Transcranial Brain Research Articles

Efficacy of tRNS and 140Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation.

This study investigates the effect of corticospinal excitability during sham stimulation on the individual response to transcranial non-invasive brain stimulation (tNIBS). Thirty healthy young adults aged 24.2 ± 2.8 S.D. participated in the study. Sham, as well as 1mA of tRNS and 140Hz tACS stimulation were applied for 10min each at different sessions. The effect of each stimulation type was quantified by recording TMS-induced, motor evoked potentials (MEPs) before (baseline) and at fixed time points after stimulation (T0, T30, T60 min.). According to the individual response to sham stimulation at T0 in comparison to baseline MEPs, subjects were regarded as responder or non-responder to sham. Following, MEPs at T0, T30 and T60 after verum or sham stimulation were assessed with a repeated measures ANOVA with the within-subject factor stimulation (sham, tRNS, 140Hz tACS) and the between-subjects factor group (responder vs non-responder). We found that individuals who did not show immediately changes in excitability in sham stimulation sessions were the ones who responded to active stimulation conditions. On the other hand, individuals who responded to sham condition, by either increases or decreases in MEPS, did not respond to active verum stimulation. This result suggests that the presence or lack of responses to sham stimulation can provide a marker for how individuals will respond to tRNS/tACS and thus provide an explanation for the variability in interindividual response. The results of this study draw attention to the general reactivity of the brain, which can be taken into account when planning future studies using tNIBS.

Contraction intensity-dependent variations in the responses to brain and corticospinal tract stimulation after a single session of resistance training in men.

The aim of this study was to determine the effects of acute resistance training (RT) intensity on motor-evoked potentials (MEPs) generated by transcranial magnetic brain stimulation and on cervicomedullary motor-evoked potentials (CMEPs) produced by electrical stimulation of the corticospinal tract. In four experimental sessions, 14 healthy young men performed 12 sets of eight isometric contractions of the elbow flexors at 0 (Control session), 25, 50, and 75% of the maximal voluntary contraction (MVC). Before and after each session, MEPs, CMEPs, and the associated twitch forces were recorded at rest. MEPs increased by 39% (P < 0.05 versus 25% in the control condition, Effect size (ES) = 1.04 and 1.76, respectively) after the 50% session and by 70% (P < 0.05 vs. all other conditions, ES = 0.91-2.49) after the 75% session. In contrast, CMEPs increased similarly after the 25%, 50%, and 75% sessions with an overall increase of 27% (P < 0.05 vs. control condition, ES = 1.34). The amplitude of maximal compound muscle action potentials (Mmax) was unchanged during the experiment. The MEP- and CMEP-associated twitch forces also increased after RT, but training intensity affected only the increases in MEP twitch forces. The data tentatively suggest that the intensity of muscle contraction used in acute bouts of RT affects cortical excitability.NEW & NOTEWORTHY Resistance training (RT) can acutely increase the efficacy of the corticospinal-motoneuronal synapse, motoneuron excitability and motor cortical excitability. We show that motor-evoked potential generated by transcranial magnetic stimulation but not cervicomedullary electrical stimulation increased in proportion to the intensity of training used during a single session of RT. The data suggest that the intensity of muscle contraction used in acute bouts of RT affects cortical excitability.

A Robust Method for Adjustment of Laser Speckle Contrast Imaging during Transcranial Mouse Brain Visualization

Laser speckle imaging (LSI) is a well-known and useful approach for the non-invasive visualization of flows and microcirculation localized in turbid scattering media, including biological tissues (such as brain vasculature, skin capillaries etc.). Despite an extensive use of LSI for brain imaging, the LSI technique has several critical limitations. One of them is associated with inability to resolve a functionality of vessels. This limitation also leads to the systematic error in the quantitative interpretation of values of speckle contrast obtained for different vessel types, such as sagittal sinus, arteries, and veins. Here, utilizing a combined use of LSI and fluorescent intravital microscopy (FIM), we present a simple and robust method to overcome the limitations mentioned above for the LSI approach. The proposed technique provides more relevant, abundant, and valuable information regarding perfusion rate ration between different types of vessels that makes this method highly useful for in vivo brain surgical operations.

