Timing of motor cortical stimulation during planar robotic training differentially impacts neuroplasticity in older adults.

PubMed

Massie, Crystal L; Kantak, Shailesh S; Narayanan, Priya; Wittenberg, George F

2015-05-01

The objective was to determine how stimulation timing applied during reaching influenced neuroplasticity related to practice. Older adult participants were studied to increase relevance for stroke rehabilitation and aging. Sixteen participants completed 3 sessions of a reaching intervention with 480 planar robotic movement trials. Sub-threshold, single-pulse transcranial magnetic stimulations (TMS) were delivered during the late reaction time (LRT) period, when muscle activity exceeded a threshold (EMG-triggered), or randomly. Assessments included motor evoked potentials (MEP), amplitude, and direction of supra-threshold TMS-evoked movements and were calculated as change scores from baseline. The direction of TMS-evoked movements significantly changed after reaching practice (p<0.05), but was not significantly different between conditions. Movement amplitude changes were significantly different between conditions (p<0.05), with significant increases following the LRT and random conditions. MEP for elbow extensors and flexors, and the shoulder muscle that opposed the practice movement were significantly different between conditions with positive changes following LRT, negative changes following EMG-triggered, and no changes following the random condition. Motor performance including movement time and peak velocity significantly improved following the training but did not differ between conditions. The responsiveness of the motor cortex to stimulation was affected positively by stimulation during the late motor response period and negatively during the early movement period, when stimulation was combined with robotic reach practice. The sensitivity of the activated motor cortex to additional stimulation is highly dynamic. Copyright © 2015. Published by Elsevier Ireland Ltd.

21 CFR 882.1880 - Evoked response mechanical stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Evoked response mechanical stimulator. 882.1880... mechanical stimulator. (a) Identification. An evoked response mechanical stimulator is a device used to produce a mechanical stimulus or a series of mechanical stimuli for the purpose of measuring a patient's...

21 CFR 882.1870 - Evoked response electrical stimulator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Evoked response electrical stimulator. 882.1870... electrical stimulator. (a) Identification. An evoked response electrical stimulator is a device used to apply an electrical stimulus to a patient by means of skin electrodes for the purpose of measuring the...

21 CFR 882.1870 - Evoked response electrical stimulator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Evoked response electrical stimulator. 882.1870... electrical stimulator. (a) Identification. An evoked response electrical stimulator is a device used to apply an electrical stimulus to a patient by means of skin electrodes for the purpose of measuring the...

21 CFR 882.1870 - Evoked response electrical stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Evoked response electrical stimulator. 882.1870... electrical stimulator. (a) Identification. An evoked response electrical stimulator is a device used to apply an electrical stimulus to a patient by means of skin electrodes for the purpose of measuring the...

21 CFR 882.1870 - Evoked response electrical stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Evoked response electrical stimulator. 882.1870... electrical stimulator. (a) Identification. An evoked response electrical stimulator is a device used to apply an electrical stimulus to a patient by means of skin electrodes for the purpose of measuring the...

Spatial dynamics of action potentials estimated by dendritic Ca(2+) signals in insect projection neurons.

PubMed

Ogawa, Hiroto; Mitani, Ruriko

2015-11-13

The spatial dynamics of action potentials, including their propagation and the location of spike initiation zone (SIZ), are crucial for the computation of a single neuron. Compared with mammalian central neurons, the spike dynamics of invertebrate neurons remain relatively unknown. Thus, we examined the spike dynamics based on single spike-induced Ca(2+) signals in the dendrites of cricket mechanosensory projection neurons, known as giant interneurons (GIs). The Ca(2+) transients induced by a synaptically evoked single spike were larger than those induced by an antidromic spike, whereas subthreshold synaptic potentials caused no elevation of Ca(2+). These results indicate that synaptic activity enhances the dendritic Ca(2+) influx through voltage-gated Ca(2+) channels. Stimulation of the presynaptic sensory afferents ipsilateral to the recording site evoked a dendritic spike with higher amplitude than contralateral stimulation, thereby suggesting that alteration of the spike waveform resulted in synaptic enhancement of the dendritic Ca(2+) transients. The SIZ estimated from the spatial distribution of the difference in the Ca(2+) amplitude was distributed throughout the right and left dendritic branches across the primary neurite connecting them in GIs. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrophysiological characterization of the rat trigeminal caudalis (Vc) neurons following intramuscular injection of capsaicin

PubMed Central

Chun, Yang H; Ro, Jin Y

2009-01-01

Extracellular single unit recording experiments were performed to examine response characteristics of wide dynamic range neurons in the Vc that receive masseter afferent input in Sprague Dawley rats. Capsaicin, or its vehicle, was directly administered into the masseter muscle and changes in resting discharge, responses to mechanical stimulation on the cutaneous receptive field and the electrical threshold for masseter nerve stimulation were assessed. Intramuscular capsaicin induced significant increase in the background discharge and mechanical hypersensitivity to the cutaneous stimulation and lowered the threshold masseter nerve stimulation evoked responses in the majority of neurons. The capsaicin-induced increase in evoked responses, but not the resting discharge, was partially attenuated when the muscle was pretreated with a mGluR antagonist. The present study suggests that injury or inflammation in the masseter muscle induce generalized hyperexcitability of central trigeminal neurons and that the blockade of peripherally localized mGluR5 can effectively attenuate muscular hypersensitivity. PMID:19818833

Analysis of Spontaneous and Nerve-Evoked Calcium Transients in Intact Extraocular Muscles in Vitro

PubMed Central

Feng, Cheng-Yuan; Hennig, Grant W.; Corrigan, Robert D.; Smith, Terence K.; von Bartheld, Christopher S.

