changes in muscle excitability; we also considered how spinal excitability changed over time to evaluate cortical excitability. Excitability in the flexor and extensor muscles at the different levels tested changed significantly, but similar excitability levels were observed at notably different tapping rates. Our results showed that only 33% of the decrease in the tapping rate was explained by changes in the excitability of the structures tested in the present work.

Effects of Transcranial Static Magnetic Stimulation on Motor Cortex Evaluated by Different TMS Waveforms and Current Directions.

Transcranial static magnetic stimulation (tSMS) modulates cortical excitability probably by interacting with the GABA-glutamate intracortical balance. Different transcranial magnetic stimulation (TMS) waveforms probe distinct GABA-mediated cortical inhibition networks. The goal of the present work is to further characterize tSMS-induced changes in motor cortex reactivity and inhibition-excitation (I/E) balance. We hypothesized that tSMS affects particular cortical networks and thus, the effects of tSMS would be different depending on the TMS waveform used to assess its results. 23 healthy young adults completed two sessions of real or sham tSMS. The order of the sessions was randomized across participants. Motor evoked potentials (MEPs), cortical silent period (CSP), short- and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were assessed with TMS monophasic posterior-anterior (monoPA; n = 9), monophasic anterior-posterior (monoAP; n = 7), or biphasic (biAP-PA; n = 7) pulses. Repeated measures analyses of variance and appropriate pairwise comparisons were performed for each TMS measure. After 15 min of real tSMS, the MEP amplitudes decreased compared to sham and baseline, SICI and LICI showed greater inhibition, and a tendency towards longer CSPs and less facilitation was found. These results were only observed with monoPA TMS. MEP amplitude increased compared to sham with monoAP TMS, with no clear changes in general intracortical I/E balance. Biphasic TMS was not able to capture any effects of tSMS. The results show that the effects of tSMS on cortical excitability and inhibition involve specific interneuron circuits that are selectively activated by monoPA TMS.

Static magnetic fields reduce epileptiform activity in anesthetized rat and monkey.

Increasing evidence indicates that static magnetic fields (SMF) reduce cortical activity in both human and animal models. The aim of this work was to investigate the effect of SMF on epileptiform cortical activity, a condition related to an abnormal increase in neuronal excitability. The first experimental block included a Pilocarpine rat model of epilepsy, in which a magnetic neodymium nickel-plated cylinder, a magnetic field of 0.5 T, or "sham" were placed over the skull. In the second experimental block, we recorded epileptic-like activity in the visual cortex of a monkey (Macaca mulatta) under control conditions and in the presence of the magnet. Between 15 and 30 minutes after the second dose of Pilocarpine, EEG changes compatible with seizure like events induced by Pilocarpine were clearly observed in the control animals (sham stimulation). Similar effects were visible in the animals exposed to the real magnet after 1-2 hours. In the monkey, SMF over the cortical focus clearly reduced abnormal activity: the intensity threshold for visual induction increased and the severity and duration decreased. These results reinforce the view that static magnets modulate cortical activity and open the door to the future therapeutic use of SMF in epilepsy as a complement to current pharmacological treatments.

Publisher Correction: Effects of a Finger Tapping Fatiguing Task on M1-Intracortical Inhibition and Central Drive to the Muscle.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Effects of a Finger Tapping Fatiguing Task on M1-Intracortical Inhibition and Central Drive to the Muscle.

The central drive to the muscle reduces when muscle force wanes during sustained MVC, and this is generally considered the neurophysiological footprint of central fatigue. The question is if force loss and the failure of central drive to the muscle are responsible mechanisms of fatigue induced by un-resisted repetitive movements. In various experimental blocks, we validated a 3D-printed hand-fixation system permitting the execution of finger-tapping and maximal voluntary contractions (MVC). Subsequently, we checked the suitability of the system to test the level of central drive to the muscle and developed an algorithm to test it at the MVC force plateau. Our main results show that the maximum rate of finger-tapping dropped at 30 s, while the excitability of inhibitory M1-intracortical circuits and corticospinal excitability increased (all by approximately 15%). Furthermore, values obtained immediately after finger-tapping showed that MVC force and the level of central drive to the muscle remained unchanged. Our data suggest that force and central drive to the muscle are not determinants of fatigue induced by short-lasting un-resisted repetitive finger movements, even in the presence of increased inhibition of the motor cortex. According to literature, this profile might be different in longer-lasting, more complex and/or resisted repetitive movements.