Neurophysiological examination combined with functional intraoperative navigation using TMS in patients with brain tumor near the central region-a pilot study.

Feasibility and value of non-invasive transcranial magnetic brain stimulation (TMS MAGVENTURE® MagPro R30 Denmark) for preoperative diagnosis and surgical planning of brain tumor operations in everyday clinical practice. A prospective monocentric study was conducted, which included preoperative neurological and electrophysiological examination, TMS, and display of functional data in the navigation system (LOCALITE® TMS Navigator Germany). During surgery, the TMS data were correlated with the intraoperative monitoring (IOM). Twenty-four hours to 96h and after at least 3months, follow-ups with neurological, electrophysiological examinations and TMS stimulation were performed. Twenty-five patients with tumors in or near by the primary motor cortex region were included in the study. Twenty-one patients completed preoperative and first postoperative TMS and the neurological examination. Eight of 21 patients showed slight worsening of primary motor cortex function, 8 patients had an unchanged state, and 4 patients showed an improvement early after surgery. The changes of the electrophysiological examination like significant delay of the latency and/or reduced amplitudes matched well with the postoperative neurological outcome: if patients showed a worsening of the SEP's and MEP's, the postoperative results revealed deterioration. A preoperatively performed TMS using the MAGVENTURE® MagPro R30 and the LOCALITE® TMS Navigator could be established in our clinical daily practice and allowed a safe and reliable mapping of the primary motor cortex in order to minimize the risk of postoperative neurological deficits and improve the neurological outcome of the patients.

Tracking Changes in Brain Network Connectivity under Transcranial Current Stimulation.

Noninvasive transcranial brain stimulation has been widely used in experimental and clinical applications to perturb the brain activity, aiming at promoting synaptic plasticity or enhancing functional connectivity within targeted brain regions. However, there are different types of neurostimulations and various choices of stimulation parameters; how these choices influence the intermediate neurophysiological effects and brain connectivity remain incompletely understood. We propose several quantitative methods to investigate the brain connectivity of an epileptic patient before and after transcranial alternating/direct current stimulation (tACS/tDCS). The neuro-feedback derived from our analyses may provide useful cues for the effectiveness of neurostimulation.

"ConnectToBrain" : Synergy project for therapeutic closed-loop stimulation of brain network disorders

Therapeutic non-invasive transcranial brain stimulation with previous treatment protocols showed at best moderate effect sizes and large interindividual variability with asubstantial proportion of non-responders. A currently intensively discussed approach to address these problems is individualized closed-loop stimulation. ConnectToBrain is asynergy project funded by the European Research Council to develop noninvasive closed-loop therapeutic stimulation of network disorders of the human brain.It consists of three main pillars: (1)development of amultichannel transcranial magnetic stimulation (mTMS) coil array that covers nearly all of the cerebral cortex and enables highly precise electronic control of location, direction, intensity and timing of the induced electrical fields, (2)development of real-time analysis of activity and connectivity in brain networks using electroencephalography (EEG) for instantaneous spatial and temporal control of stimulation (brain state-dependent, closed-loop stimulation) and adaptive optimization of treatment effects by machine learning and (3)translation of these neurotechnological innovations into physiological and clinical studies.

Cortical Excitability Dynamics During Fear Processing.