2012-01-01

Extraocular muscles (EOMs) have unique calcium handling properties, yet little is known about the dynamics of calcium events underlying ultrafast and tonic contractions in myofibers of intact EOMs. Superior oblique EOMs of juvenile chickens were dissected with their nerve attached, maintained in oxygenated Krebs buffer, and loaded with fluo-4. Spontaneous and nerve stimulation-evoked calcium transients were recorded and, following calcium imaging, some EOMs were double-labeled with rhodamine-conjugated alpha-bungarotoxin (rhBTX) to identify EOM myofiber types. EOMs showed two main types of spontaneous calcium transients, one slow type (calcium waves with 1/2max duration of 2–12 s, velocity of 25–50 μm/s) and two fast “flash-like” types (Type 1, 30–90 ms; Type 2, 90–150 ms 1/2max duration). Single pulse nerve stimulation evoked fast calcium transients identical to the fast (Type 1) calcium transients. Calcium waves were accompanied by a local myofiber contraction that followed the calcium transient wavefront. The magnitude of calcium-wave induced myofiber contraction far exceeded those of movement induced by nerve stimulation and associated fast calcium transients. Tetrodotoxin eliminated nerve-evoked transients, but not spontaneous transients. Alpha-bungarotoxin eliminated both spontaneous and nerve-evoked fast calcium transients, but not calcium waves, and caffeine increased wave activity. Calcium waves were observed in myofibers lacking spontaneous or evoked fast transients, suggestive of multiply-innervated myofibers, and this was confirmed by double-labeling with rhBTX. We propose that the abundant spontaneous calcium transients and calcium waves with localized contractions that do not depend on innervation may contribute to intrinsic generation of tonic functions of EOMs. PMID:22579493

Effect of peripherally and cortically evoked swallows on jaw reflex responses in anesthetized rabbits.

PubMed

Suzuki, Taku; Yoshihara, Midori; Sakai, Shogo; Tsuji, Kojun; Nagoya, Kouta; Magara, Jin; Tsujimura, Takanori; Inoue, Makoto

2018-05-03

This study aimed to investigate whether the jaw-opening (JOR) and jaw-closing reflexes (JCR) are modulated during not only peripherally, but also centrally, evoked swallowing. Experiments were carried out on 24 adult male Japanese white rabbits. JORs were evoked by trigeminal stimulation at 1 Hz for 30 sec. In the middle 10 sec, either the superior laryngeal nerve (SLN) or cortical swallowing area (Cx) was simultaneously stimulated to evoke swallowing. The peak-to-peak JOR amplitude was reduced during the middle and late 10-sec periods (i.e., during and after SLN or Cx stimulation), and the reduction was dependent on the current intensity of SLN/Cx stimulation: greater SLN/Cx stimulus current resulted in greater JOR inhibition. The reduction rate was significantly greater during Cx stimulation than during SLN stimulation. The amplitude returned to baseline 2 min after 10-sec SLN/Cx stimulation. The effect of co-stimulation of SLN and Cx was significantly greater than that of SLN stimulation alone. There were no significant differences in any parameters of the JCR between conditions. These results clearly showed that JOR responses were significantly suppressed, not only during peripherally evoked swallowing but also during centrally evoked swallowing, and that the inhibitory effect is likely to be larger during centrally compared with peripherally evoked swallowing. The functional implications of these results are discussed. Copyright © 2018. Published by Elsevier B.V.

Peripheral optogenetic stimulation induces whisker movement and sensory perception in head-fixed mice.

PubMed

Park, Sunmee; Bandi, Akhil; Lee, Christian R; Margolis, David J

2016-06-08

We discovered that optical stimulation of the mystacial pad in Emx1-Cre;Ai27D transgenic mice induces whisker movements due to activation of ChR2 expressed in muscles controlling retraction and protraction. Using high-speed videography in anesthetized mice, we characterize the amplitude of whisker protractions evoked by varying the intensity, duration, and frequency of optogenetic stimulation. Recordings from primary somatosensory cortex (S1) in anesthetized mice indicated that optogenetic whisker pad stimulation evokes robust yet longer latency responses than mechanical whisker stimulation. In head-fixed mice trained to report optogenetic whisker pad stimulation, psychometric curves showed similar dependence on stimulus duration as evoked whisker movements and S1 activity. Furthermore, optogenetic stimulation of S1 in expert mice was sufficient to substitute for peripheral stimulation. We conclude that whisker protractions evoked by optogenetic activation of whisker pad muscles results in cortical activity and sensory perception, consistent with the coding of evoked whisker movements by reafferent sensory input.

Coordination of eye and head components of movements evoked by stimulation of the paramedian pontine reticular formation.

PubMed

Gandhi, Neeraj J; Barton, Ellen J; Sparks, David L

2008-07-01

Constant frequency microstimulation of the paramedian pontine reticular formation (PPRF) in head-restrained monkeys evokes a constant velocity eye movement. Since the PPRF receives significant projections from structures that control coordinated eye-head movements, we asked whether stimulation of the pontine reticular formation in the head-unrestrained animal generates a combined eye-head movement or only an eye movement. Microstimulation of most sites yielded a constant-velocity gaze shift executed as a coordinated eye-head movement, although eye-only movements were evoked from some sites. The eye and head contributions to the stimulation-evoked movements varied across stimulation sites and were drastically different from the lawful relationship observed for visually-guided gaze shifts. These results indicate that the microstimulation activated elements that issued movement commands to the extraocular and, for most sites, neck motoneurons. In addition, the stimulation-evoked changes in gaze were similar in the head-restrained and head-unrestrained conditions despite the assortment of eye and head contributions, suggesting that the vestibulo-ocular reflex (VOR) gain must be near unity during the coordinated eye-head movements evoked by stimulation of the PPRF. These findings contrast the attenuation of VOR gain associated with visually-guided gaze shifts and suggest that the vestibulo-ocular pathway processes volitional and PPRF stimulation-evoked gaze shifts differently.

Gender differences in binaural speech-evoked auditory brainstem response: are they clinically significant?

PubMed

Jalaei, Bahram; Azmi, Mohd Hafiz Afifi Mohd; Zakaria, Mohd Normani

2018-05-17

Binaurally evoked auditory evoked potentials have good diagnostic values when testing subjects with central auditory deficits. The literature on speech-evoked auditory brainstem response evoked by binaural stimulation is in fact limited. Gender disparities in speech-evoked auditory brainstem response results have been consistently noted but the magnitude of gender difference has not been reported. The present study aimed to compare the magnitude of gender difference in speech-evoked auditory brainstem response results between monaural and binaural stimulations. A total of 34 healthy Asian adults aged 19-30 years participated in this comparative study. Eighteen of them were females (mean age=23.6±2.3 years) and the remaining sixteen were males (mean age=22.0±2.3 years). For each subject, speech-evoked auditory brainstem response was recorded with the synthesized syllable /da/ presented monaurally and binaurally. While latencies were not affected (p>0.05), the binaural stimulation produced statistically higher speech-evoked auditory brainstem response amplitudes than the monaural stimulation (p<0.05). As revealed by large effect sizes (d>0.80), substantive gender differences were noted in most of speech-evoked auditory brainstem response peaks for both stimulation modes. The magnitude of gender difference between the two stimulation modes revealed some distinct patterns. Based on these clinically significant results, gender-specific normative data are highly recommended when using speech-evoked auditory brainstem response for clinical and future applications. The preliminary normative data provided in the present study can serve as the reference for future studies on this test among Asian adults. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

