Visual evoked magnetic responses (VEMR) to flash and pattern reversal stimulation

The problems of using a single channel magnetometer (BTi, Model 601) in an unshielded clinical environment to measure visual evoked magnetic responses (VEMR) were studied. VEMR to flash and pattern reversal stimuli were measured in 100 normal subjects. Two components, the P100M to pattern reversal and P2M to flash, were measured successfully in the majority of patients. The mean latencies of these components in different decades of life were more variable than the visual evoked potentials (VEP) that have been recorded to these stimuli. The latency of the P100M appeared to increase significantly after about 55 years of age whereas little change occurred for the flash P2M. The effects of blur, check size, stimulus size and luminance intensity on the latency and amplitude of the VEMR were studied. Blurring a small (32') check significantly increased latency whereas blurring a large (70') check had little effect on latency. Increasing check size significantly reduced latency of the P100M but had little effect on amplitude. Increasing the field size decreases the latency and increases the amplitude of the P100M. Within a normal subject, most of the temporal variability of the P100M appeared to be associated with run to run variation rather than between recording sessions on the same day or between days. Reproducibility of the P100M was improved to a degree by employing a magnetically shielded room. Increasing flash intensity decreases the latency and increases the amplitude of the P2M component. The magnitude of the effects of varying stimulus parameters on the VEMR were frequently greater than is normally seen in the VEP. The topography of the P100M and P2M varied over the scalp in normal subjects. Full field responses to a large check could be explained as approximately the sum of the half field responses and were consistent with the cruciform model of the visual cortex. Preliminary source localisation data suggested a shallower source in the visual cortex for the flash P2M compared with the P100M. The data suggest that suitable protocols could be devised to obtain normative data of sufficient quality to use the VEMR to flash and pattern clinically.

Astrocyte-neuron signalling by synaptic stimulation in the ventrobasal thalamus

In the Ventrobasal (VB) thalamus, astrocytes are known to elicit NMDA-receptor mediated slow inward currents (SICs) spontaneously in neurons. Fluorescence imaging of astrocytes and patch clamp recordings from the thalamocortical (TC) neurons in the VB of 6-23 day old Wistar rats were performed. TC neurons exhibit spontaneous SICs at low frequencies (~0.0015Hz) that were inhibited by NMDA-receptor antagonists D-AP5 (50µM), and were insensitive to TTX (1µM) suggesting a non-neuronal origin. The effect of corticothalamic (CT) and sensory (Sen) afferent stimulation on astrocyte signalling was assessed by varying stimulus parameters. Moderate synaptic stimulation elicited astrocytic Ca2+ increases, but did not affect the incidence of spontaneous SICs. Prolonged synaptic stimulation induced a 265% increase in SIC frequency. This increase lasted over one hour after the cessation of synaptic stimulation, so revealing a Long Term Enhancement (LTE) of astrocyte-neuron signalling. LTE induction required group I mGluR activation. LTE SICs targeted NMDA-receptors located at extrasynaptic sites. LTE showed a developmental profile: from weeks 1-3, the SIC frequency was increased by an average 50%, 240% and 750% respectively. Prolonged exposure to glutamate (200µM) increased spontaneous SIC frequency by 1800%. This “chemical” form of LTE was prevented by the broad-spectrum excitatory amino acid transporter (EAAT) inhibitor TBOA (300µM) suggesting that glutamate uptake was a critical factor. My results therefore show complex glutamatergic signalling interactions between astrocytes and neurons. Furthermore, two previously unrecognised mechanisms of enhancing SIC frequency are described. The synaptically induced LTE represents a form of non-synaptic plasticity and a glial “memory” of previous synaptic activity whilst enhancement after prolonged glutamate exposure may represent a pathological glial signalling mechanism.