Background:Little is known about the modulation of cortical excitability in the prefrontal cortex during fear processing in humans. Here, we aimed to transiently modulate and test the cortical excitability during fear processing using transcranial magnetic stimulation (TMS) and brain oscillations in theta and alpha frequency bands with electroencephalography (EEG).Methods:We conducted two separate experiments (no-TMS and TMS). In the no-TMS experiment, EEG recordings were performed during the instructed fear paradigm in which a visual cue (CS+) was paired with an aversive unconditioned stimulus (electric shock), while the other visual cue was unpaired (CS-). In the TMS experiment, in addition the TMS was applied on the right dorsomedial prefrontal cortex (dmPFC). The participants also underwent structural MRI (magnetic resonance imaging) scanning and were assigned pseudo-randomly to both experiments, such that age and gender were matched. The cortical excitability was evaluated by time-frequency analysis and functional connectivity with weighted phase lag index (WPLI). We further linked the excitability patterns with markers of stress coping capability.Results:After visual cue onset, we found increased theta power in the frontal lobe and decreased alpha power in the occipital lobe during CS+ relative to CS- trials. TMS of dmPFC increased theta power in the frontal lobe and reduced alpha power in the occipital lobe during CS+. The TMS pulse increased the information flow from the sensorimotor region to the prefrontal and occipital regions in the theta and alpha bands, respectively during CS+ compared to CS-. Pre-stimulation frontal theta power (0.75–1 s) predicted the magnitude of frontal theta power changes after stimulation (1–1.25 s). Finally, the increased frontal theta power during CS+ compared to CS- was positively correlated with stress coping behavior.Conclusion:Our results show that TMS over dmPFC transiently modulated the regional cortical excitability and the fronto-occipital information flows during fear processing, while the pre-stimulation frontal theta power determined the strength of achieved effects. The frontal theta power may serve as a biomarker for fear processing and stress-coping responses in individuals and could be clinically tested in mental disorders.

Transcranial brain sonography for Parkinsonian syndromes.

Substantia nigra (SN) hyperechogenicity has been proved to be a characteristic finding for idiopathic Parkinson's disease (PD), occurring in more than 90% of the patients. This echofeature is owed to increased amounts of iron in the SN region and reflects a functional impairment of the nigrostriatal dopaminergic system. In a prospective blinded study in which a group of patients with early mild signs and symptoms of unclear Parkinsonism were followed until a definite clinical diagnosis of PD, the hyperechogenicity of the SN was demonstrated to be highly predictive of a final diagnosis of PD. For the diagnosis of PD in individuals with early motor symptoms, both the sensitivity and positive predictive value of SN hyperechogenicity were higher than 90% and both the specificity and negative predictive value were higher than 80%. For early differential diagnosis between PD and atypical Parkinsonian syndromes, the sensitivity and positive predictive value of SN hyperechogenicity were higher than 90%, and both the specificity and negative predictive value were higher than 80%. The diagnostic specificity is increased if combining the TCS findings of SN, lenticular nucleus and third ventricle. In asymptomatic adult subjects, SN hyperechogenicity, at least unilaterally, indicates a subclinical functional insufficiency of the nigrostriatal dopaminergic system. Recent papers revealed that SN hyperechogenicity might suggest preclinical PD. Reduced echogenicity of midbrain raphe indicates increased risk of depression in PD patients. Caudate nucleus hyperechogenicity has been associated with drug-induced psychosis, and frontal horn dilatation >20 mm with dementia. Transcranial brain sonography can be a valuable tool for managing patients with Parkinsonian signs and symptoms.

Reconstruction of Photoacoustic Tomography Inside a Scattering Layer Using a Matrix Filtering Method

Photoacoustic (PA) tomography (PAT) has potential for use in brain imaging due to its rich optical contrast, high acoustic resolution in deep tissue, and good biosafety. However, the skull often poses challenges for transcranial brain imaging. The skull can cause severe distortion and attenuation of the phase and amplitude of PA waves, which leads to poor resolution, low contrast, and strong noise in the images. In this study, we propose an image reconstruction method to recover the PA image insider a skull-like scattering layer. This method reduces the scattering artifacts by combining a correlation matrix filter and a time reversal operator. Both numerical simulations and PA imaging experiments demonstrate that the proposed approach effectively improves the image quality with less speckle noise and better signal-to-noise ratio. The proposed method may improve the quality of PAT in a complex acoustic scattering environment, such as transcranial brain imaging.

Noninvasive noncontact speckle contrast diffuse correlation tomography of cerebral blood flow in rats