PubMed

Gordon, K A; Papsin, B C; Harrison, R V

2007-08-01

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

Measurements of evoked electroencephalograph by transcranial magnetic stimulation applied to motor cortex and posterior parietal cortex

NASA Astrophysics Data System (ADS)

Iwahashi, Masakuni; Koyama, Yohei; Hyodo, Akira; Hayami, Takehito; Ueno, Shoogo; Iramina, Keiji

2009-04-01

To investigate the functional connectivity, the evoked potentials by stimulating at the motor cortex, the posterior parietal cortex, and the cerebellum by transcranial magnetic stimulation (TMS) were measured. It is difficult to measure the evoked electroencephalograph (EEG) by the magnetic stimulation because of the large artifact induced by the magnetic pulse. We used an EEG measurement system with sample-and-hold circuit and an independent component analysis to eliminate the electromagnetic interaction emitted from TMS. It was possible to measure EEG signals from all electrodes over the head within 10 ms after applying the TMS. When the motor area was stimulated by TMS, the spread of evoked electrical activity to the contralateral hemisphere was observed at 20 ms after stimulation. However, when the posterior parietal cortex was stimulated, the evoked electrical activity to the contralateral hemisphere was not observed. When the cerebellum was stimulated, the cortical activity propagated from the stimulated point to the frontal area and the contralateral hemisphere at around 20 ms after stimulation. These results suggest that the motor area has a strong interhemispheric connection and the posterior parietal cortex has no interhemispheric connection.

Saccade Modulation by Optical and Electrical Stimulation in the Macaque Frontal Eye Field

PubMed Central

Grimaldi, Piercesare; Schweers, Nicole

2013-01-01

Recent studies have demonstrated that strong neural modulations can be evoked with optogenetic stimulation in macaque motor cortex without observing any evoked movements (Han et al., 2009, 2011; Diester et al., 2011). It remains unclear why such perturbations do not generate movements and if conditions exist under which they may evoke movements. In this study, we examine the effects of five optogenetic constructs in the macaque frontal eye field and use electrical microstimulation to assess whether optical perturbation of the local network leads to observable motor changes during optical, electrical, and combined stimulation. We report a significant increase in the probability of evoking saccadic eye movements when low current electrical stimulation is coupled to optical stimulation compared with when electrical stimulation is used alone. Experiments combining channelrhodopsin 2 (ChR2) and electrical stimulation with simultaneous fMRI revealed no discernible fMRI activity at the electrode tip with optical stimulation but strong activity with electrical stimulation. Our findings suggest that stimulation with current ChR2 optogenetic constructs generates subthreshold activity that contributes to the initiation of movements but, in most cases, is not sufficient to evoke a motor response. PMID:24133271

Stable Density and Dynamics of Dendritic Spines of Cortical Neurons Across the Estrous Cycle While Expressing Differential Levels of Sensory-Evoked Plasticity.

PubMed

Alexander, Bailin H; Barnes, Heather M; Trimmer, Emma; Davidson, Andrew M; Ogola, Benard O; Lindsey, Sarah H; Mostany, Ricardo

2018-01-01

Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this in vivo imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE) microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR), survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively), sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%). In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline-not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to sensory-evoked structural plasticity may be dependent on the stage of the cycle. Since dendritic spines are more plastic during proestrus and estrus than during metestrus/diestrus, certain stages of the cycle could be more suitable for forms of memory requiring de novo formation and elimination of spines and other stages for forms of memory where retention and/or repurposing of already existing synaptic connections is more pertinent.

Stable Density and Dynamics of Dendritic Spines of Cortical Neurons Across the Estrous Cycle While Expressing Differential Levels of Sensory-Evoked Plasticity

PubMed Central

Alexander, Bailin H.; Barnes, Heather M.; Trimmer, Emma; Davidson, Andrew M.; Ogola, Benard O.; Lindsey, Sarah H.; Mostany, Ricardo

2018-01-01

Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this in vivo imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE) microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR), survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively), sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%). In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline—not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to sensory-evoked structural plasticity may be dependent on the stage of the cycle. Since dendritic spines are more plastic during proestrus and estrus than during metestrus/diestrus, certain stages of the cycle could be more suitable for forms of memory requiring de novo formation and elimination of spines and other stages for forms of memory where retention and/or repurposing of already existing synaptic connections is more pertinent. PMID:29615867

Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex.

PubMed

Jonas, Jacques; Frismand, Solène; Vignal, Jean-Pierre; Colnat-Coulbois, Sophie; Koessler, Laurent; Vespignani, Hervé; Rossion, Bruno; Maillard, Louis

2014-07-01

Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low-intensity with depth electrodes implanted in the occipito-parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito-parieto-temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Copyright © 2013 Wiley Periodicals, Inc.

Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.

PubMed

Tsuji, Kojun; Tsujimura, Takanori; Magara, Jin; Sakai, Shogo; Nakamura, Yuki; Inoue, Makoto

2015-02-01

The aim of the present study was to investigate the adaptation of the swallowing reflex in terms of reduced swallowing reflex initiation following continuous superior laryngeal nerve stimulation. Forty-four male Sprague Dawley rats were anesthetized with urethane. To identify swallowing, electromyographic activity of the left mylohyoid and thyrohyoid muscles was recorded. To evoke the swallowing response, the superior laryngeal nerve (SLN), recurrent laryngeal nerve, or cortical swallowing area was electrically stimulated. Repetitive swallowing evoked by continuous SLN stimulation was gradually reduced, and this reduction was dependent on the resting time duration between stimulations. Prior SLN stimulation also suppressed subsequent swallowing initiation. The reduction in evoked swallows induced by recurrent laryngeal nerve or cortical swallowing area stimulation was less than that following superior laryngeal nerve stimulation. Decerebration had no effect on the reduction in evoked swallows. Prior subthreshold stimulation reduced subsequent initiation of swallowing, suggesting that there was no relationship between swallowing movement evoked by prior stimulation and the subsequent reduction in swallowing initiation. Overall, these data suggest that reduced sensory afferent nerve firing and/or trans-synaptic responses, as well as part of the brainstem central pattern generator, are involved in adaptation of the swallowing reflex following continuous stimulation of swallow-inducing peripheral nerves and cortical areas. Copyright © 2014 Elsevier Inc. All rights reserved.

Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus.

PubMed

Lentz, Linnea; Zhao, Yan; Kelly, Matthew T; Schindeldecker, William; Goetz, Steven; Nelson, Dwight E; Raike, Robert S

2015-11-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to treat movement disorders, including advanced Parkinson's disease (PD). The pathogenesis of PD and the therapeutic mechanisms of DBS are not well understood. Large animal models are essential for investigating the mechanisms of PD and DBS. The purpose of this study was to develop a novel sheep model of STN DBS and quantify the stimulation-evoked motor behaviors. To do so, a large sample of animals was chronically-implanted with commercial DBS systems. Neuroimaging and histology revealed that the DBS leads were implanted accurately relative to the neurosurgical plan and also precisely relative to the STN. It was also possible to repeatedly conduct controlled evaluations of stimulation-evoked motor behavior in the awake-state. The evoked motor responses depended on the neuroanatomical location of the electrode contact selected for stimulation, as contacts proximal to the STN evoked movements at significantly lower voltages. Tissue stimulation modeling demonstrated that selecting any of the contacts stimulated the STN, whereas selecting the relatively distal contacts often also stimulated thalamus but only the distal-most contact stimulated internal capsule. The types of evoked motor behaviors were specific to the stimulation frequency, as low but not high frequencies consistently evoked movements resembling human tremor or dyskinesia. Electromyography confirmed that the muscle activity underlying the tremor-like movements in the sheep was consistent with human tremor. Overall, this work establishes that the sheep is a viable a large-animal platform for controlled testing of STN DBS with objective motor outcomes. Moreover, the results support the hypothesis that exaggerated low-frequency activity within individual nodes of the motor network can drive symptoms of human movement disorders, including tremor and dyskinesia. Copyright © 2015 Elsevier Inc. All rights reserved.

Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception

NASA Astrophysics Data System (ADS)

Muller, Leah; Rolston, John D.; Fox, Neal P.; Knowlton, Robert; Rao, Vikram R.; Chang, Edward F.

2018-04-01

Objective. Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. Approach. To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. Main results. We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. Significance. Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.

Cortico-cortical evoked potentials for sites of early versus late seizure spread in stereoelectroencephalography.

PubMed

Lega, Bradley; Dionisio, Sasha; Flanigan, Patrick; Bingaman, William; Najm, Imad; Nair, Dileep; Gonzalez-Martinez, Jorge

2015-09-01

Cortico-cortical evoked potentials offer the possibility of understanding connectivity within seizure networks to improve diagnosis and more accurately identify candidates for seizure surgery. We sought to determine if cortico-cortical evoked potentials and post-stimulation oscillatory changes differ for sites of EARLY versus LATE ictal spread. 37 patients undergoing stereoelectroencephalography were tested using a cortico-cortical evoked potential paradigm. All electrodes were classified according to the speed of ictal spread. EARLY spread sites were matched to a LATE spread site equidistant from the onset zone. Root-mean-square was used to quantify evoked responses and post-stimulation gamma band power and coherence were extracted and compared. Sites of EARLY spread exhibited significantly greater evoked responses after stimulation across all patients (t(36)=2.973, p=0.004). Stimulation elicited enhanced gamma band activity at EARLY spread sites (t(36)=2.61, p=0.03, FDR corrected); this gamma band oscillation was highly coherent with the onset zone. Cortico-cortical evoked potentials and post-stimulation changes in gamma band activity differ between sites of EARLY versus LATE ictal spread. The oscillatory changes can help visualize connectivity within the seizure network. Copyright © 2015 Elsevier B.V. All rights reserved.

STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit

PubMed Central

Tian, Meng; Xu, Jian; Lei, Gang; Lombroso, Paul J.; Jackson, Michael F.; MacDonald, John F.

2016-01-01

N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gαq-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A. STEP activation by M1R stimulation requires IP3Rs and can depress NMDA-evoked currents with modest intracellular Ca2+ buffering. Src recruitment by M1R stimulation requires coincident NMDAR activation and can augment NMDA-evoked currents with high intracellular Ca2+ buffering. Our findings suggest that Src and STEP recruitment is contingent on differing intracellular Ca2+ dynamics that dictate whether NMDAR function is augmented or depressed following M1R stimulation. PMID:27857196

Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees.

PubMed

Granata, Giuseppe; Di Iorio, Riccardo; Romanello, Roberto; Iodice, Francesco; Raspopovic, Stanisa; Petrini, Francesco; Strauss, Ivo; Valle, Giacomo; Stieglitz, Thomas; Čvančara, Paul; Andreu, David; Divoux, Jean-Louis; Guiraud, David; Wauters, Loic; Hiairrassary, Arthur; Jensen, Winnie; Micera, Silvestro; Rossini, Paolo Maria

2018-06-01

The aim of the paper is to objectively demonstrate that amputees implanted with intraneural interfaces are truly able to feel a sensation in the phantom hand by recording "phantom" somatosensory evoked potentials from the corresponding brain areas. We implanted four transverse intrafascicular multichannel electrodes, available with percutaneous connections to a multichannel electrical stimulator, in the median and ulnar nerves of two left trans-radial amputees. Two channels of the implants that were able to elicit sensations during intraneural nerve stimulation were chosen, in both patients, for recording somatosensory evoked potentials. We recorded reproducible evoked responses by stimulating the median and the ulnar nerves in both cases. Latencies were in accordance with the arrival of somatosensory information to the primary somatosensory cortex. Our results provide evidence that sensations generated by intraneural stimulation are truly perceived by amputees and located in the phantom hand. Moreover, our results strongly suggest that sensations perceived in different parts of the phantom hand result in different evoked responses. Somatosensory evoked potentials obtained by selective intraneural electrical stimulation in amputee patients are a useful tool to provide an objective demonstration of somatosensory feedback in new generation bidirectional prostheses. Copyright © 2018. Published by Elsevier B.V.

Generalized alternating stimulation: a novel method to reduce stimulus artifact in electrically evoked compound action potentials.