Methodology of photic stimulation revisited:updated European algorithm for visual stimulation in the EEG laboratory

Intermittent photic stimulation (IPS) is a common procedure performed in the electroencephalography (EEG) laboratory in children and adults to detect abnormal epileptogenic sensitivity to flickering light (i.e., photosensitivity). In practice, substantial variability in outcome is anecdotally found due to the many different methods used per laboratory and country. We believe that standardization of procedure, based on scientific and clinical data, should permit reproducible identification and quantification of photosensitivity. We hope that the use of our new algorithm will help in standardizing the IPS procedure, which in turn may more clearly identify and assist monitoring of patients with epilepsy and photosensitivity. Our algorithm goes far beyond that published in 1999 (Epilepsia, 1999a, 40, 75; Neurophysiol Clin, 1999b, 29, 318): it has substantially increased content, detailing technical and logistical aspects of IPS testing and the rationale for many of the steps in the IPS procedure. Furthermore, our latest algorithm incorporates the consensus of repeated scientific meetings of European experts in this field over a period of 6 years with feedback from general neurologists and epileptologists to improve its validity and utility. Accordingly, our European group has provided herein updated algorithms for two different levels of methodology: (1) requirements for defining photosensitivity in patients and in family members of known photosensitive patients and (2) requirements for tailored studies in patients with a clear history of visually induced seizures or complaints, and in those already known to be photosensitive.

Investigating central mechanisms underlying the effects of action observation and imagery through transcranial magnetic stimulation

Sport and exercise psychologists provide some interventions for clients based on limited direct evidence and partial understanding of the mechanisms that underpin their efficacy. The authors review a recent technique, transcranial magnetic stimulation (TMS), which offers a tested procedure for investigating cortical activity during observation and imagery processes. They provide a detailed description of the TMS protocol and highlight some of the key studies that inform sport and exercise psychology research. Finally, the authors offer some thoughts on the direct application to practice.

Transcranial magnetic stimulation reveals modulation of corticospinal excitability when observing actions with the intention to imitate

Studies using transcranial magnetic stimulation have demonstrated that action observation can modulate the activity of the corticospinal system. This has been attributed to the activity of an 'action observation network', whereby premotor cortex activity influences corticospinal excitability. Neuroimaging studies have demonstrated that the context in which participants observe actions (i.e. whether they simply attend to an action, or observe it with the intention to imitate) modulates action observation network activity. The study presented here examined whether the context in which actions were observed revealed similar modulatory effects on corticospinal excitability. Eight human participants observed a baseline stimulus (a fixation cross), observed actions in order to attend to them, or observed the same actions with the intention to imitate them. Whereas motor evoked potentials elicited from the first dorsal interosseus muscle of the hand were facilitated by attending to actions, observing the same actions in an imitative capacity led to no facilitation effect. Furthermore, no motor facilitation effects occurred in a control muscle. Electromyographic data collected when participants physically imitated the observed actions revealed that the activity of the first dorsal interosseus muscle increased significantly during action execution compared with rest. These data suggest that an inhibitory mechanism acts on the corticospinal system to prevent the immediate overt imitation of observed actions. These data provide novel insight into the properties of the human action observation network, demonstrating for the first time that observing actions with the intention to imitate them can modulate the effects of action observation on corticospinal excitability.

Reflecting on mirror mechanisms:motor resonance effects during action observation only present with low-intensity transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) studies indicate that the observation of other people's actions influences the excitability of the observer's motor system. Motor evoked potential (MEP) amplitudes typically increase in muscles which would be active during the execution of the observed action. This 'motor resonance' effect is thought to result from activity in mirror neuron regions, which enhance the excitability of the primary motor cortex (M1) via cortico-cortical pathways. The importance of TMS intensity has not yet been recognised in this area of research. Low-intensity TMS predominately activates corticospinal neurons indirectly, whereas high-intensity TMS can directly activate corticospinal axons. This indicates that motor resonance effects should be more prominent when using low-intensity TMS. A related issue is that TMS is typically applied over a single optimal scalp position (OSP) to simultaneously elicit MEPs from several muscles. Whether this confounds results, due to differences in the manner that TMS activates spatially separate cortical representations, has not yet been explored. In the current study, MEP amplitudes, resulting from single-pulse TMS applied over M1, were recorded from the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles during the observation of simple finger abductions. We tested if the TMS intensity (110% vs. 130% resting motor threshold) or stimulating position (FDI-OSP vs. ADM-OSP) influenced the magnitude of the motor resonance effects. Results showed that the MEP facilitation recorded in the FDI muscle during the observation of index-finger abductions was only detected using low-intensity TMS. In contrast, changes in the OSP had a negligible effect on the presence of motor resonance effects in either the FDI or ADM muscles. These findings support the hypothesis that MN activity enhances M1 excitability via cortico-cortical pathways and highlight a methodological framework by which the neural underpinnings of action observation can be further explored. © 2013 Loporto et al.