Continuous and longitudinal imaging of cerebral blood flow (CBF) variations provide vital information to investigate pathophysiology and interventions for a variety of neurological and cerebral diseases. An innovative noncontact speckle contrast diffuse correlation tomography (scDCT) system was downscaled and adapted for noninvasive imaging of CBF distributions in rat brain through intact scalp and skull. Algorithms for 2D mapping and 3D image reconstruction of CBF distributions were developed and optimized. The continuous imaging capability of the system was shown by imaging global CBF increases during CO2 inhalations and regional CBF decreases across two hemispheres during sequential unilateral and bilateral common carotid artery ligations. The longitudinal imaging capability was demonstrated by imaging CBF variations over a long recovery period of 14 days after an acute stroke. Compared to the 2D mapping method, the 3D imaging method reduces partial volume effects, but needs more computation time for image reconstruction. Results from this study generally agree with those reported in the literature using similar protocols to induce CBF changes in rats. The scDCT enables a relatively large penetration depth (up to ∼10 mm), which is sufficient for transcranial brain measurements in small animals and human neonates. Ultimately, we expect to provide a noninvasive noncontact cerebral imager for basic neuroscience research in small animal models and clinical applications in human neonates.

S26. Transcranial Direct Current Stimulation in Obsessive-Compulsive Disorder: Electric Field Models and Considerations for the Optimal Montage of Electrodes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive transcranial brain stimulation (NTBS) approach. It has been studied as a treatment for Obsessive-Compulsive Disorder (OCD). As there are several candidate regions for targeting OCD relevant networks by NTBS, previous studies considerably vary in terms of electrode montages used. For guiding research on tDCS for OCD, we critically review the current evidence for different montages and their mechanistic actions hypothesized based on computational models of electric fields (EFs).

Weak electric fields promote resonance in neuronal spiking activity: Analytical results from two-compartment cell and network models.

Transcranial brain stimulation and evidence of ephaptic coupling have sparked strong interests in understanding the effects of weak electric fields on the dynamics of neuronal populations. While their influence on the subthreshold membrane voltage can be biophysically well explained using spatially extended neuron models, mechanistic analyses of neuronal spiking and network activity have remained a methodological challenge. More generally, this challenge applies to phenomena for which single-compartment (point) neuron models are oversimplified. Here we employ a pyramidal neuron model that comprises two compartments, allowing to distinguish basal-somatic from apical dendritic inputs and accounting for an extracellular field in a biophysically minimalistic way. Using an analytical approach we fit its parameters to reproduce the response properties of a canonical, spatial model neuron and dissect the stochastic spiking dynamics of single cells and large networks. We show that oscillatory weak fields effectively mimic anti-correlated inputs at the soma and dendrite and strongly modulate neuronal spiking activity in a rather narrow frequency band. This effect carries over to coupled populations of pyramidal cells and inhibitory interneurons, boosting network-induced resonance in the beta and gamma frequency bands. Our work contributes a useful theoretical framework for mechanistic analyses of population dynamics going beyond point neuron models, and provides insights on modulation effects of extracellular fields due to the morphology of pyramidal cells.

Transorbital alternating current stimulation modifies BOLD activity in healthy subjects and in a stroke patient with hemianopia: A 7 Tesla fMRI feasibility study

BackgroundModifying brain activity using non-invasive, low intensity transcranial electrical brain stimulation (TES) has rapidly increased during the past 20 years. Alternating current stimulation (ACS), for example, has been shown to alter brain rhythm activities and modify neuronal functioning in the visual system. Daily application of transorbital ACS to patients with optic nerve damage induces functional connectivity reorganization, and partially restores vision. While ACS is thought to mainly modify neuronal mechanisms, e.g. changes in brain oscillations that can be detected by EEG, it is still an open question, whether and how it may alter BOLD activity. ObjectiveWe evaluated whether transorbital ACS modulates BOLD activity in early visual cortex using high-resolution 7 Tesla functional magnetic resonance imaging (fMRI). MethodsIn this feasibility study transorbital ACS in the alpha range and sham ACS was applied in a random block design in five healthy subjects for 20 min at 1 mA. Brain activation in the visual areas V1, V2 and V3 were measured using 7 Tesla fMRI-based retinotopic mapping at the time points before (baseline) and after stimulation. In addition, we collected data from one hemianopic stroke patient with visual cortex damage after ten daily sessions with 25–50 min stimulation duration. ResultsIn healthy subjects transorbital ACS increased the activated cortical surface area, decreased the fMRI response amplitude and increased coherence in the visual cortex, which was most prominent in the full field task. In the patient, stimulation improved contrast sensitivity in the central visual field. BOLD amplitudes and coherence values were increased in most early visual areas in both hemispheres, with the most pronounced activation detected during eccentricity testing in retinotopic mapping. ConclusionsThis feasibility study showed that transorbital ACS modifies BOLD activity to visual stimulation, which outlasts the duration of the AC stimulation. This is in line with earlier neurophysiological findings of increased power in EEG recordings and functional connectivity reorganization in patients with impaired vision. Accordingly, the larger BOLD response area after stimulation can be explained by more coherent activation and lower variability in the activation. Alternatively, increased neuronal activity can also be taken into account. Controlled trials are needed to systematically evaluate the potential of repetitive transorbital ACS to improve visual function after visual pathway stroke and to determine the cause-effect relationship between neural and BOLD activity changes.