PubMed

Alvarez, Isaac; de la Torre, Angel; Sainz, Manuel; Roldan, Cristina; Schoesser, Hansjoerg; Spitzer, Philipp

2007-09-15

Stimulus artifact is one of the main limitations when considering electrically evoked compound action potential for clinical applications. Alternating stimulation (average of recordings obtained with anodic-cathodic and cathodic-anodic bipolar stimulation pulses) is an effective method to reduce stimulus artifact when evoked potentials are recorded. In this paper we extend the concept of alternating stimulation by combining anodic-cathodic and cathodic-anodic recordings with a weight in general different to 0.5. We also provide an automatic method to obtain an estimation of the optimal weights. Comparison with conventional alternating, triphasic stimulation and masker-probe paradigm shows that the generalized alternating method improves the quality of electrically evoked compound action potential responses.

High frequency oscillations evoked by peripheral magnetic stimulation.

PubMed

Biller, S; Simon, L; Fiedler, P; Strohmeier, D; Haueisen, J

2011-01-01

The analysis of somatosensory evoked potentials (SEP) and / or fields (SEF) is a well-established and important tool for investigating the functioning of the peripheral and central human nervous system. A standard technique to evoke SEPs / SEFs is the stimulation of the median nerve by using a bipolar electrical stimulus. We aim at an alternative stimulation technique enabling stimulation of deep nerve structures while reducing patient stress and error susceptibility. In the current study, we apply a commercial transcranial magnetic stimulation system for peripheral magnetic stimulation of the median nerve. We compare the results of simultaneously recorded EEG signals to prove applicability of our technique to evoke SEPs including low frequency components (LFC) as well as high frequency oscillations (HFO). Therefore, we compare amplitude, latency and time-frequency characteristics of the SEP of 14 healthy volunteers after electric and magnetic stimulation. Both low frequency components and high frequency oscillations were detected. The HFOs were superimposed onto the primary cortical response N20. Statistical analysis revealed significantly lower amplitudes and increased latencies for LFC and HFO components after magnetic stimulation. The differences indicate the inability of magnetic stimulation to elicit supramaximal responses. A psycho-perceptual evaluation showed that magnetic stimulation was less unpleasant for 12 out of the 14 volunteers. In conclusion, we showed that LFC and HFO components related to median nerve stimulation can be evoked by peripheral magnetic stimulation.

Spinal NMDA-receptor dependent amplification of nociceptive transmission to rat primary somatosensory cortex (SI).

PubMed

Kalliomäki, Jarkko; Granmo, Marcus; Schouenborg, Jens

2003-07-01

The role of NMDA mechanisms in spinal pathways mediating acute nociceptive input to the somatosensory cortex is not clear. In this study, the effect of NMDA-antagonists on nociceptive C fibre transmission to the primary somatosensory cortex (SI) was investigated. Cortical field potentials evoked by CO(2)-laser stimulation of the skin were recorded in the halothane/nitrous oxide anaesthetized rat. The SI nociceptive evoked potential (EP) amplitudes were dependent on the frequency of noxious heat stimulation. The amplitudes of SI potentials evoked by CO(2)-laser pulses (duration 15-20 ms, stimulation energy 21-28 mJ/mm(2)) delivered at a frequency of 0.1 Hz were approximately 40% of the amplitudes of potentials evoked by 1.0 Hz stimulation. After intrathecal lumbar application of either of the NMDA-antagonists CPP or MK-801, the amplitudes of nociceptive SI potentials, evoked by 1.0 Hz stimulation of the contralateral hindpaw, were reduced to approximately 40% of controls. By contrast, field potentials evoked by 0.1 Hz stimulation of the hindpaw were unaffected by MK-801. SI potentials evoked by 1.0 Hz stimulation of the contralateral forepaw did not change after lumbar application of CPP or MK-801, indicating that the depression of hindpaw EPs was due to a segmental effect in the spinal cord. It is concluded that spinal NMDA-receptor mechanisms amplify the acute transmission of nociceptive C fiber input to SI in a frequency-dependent way.

Kinetics of fast short-term depression are matched to spike train statistics to reduce noise.

PubMed

Khanbabaie, Reza; Nesse, William H; Longtin, Andre; Maler, Leonard

2010-06-01

Short-term depression (STD) is observed at many synapses of the CNS and is important for diverse computations. We have discovered a form of fast STD (FSTD) in the synaptic responses of pyramidal cells evoked by stimulation of their electrosensory afferent fibers (P-units). The dynamics of the FSTD are matched to the mean and variance of natural P-unit discharge. FSTD exhibits switch-like behavior in that it is immediately activated with stimulus intervals near the mean interspike interval (ISI) of P-units (approximately 5 ms) and recovers immediately after stimulation with the slightly longer intervals (>7.5 ms) that also occur during P-unit natural and evoked discharge patterns. Remarkably, the magnitude of evoked excitatory postsynaptic potentials appear to depend only on the duration of the previous ISI. Our theoretical analysis suggests that FSTD can serve as a mechanism for noise reduction. Because the kinetics of depression are as fast as the natural spike statistics, this role is distinct from previously ascribed functional roles of STD in gain modulation, synchrony detection or as a temporal filter.

Electrical stimulation of rhesus monkey nucleus reticularis gigantocellularis. I. Characteristics of evoked head movements.

PubMed

Quessy, Stephan; Freedman, Edward G

2004-06-01

The nucleus reticularis gigantocellularis (NRG) receives monosynaptic input from the superior colliculus (SC) and projects directly to neck motor neuron pools. Neurons in NRG are well situated to play a critical role in transforming SC signals into head movement commands. A previous study of movements evoked by NRG stimulation in the primate reported a variety of ipsilateral and contralateral head movements with horizontal, vertical and torsional components. In addition to head movements, it was reported that NRG stimulation could evoke movements of the pinnae, face, upper torso, and co-contraction of neck muscles. In this report, the role of the rhesus monkey NRG in head movement control was investigated using electrical stimulation of the rostral portion of the NRG. The goal was to characterize head movements evoked by NRG stimulation, describe the effects of altering stimulation parameters, and assess the relative movements of the eyes and head. Results indicate that electrical stimulation in the rostral portion of the NRG of the primate can consistently evoke ipsilateral head rotations in the horizontal plane. Head movement amplitude and peak velocity depend upon stimulation parameters (primarily frequency and duration of stimulation trains). During stimulation-induced head movements the eyes counter-rotate (presumably a result of the vestibulo-ocular reflex: VOR). At 46 stimulation sites from two subjects the average gain of this counter-rotation was -0.38 (+/-0.18). After the end of the stimulation train the head generally continued to move. During this epoch, after electrical stimulation ceased, VOR gain remained at this reduced level. In addition, VOR gain was similarly low when electrical stimulation was carried out during active fixation of a visual target. These data extend existing descriptions of head movements evoked by electrical stimulation of the NRG, and add to the understanding of the role of this structure in producing head movements.