Context matters:combined influence of participation and intellectual stimulation on the promotion-focus/employee creativity relationship

In this paper, we examined the interactive effects of two contexts—participation and intellectual stimulation, and promotion focus on creativity. On the basis of a multi-organization sample of 213 employees, we tested and found that although promotion focus was positively related to creativity, the relationship between promotion focus and creativity was most positive when both participation and leader intellectual stimulation were high. We discuss the way contexts in combination influence employee creativity for promotion-oriented individuals, through increasing decision latitude as well as stimulating and promoting creativity. Copyright © 2011 John Wiley & Sons, Ltd.

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibithumanmotor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function. © 2013 the authors.

Inter-individual variability in optimal current direction for transcranial magnetic stimulation of the motor cortex

We evaluated inter-individual variability in optimal current direction for biphasic transcranial magnetic stimulation (TMS) of the motor cortex. Motor threshold for first dorsal interosseus was detected visually at eight coil orientations in 45° increments. Each participant (n = 13) completed two experimental sessions. One participant with low test–retest correlation (Pearson's r < 0.5) was excluded. In four subjects, visual detection of motor threshold was compared to EMG detection; motor thresholds were very similar and highly correlated (0.94–0.99). Similar with previous studies, stimulation in the majority of participants was most effective when the first current pulse flowed towards postero-lateral in the brain. However, in four participants, the optimal coil orientation deviated from this pattern. A principal component analysis using all eight orientations suggests that in our sample the optimal orientation of current direction was normally distributed around the postero-lateral orientation with a range of 63° (S.D. = 13.70°). Whenever the intensity of stimulation at the target site is calculated as a percentage from the motor threshold, in order to minimize intensity and side-effects it may be worthwhile to check whether rotating the coil 45° from the traditional posterior–lateral orientation decreases motor threshold.

Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

A simulation of the surface EMG for analysis of muscle activity during whole body vibratory stimulation

Many studies have accounted for whole body vibration effects in the fields of exercise physiology, sport and rehabilitation medicine. Generally, surface EMG is utilized to assess muscular activity during the treatment; however, large motion artifacts appear superimposed to the raw signal, making sEMG recording not suitable before any artifact filtering. Sharp notch filters, centered at vibration frequency and at its superior harmonics, have been used in previous studies, to remove the artifacts. [6, 10] However, to get rid of those artifacts some true EMG signal is lost. The purpose of this study was to reproduce the effect of motor-unit synchronization on a simulated surface EMG during vibratory stimulation. In addition, authors mean to evaluate the EMG power percentage in those bands in which are also typically located motion artifact components. Model characteristics were defined to take into account two main aspect: the muscle MUs discharge behavior and the triggering effects that appear during local vibratory stimulation. [7] Inter-pulse-interval, was characterized by a polimodal distribution related to the MU discharge frequency (IPI 55-80ms, σ=12ms) and to the correlation with the vibration period within the range of ±2 ms due to vibration stimulus. [1, 7] The signals were simulated using different stimulation frequencies from 30 to 70 Hz. The percentage of the total simulated EMG power within narrow bands centered at the stimulation frequency and its superior harmonics (± 1 Hz) resulted on average about 8% (± 2.85) of the total EMG power. However, the artifact in those bands may contain more than 40% of the total power of the total signal. [6] Our preliminary results suggest that the analysis of the muscular activity of muscle based on raw sEMG recordings and RMS evaluation, if not processed during vibratory stimulation may lead to a serious overestimation of muscular response.