Impacts of the murine skull on high-frequency transcranial photoacoustic brain imaging.

Non-invasive photoacoustic tomography (PAT) of mouse brains with intact skulls has been a challenge due to the skull's strong acoustic attenuation, aberration, and reverberation, especially in the high-frequency range (>15 MHz). In this paper, we systematically investigated the impacts of the murine skull on the photoacoustic wave propagation and on the PAT image reconstruction. We studied the photoacoustic acoustic wave aberration due to the acoustic impedance mismatch at the skull boundaries and the mode conversion between the longitudinal wave and shear wave. The wave's reverberation within the skull was investigated for both longitudinal and shear modes. In the inverse process, we reconstructed the transcranial photoacoustic computed tomography (PACT) and photoacoustic microscopy (PAM) images of a point target enclosed by the mouse skull, showing the skull's different impacts on both modalities. Finally, we experimentally validated the simulations by imaging an in vitro mouse skull phantom using representative transcranial PAM and PACT systems. The experimental results agreed well with the simulations and confirmed the accuracy of our forward and inverse models. We expect that our results will provide better understanding of the impacts of the murine skull on transcranial photoacoustic brain imaging and pave the ways for future technical improvements.

A hierarchy of corticospinal plasticity in human hand and forearm muscles.

Key points Pairing stimulation of a finger flexor or extensor muscle at the motor point with transcranial magnetic stimulation (TMS) of the motor cortex generated plastic changes in motor output.Increases in output were greater in intrinsic hand muscles than in the finger flexor. No changes occurred in the finger extensor. This gradient was seen irrespective of which muscle was stimulated paired with transcranial magnetic stimulation.Intermittent theta‐burst stimulation also produced increases in output, although these were similar across muscles.We suggest that intrinsic hand and flexor muscles have a higher potential to show plasticity than extensors, although only when plasticity is induced by sensory input. This may relate to differences seen in recovery of function in these muscles after injury, such as post‐stroke. The ability of the motor system to show plastic change underlies skill learning and also permits recovery after injury. One puzzling observation is that, after stroke, upper limb flexor muscles show good recovery but extensors remain weak, with this being a major contributor to residual disability. We hypothesized that there might be differences in potential for plasticity across hand and forearm muscles. In the present study, we investigated this using two protocols based on transcranial magnetic brain stimulation (TMS) in healthy human subjects. Baseline TMS responses were recorded from two intrinsic hand muscles: flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC). In the first study, paired associative stimulation (PAS) was delivered by pairing motor point stimulation of FDS or EDC with TMS. Responses were then remeasured. Increases were greatest in the hand muscles, smaller in FDS and non‐significant in EDC, irrespective of whether stimulation of FDS or EDC was used. In the second study, intermittent theta‐burst rapid rate TMS was applied instead of PAS. In this case, all muscles showed similar increases in TMS responses. We conclude that the potential to show plastic changes in motor cortical output has the gradient: hand muscles > flexors > extensors. However, this was only seen in a protocol that requires integration of sensory input (PAS) and not when plasticity was induced purely by cortical stimulation (rapid rate TMS). This observation may relate to why functional recovery tends to favour flexor and hand muscles over extensors.

Motor learning enhanced by combined motor imagery and noninvasive brain stimulation is associated with reduced short-interval intracortical inhibition.