Functional imaging of glucose-evoked rat islet activities using transient intrinsic optical signals

NASA Astrophysics Data System (ADS)

Yao, Xin-Cheng; Cui, Wan-Xing; Li, Yi-Chao; Zhang, Wei; Lu, Rong-Wen; Thompson, Anthony; Amthor, Franklin; Wang, Xu-Jing

2012-05-01

We demonstrate intrinsic optical signal (IOS) imaging of intact rat islet, which consists of many endocrine cells working together. A near-infrared digital microscope was employed for optical monitoring of islet activities evoked by glucose stimulation. Dynamic NIR images revealed transient IOS responses in the islet activated by low-dose (2.75 mM) and high-dose (5.5 mM) glucose stimuli. Comparative experiments and quantitative analysis indicated that both glucose metabolism and calcium/insulin dynamics might contribute to the observed IOS responses. Further investigation of the IOS imaging technology may provide a high resolution method for ex vivo functional examination of the islet, which is important for advanced study of diabetes associated islet dysfunctions and for improved quality control of donor islets for transplantation.

Optogenetic stimulation of cortex to map evoked whisker movements in awake head-restrained mice.

PubMed

Auffret, Matthieu; Ravano, Veronica L; Rossi, Giulia M C; Hankov, Nicolas; Petersen, Merissa F A; Petersen, Carl C H

2018-01-01

Whisker movements are used by rodents to touch objects in order to extract spatial and textural tactile information about their immediate surroundings. To understand the mechanisms of such active sensorimotor processing it is important to investigate whisker motor control. The activity of neurons in the neocortex affects whisker movements, but many aspects of the organization of cortical whisker motor control remain unknown. Here, we filmed whisker movements evoked by sequential optogenetic stimulation of different locations across the left dorsal sensorimotor cortex of awake head-restrained mice. Whisker movements were evoked by optogenetic stimulation of many regions in the dorsal sensorimotor cortex. Optogenetic stimulation of whisker sensory barrel cortex evoked retraction of the contralateral whisker after a short latency, and a delayed rhythmic protraction of the ipsilateral whisker. Optogenetic stimulation of frontal cortex evoked rhythmic bilateral whisker protraction with a longer latency compared to stimulation of sensory cortex. Compared to frontal cortex stimulation, larger amplitude bilateral rhythmic whisking in a less protracted position was evoked at a similar latency by stimulating a cortical region posterior to Bregma and close to the midline. These data suggest that whisker motor control might be broadly distributed across the dorsal mouse sensorimotor cortex. Future experiments must investigate the complex neuronal circuits connecting specific cell-types in various cortical regions with the whisker motor neurons located in the facial nucleus. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

21 CFR 882.1900 - Evoked response auditory stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Evoked response auditory stimulator. 882.1900 Section 882.1900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1900 Evoked response...

21 CFR 882.1880 - Evoked response mechanical stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Evoked response mechanical stimulator. 882.1880 Section 882.1880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1880 Evoked response...

21 CFR 882.1890 - Evoked response photic stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Evoked response photic stimulator. 882.1890 Section 882.1890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1890 Evoked response...

21 CFR 882.1900 - Evoked response auditory stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Evoked response auditory stimulator. 882.1900 Section 882.1900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1900 Evoked response...

21 CFR 882.1890 - Evoked response photic stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Evoked response photic stimulator. 882.1890 Section 882.1890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1890 Evoked response...

Occlusion of pressor responses to posterior diencephalic stimulation and muscular contraction.

PubMed

Rybicki, K J; Stremel, R W; Iwamoto, G A; Mitchell, J H; Kaufman, M P

1989-02-01

Although neural occlusion has been suggested to occur between the central and reflex mechanisms increasing arterial pressure, evidence consistent with this phenomenon is lacking. To assess the possibility of neural occlusion we recorded, in chloralose-anesthetized cats, the pressor responses to statically contracting the hindlimb muscles and to electrically stimulating histologically confirmed sites in the posterior hypothalamus and subthalamus. We also recorded the pressor responses to topical application of capsaicin onto the intestine and to stimulation of these diencephalic sites. The pressor responses to simultaneous static contraction and diencephalic stimulation were significantly smaller than the algebraic sum of the pressor responses to contraction and diencephalic stimulation evoked separately. Likewise, the pressor responses to simultaneous capsaicin application and diencephalic stimulation were significantly smaller than the algebraic sum of the responses evoked separately. High intensity stimulation of the L7 dorsal root or the diencephalic sites evoked pressor responses similar in magnitude to the algebraic sum of the two responses evoked separately; thus, the inability of the simultaneous maneuvers to evoke pressor responses that summed algebraically was not due to the fact that they caused a maximal effect. Our findings are consistent with the hypothesis that neural occlusion occurs during stimulation of the posterior diencephalon and static muscular contraction.

Analysis of the effect of repeated-pulse transcranial magnetic stimulation at the Guangming point on electroencephalograms.