Simulation of surface EMG for the analysis of muscle activity during whole body vibratory stimulation

This study aims to reproduce the effect of motor-unit synchronization on surface EMG recordings during vibratory stimulation to highlight vibration evoked muscle activity. The authors intended to evaluate, through numerical simulations, the changes in surface EMG spectrum in muscles undergoing whole body vibration stimulation. In some specific bands, in fact, vibration induced motion artifacts are also typically present. In addition, authors meant to compare the simulated EMGs with respect to real recordings in order to discriminate the effect of synchronization of motor units discharges with vibration frequencies from motion artifacts. Computations were performed using a model derived from previous studies and modified to consider the effect of vibratory stimulus, the motor unit synchronization and the endplates-electrodes relative position on the EMG signal. Results revealed that, in particular conditions, synchronization of MUs' discharge generates visible peaks at stimulation frequency and its harmonics. However, only a part of the total power of surface EMGs might be enclosed within artifacts related bands (±1. Hz centered at the stimulation frequency and its superior harmonics) even in case of strong synchronization of motor units discharges with the vibratory stimulus. © 2013 Elsevier Ireland Ltd.

Application of ensemble averaging to the analysis of electromyography recordings under whole body vibratory stimulation

The aim of this study is to evaluate the application of ensemble averaging to the analysis of electromyography recordings under whole body vibratory stimulation. Recordings from Rectus Femoris, collected during vibratory stimulation at different frequencies, are used. Each signal is subdivided in intervals, which time duration is related to the vibration frequency. Finally the average of the segmented intervals is performed. By using this method for the majority of the recordings the periodic components emerge. The autocorrelation of few seconds of signals confirms the presence of a pseudosinusoidal components strictly related to the soft tissues oscillations caused by the mechanical waves. © 2014 IEEE.

Selection of conserved epitopes from hepatitis C virus for pan-populational stimulation of T-cell responses

The hepatitis C virus (HCV) is able to persist as a chronic infection, which can lead to cirrhosis and liver cancer. There is evidence that clearance of HCV is linked to strong responses by CD8 cytotoxic T lymphocytes (CTLs), suggesting that eliciting CTL responses against HCV through an epitope-based vaccine could prove an effective means of immunization. However, HCV genomic plasticity as well as the polymorphisms of HLA I molecules restricting CD8 T-cell responses challenges the selection of epitopes for a widely protective vaccine. Here, we devised an approach to overcome these limitations. From available databases, we first collected a set of 245 HCV-specific CD8 T-cell epitopes, all known to be targeted in the course of a natural infection in humans. After a sequence variability analysis, we next identified 17 highly invariant epitopes. Subsequently, we predicted the epitope HLA I binding profiles that determine their potential presentation and recognition. Finally, using the relevant HLA I-genetic frequencies, we identified various epitope subsets encompassing 6 conserved HCV-specific CTL epitopes each predicted to elicit an effective T-cell response in any individual regardless of their HLA I background. We implemented this epitope selection approach for free public use at the EPISOPT web server. © 2013 Magdalena Molero-Abraham et al.

Brain activity modifications following spinal cord stimulation for chronic neuropathic pain:a systematic review

Background and objective: Spinal cord stimulation (SCS) is believed to exert supraspinal effects; however, these mechanisms are still far from fully elucidated. This systematic review aims to assess existing neurophysiological and functional neuroimaging literature to reveal current knowledge regarding the effects of SCS for chronic neuropathic pain on brain activity, to identify gaps in knowledge, and to suggest directions for future research. Databases and data treatment: Electronic databases and hand-search of reference lists were employed to identify publications investigating brain activity associated with SCS in patients with chronic neuropathic pain, using neurophysiological and functional neuroimaging techniques (fMRI, PET, MEG, EEG). Studies investigating patients with SCS for chronic neuropathic pain and studying brain activity related to SCS were included. Demographic data (age, gender), study factors (imaging modality, patient diagnoses, pain area, duration of SCS at recording, stimulus used) and brain areas activated were extracted from the included studies. Results: Twenty-four studies were included. Thirteen studies used neuroelectrical imaging techniques, eight studies used haemodynamic imaging techniques, two studies employed both neuroelectrical and haemodynamic techniques separately, and one study investigated cerebral neurobiology. Conclusions: The limited available evidence regarding supraspinal mechanisms of SCS does not allow us to develop any conclusive theories. However, the studies included appear to show an inhibitory effect of SCS on somatosensory evoked potentials, as well as identifying the thalamus and anterior cingulate cortex as potential mediators of the pain experience. The lack of substantial evidence in this area highlights the need for large-scale controlled studies of this kind.