BackgroundMotor imagery (MI) improves motor skill learning, which is further enhanced when MI is paired with primary motor cortex transcranial brain stimulation or with electrical stimulation of the peripheral median nerve. Applying both stimulation types (here with 25 ms intervals) is called paired associative stimulation (PAS25). The final primary motor cortex output is determined by combined excitatory and intracortical inhibitory circuits, and reducing the latter is associated with enhanced synaptic transmission and efficacy. Indeed, short‐interval intracortical inhibition (SICI) inhibits motor evoked potentials (MEPs), and motor learning has been associated with decreased SICI and increased cortical excitability. Here, we investigated whether cortical excitability and SICI are altered by PAS25 applied after MI‐induced modulation of motor learning.MethodsPeak acceleration of a hand‐grasping movement and MEPs and SICI were measured before and after MI alone, PAS25 alone, and MI followed by PAS25 in 16 healthy participants to evaluate changes in motor learning, corticospinal excitability, and intracortical inhibition.ResultsAfter PAS25 alone, MEP amplitude increased while peak acceleration was unchanged. However, PAS25 applied following MI not only significantly enhanced both peak acceleration (p = 0.011) and MEP amplitude (p = 0.004) but also decreased SICI (p = 0.011). Moreover, we found that this decrease in SICI was significantly correlated with both the peak acceleration (r = 0.49, p = 0.029) and the MEP amplitude (r = 0.56, p = 0.013).ConclusionsThese results indicate that brain function altered by PAS25 of the motor cortex enhances MI‐induced motor learning and corticospinal excitability and decreases SICI, suggesting that SICI underlies, at least in part, PAS25 modulation of motor learning.

Modern approaches to diagnostics and treatment of migraine in children

This article reviews modern approaches to diagnostics and treatment of a very common and simultaneously underestimated and often maltreated disorder in children. It is fallacious management of migraine masked behind the diagnoses such as autonomic vessel dysfunction and vascular headache here in Ukraine. This is a tremendous problem and it should be solved with appropriate information spread across the medical community.&#x0D; Up-to-date classification according to the International Headache Society, diagnostic criteria, differential diagnosis, investigation and treatment strategies are presented in the article. All supported data are com-pliant with guidelines of developed countries with evidence-based medicine (US, Canada, Great Britain, Japan, Australia, New Zealand) enhanced with new trials and approved methods. Migraine management is a rapidly evolving concept, where major changes were done during recent years (transcranial Deep Brain Stimulation, vagus stimulation, CGRP-receptor mono-clonal antibodies).&#x0D; Considering disorder incidence and its impact on life quality and the existence of options for alleviating symptoms, this information is important for physicians who work with children, especially for general practitioners, pediatrics, pediatric and adult neurologists.

Is There a Future for Non-invasive Brain Stimulation as a Therapeutic Tool?

Several techniques and protocols of non-invasive transcranial brain stimulation (NIBS), including transcranial magnetic and electrical stimuli, have been developed in the past decades. These techniques can induce long lasting changes in cortical excitability by promoting synaptic plasticity and thus may represent a therapeutic option in neuropsychiatric disorders. On the other hand, despite these techniques have become popular, the fragility and variability of the after effects are the major challenges that non-invasive transcranial brain stimulation currentlyfaces. Several factors may account for such a variability such as biological variations, measurement reproducibility, and the neuronal state of the stimulated area. One possible strategy, to reduce this variability is to monitor the neuronal state in real time using EEG and trigger TMS pulses only at pre-defined state. In addition, another strategy under study is to use the spaced application of multiple NIBS protocols within a session to improve the reliability and extend the duration of NIBS effects. Further studies, although time consuming, are required for improving the so far limited effect sizes of NIBS protocols for treatment of neurological or psychiatric disorders.

Feeling stressed: are emotional reactions to stress affected by transcranial brain stimulation over the prefrontal cortex? A meta-analysis

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) over the prefrontal cortex positively affect cognitive control functions and stress-related symptoms. However, it has not yet been established to what extent prefrontal stimulation directly influences emotional reactions to stressful or adverse events.

The effects of non-invasive transcranial brain current stimulation (tDCS) on length trace over the unstable surface in healthy old individuals: a randomised double-blind sham-controlled crossover study

The effects of non-invasive transcranial brain current stimulation (tDCS) on length trace over the unstable surface in healthy old individuals: a randomised double-blind sham-controlled crossover study