PubMed

Zhang, Xin; Fu, Lingdi; Geng, Yuehua; Zhai, Xiang; Liu, Yanhua

2014-03-01

Here, we administered repeated-pulse transcranial magnetic stimulation to healthy people at the left Guangming (GB37) and a mock point, and calculated the sample entropy of electroencephalo-gram signals using nonlinear dynamics. Additionally, we compared electroencephalogram sample entropy of signals in response to visual stimulation before, during, and after repeated-pulse tran-scranial magnetic stimulation at the Guangming. Results showed that electroencephalogram sample entropy at left (F3) and right (FP2) frontal electrodes were significantly different depending on where the magnetic stimulation was administered. Additionally, compared with the mock point, electroencephalogram sample entropy was higher after stimulating the Guangming point. When visual stimulation at Guangming was given before repeated-pulse transcranial magnetic stimula-tion, significant differences in sample entropy were found at five electrodes (C3, Cz, C4, P3, T8) in parietal cortex, the central gyrus, and the right temporal region compared with when it was given after repeated-pulse transcranial magnetic stimulation, indicating that repeated-pulse transcranial magnetic stimulation at Guangming can affect visual function. Analysis of electroencephalogram revealed that when visual stimulation preceded repeated pulse transcranial magnetic stimulation, sample entropy values were higher at the C3, C4, and P3 electrodes and lower at the Cz and T8 electrodes than visual stimulation followed preceded repeated pulse transcranial magnetic stimula-tion. The findings indicate that repeated-pulse transcranial magnetic stimulation at the Guangming evokes different patterns of electroencephalogram signals than repeated-pulse transcranial mag-netic stimulation at other nearby points on the body surface, and that repeated-pulse transcranial magnetic stimulation at the Guangming is associated with changes in the complexity of visually evoked electroencephalogram signals in parietal regions, central gyrus, and temporal regions.

Robust Working Memory in an Asynchronously Spiking Neural Network Realized with Neuromorphic VLSI

PubMed Central

Giulioni, Massimiliano; Camilleri, Patrick; Mattia, Maurizio; Dante, Vittorio; Braun, Jochen; Del Giudice, Paolo

2011-01-01

We demonstrate bistable attractor dynamics in a spiking neural network implemented with neuromorphic VLSI hardware. The on-chip network consists of three interacting populations (two excitatory, one inhibitory) of leaky integrate-and-fire (LIF) neurons. One excitatory population is distinguished by strong synaptic self-excitation, which sustains meta-stable states of “high” and “low”-firing activity. Depending on the overall excitability, transitions to the “high” state may be evoked by external stimulation, or may occur spontaneously due to random activity fluctuations. In the former case, the “high” state retains a “working memory” of a stimulus until well after its release. In the latter case, “high” states remain stable for seconds, three orders of magnitude longer than the largest time-scale implemented in the circuitry. Evoked and spontaneous transitions form a continuum and may exhibit a wide range of latencies, depending on the strength of external stimulation and of recurrent synaptic excitation. In addition, we investigated “corrupted” “high” states comprising neurons of both excitatory populations. Within a “basin of attraction,” the network dynamics “corrects” such states and re-establishes the prototypical “high” state. We conclude that, with effective theoretical guidance, full-fledged attractor dynamics can be realized with comparatively small populations of neuromorphic hardware neurons. PMID:22347151

Robust Working Memory in an Asynchronously Spiking Neural Network Realized with Neuromorphic VLSI.

PubMed

Giulioni, Massimiliano; Camilleri, Patrick; Mattia, Maurizio; Dante, Vittorio; Braun, Jochen; Del Giudice, Paolo

2011-01-01

We demonstrate bistable attractor dynamics in a spiking neural network implemented with neuromorphic VLSI hardware. The on-chip network consists of three interacting populations (two excitatory, one inhibitory) of leaky integrate-and-fire (LIF) neurons. One excitatory population is distinguished by strong synaptic self-excitation, which sustains meta-stable states of "high" and "low"-firing activity. Depending on the overall excitability, transitions to the "high" state may be evoked by external stimulation, or may occur spontaneously due to random activity fluctuations. In the former case, the "high" state retains a "working memory" of a stimulus until well after its release. In the latter case, "high" states remain stable for seconds, three orders of magnitude longer than the largest time-scale implemented in the circuitry. Evoked and spontaneous transitions form a continuum and may exhibit a wide range of latencies, depending on the strength of external stimulation and of recurrent synaptic excitation. In addition, we investigated "corrupted" "high" states comprising neurons of both excitatory populations. Within a "basin of attraction," the network dynamics "corrects" such states and re-establishes the prototypical "high" state. We conclude that, with effective theoretical guidance, full-fledged attractor dynamics can be realized with comparatively small populations of neuromorphic hardware neurons.

Explaining how brain stimulation can evoke memories.

PubMed

Jacobs, Joshua; Lega, Bradley; Anderson, Christopher

2012-03-01

An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the "high school-ness" of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.

Monitoring Cortical Excitability during Repetitive Transcranial Magnetic Stimulation in Children with ADHD: A Single-Blind, Sham-Controlled TMS-EEG Study

PubMed Central

Helfrich, Christian; Pierau, Simone S.; Freitag, Christine M.; Roeper, Jochen; Ziemann, Ulf; Bender, Stephan

2012-01-01

Background Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children. Objective TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available. Methods In a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition. Results TMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation. Conclusion The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition. PMID:23185537

Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.

PubMed

Kawaguchi, Jun; Matsuura, Nobuyuki; Kasahara, Masataka; Ichinohe, Tatsuya

2015-02-01

The purpose of this study was to investigate the latency and amplitude of trigeminal somatosensory evoked potentials to clarify how nerve function on the contralateral side is affected after cervical sympathetic block (CSB). Subjects comprised 16 volunteers. For CSB, the tip of a needle was contacted with the transverse process of the sixth cervical vertebra on the right side, and lidocaine was injected. Trigeminal somatosensory evoked potentials were recorded bilaterally from C5/C6 scalp positions. Pupil diameters were also measured. Electrical stimulations were applied to the left-side lower lip, and trigeminal somatosensory evoked potentials waveforms derived from both sides of the scalp were recorded. Then, electrical stimulations were applied to the right-side of the lower lip, and recording was again performed. Recordings were performed at 5, 15, and 30 minutes after CSB. On the CSB side, pupil diameter decreased at 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials at contralateral stimulation showed a prolongation of the latency in both P20 and N25 components on bilateral recording sites 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials' amplitude at contralateral stimulation was smaller than at ipsilateral stimulation 5 minutes after CSB. Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.

Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia.

PubMed

Ewing, Samuel G; Grace, Anthony A

2013-02-01

Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. Copyright © 2012 Elsevier B.V. All rights reserved.

Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia

PubMed Central

Ewing, Samuel G.; Grace, Anthony A.

2012-01-01

Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia, but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. PMID:23269227

Effects of high-level pulse train stimulation on retinal function.

PubMed

Cohen, Ethan D

2009-06-01

We examined how stimulation of the local retina by high-level current pulse trains affected the light-evoked responses of the retinal ganglion cells. The spikes of retinal ganglion cell axons were recorded extracellularly using an in vitro eyecup preparation of the rabbit retina. Epiretinal electrical stimulation was delivered via a 500 microm inner diameter saline-filled, transparent tube positioned over the retinal surface forming the receptive field center. Spot stimuli were presented periodically to the receptive field center during the experiment. Trains of biphasic 1 ms current pulses were delivered to the retina at 50 Hz for 1 min. Pulse train charge densities of 1.3-442 microC/cm(2)/phase were examined. After pulse train stimulation with currents >or=300 microA (133 microC/cm(2)/phase), the ganglion cell's ability to respond to light was depressed and a significant time was required for recovery of the light-evoked response. During train stimulation, the ganglion cell's ability to spike following each current pulse fatigued. The current levels evoking train-evoked depression were suprathreshold to those evoking action potentials. Train-evoked depression was stronger touching the retinal surface, and in some cases impaired ganglion cell function for up to 30 min. This overstimulation could cause a transient refractory period for electrically stimulated perception in the retinal region below the electrode.

Roles of N-methyl-d-aspartate receptors during the sensory stimulation-evoked field potential responses in mouse cerebellar cortical molecular layer.

PubMed

Xu, Yin-Hua; Zhang, Guang-Jian; Zhao, Jing-Tong; Chu, Chun-Ping; Li, Yu-Zi; Qiu, De-Lai

2017-11-01

The functions of N-methyl-d-aspartate receptors (NMDARs) in cerebellar cortex have been widely studied under in vitro condition, but their roles during the sensory stimulation-evoked responses in the cerebellar cortical molecular layer in living animals are currently unclear. We here investigated the roles of NMDARs during the air-puff stimulation on ipsilateral whisker pad-evoked field potential responses in cerebellar cortical molecular layer in urethane-anesthetized mice by electrophysiological recording and pharmacological methods. Our results showed that cerebellar surface administration of NMDA induced a dose-dependent decrease in amplitude of the facial stimulation-evoked inhibitory responses (P1) in the molecular layer, accompanied with decreases in decay time, half-width and area under curve (AUC) of P1. The IC 50 of NMDA induced inhibition in amplitude of P1 was 46.5μM. In addition, application of NMDA induced significant increases in the decay time, half-width and AUC values of the facial stimulation-evoked excitatory responses (N1) in the molecular layer. Application of an NMDAR blocker, D-APV (250μM) abolished the facial stimulation-evoked P1 in the molecular layer. These results suggested that NMDARs play a critical role during the sensory information processing in cerebellar cortical molecular layer in vivo in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Autonomous Optimization of Targeted Stimulation of Neuronal Networks

PubMed Central

Kumar, Sreedhar S.; Wülfing, Jan; Okujeni, Samora; Boedecker, Joschka; Riedmiller, Martin

2016-01-01

Driven by clinical needs and progress in neurotechnology, targeted interaction with neuronal networks is of increasing importance. Yet, the dynamics of interaction between intrinsic ongoing activity in neuronal networks and their response to stimulation is unknown. Nonetheless, electrical stimulation of the brain is increasingly explored as a therapeutic strategy and as a means to artificially inject information into neural circuits. Strategies using regular or event-triggered fixed stimuli discount the influence of ongoing neuronal activity on the stimulation outcome and are therefore not optimal to induce specific responses reliably. Yet, without suitable mechanistic models, it is hardly possible to optimize such interactions, in particular when desired response features are network-dependent and are initially unknown. In this proof-of-principle study, we present an experimental paradigm using reinforcement-learning (RL) to optimize stimulus settings autonomously and evaluate the learned control strategy using phenomenological models. We asked how to (1) capture the interaction of ongoing network activity, electrical stimulation and evoked responses in a quantifiable ‘state’ to formulate a well-posed control problem, (2) find the optimal state for stimulation, and (3) evaluate the quality of the solution found. Electrical stimulation of generic neuronal networks grown from rat cortical tissue in vitro evoked bursts of action potentials (responses). We show that the dynamic interplay of their magnitudes and the probability to be intercepted by spontaneous events defines a trade-off scenario with a network-specific unique optimal latency maximizing stimulus efficacy. An RL controller was set to find this optimum autonomously. Across networks, stimulation efficacy increased in 90% of the sessions after learning and learned latencies strongly agreed with those predicted from open-loop experiments. Our results show that autonomous techniques can exploit quantitative relationships underlying activity-response interaction in biological neuronal networks to choose optimal actions. Simple phenomenological models can be useful to validate the quality of the resulting controllers. PMID:27509295

Autonomous Optimization of Targeted Stimulation of Neuronal Networks.

PubMed

Kumar, Sreedhar S; Wülfing, Jan; Okujeni, Samora; Boedecker, Joschka; Riedmiller, Martin; Egert, Ulrich

2016-08-01

Driven by clinical needs and progress in neurotechnology, targeted interaction with neuronal networks is of increasing importance. Yet, the dynamics of interaction between intrinsic ongoing activity in neuronal networks and their response to stimulation is unknown. Nonetheless, electrical stimulation of the brain is increasingly explored as a therapeutic strategy and as a means to artificially inject information into neural circuits. Strategies using regular or event-triggered fixed stimuli discount the influence of ongoing neuronal activity on the stimulation outcome and are therefore not optimal to induce specific responses reliably. Yet, without suitable mechanistic models, it is hardly possible to optimize such interactions, in particular when desired response features are network-dependent and are initially unknown. In this proof-of-principle study, we present an experimental paradigm using reinforcement-learning (RL) to optimize stimulus settings autonomously and evaluate the learned control strategy using phenomenological models. We asked how to (1) capture the interaction of ongoing network activity, electrical stimulation and evoked responses in a quantifiable 'state' to formulate a well-posed control problem, (2) find the optimal state for stimulation, and (3) evaluate the quality of the solution found. Electrical stimulation of generic neuronal networks grown from rat cortical tissue in vitro evoked bursts of action potentials (responses). We show that the dynamic interplay of their magnitudes and the probability to be intercepted by spontaneous events defines a trade-off scenario with a network-specific unique optimal latency maximizing stimulus efficacy. An RL controller was set to find this optimum autonomously. Across networks, stimulation efficacy increased in 90% of the sessions after learning and learned latencies strongly agreed with those predicted from open-loop experiments. Our results show that autonomous techniques can exploit quantitative relationships underlying activity-response interaction in biological neuronal networks to choose optimal actions. Simple phenomenological models can be useful to validate the quality of the resulting controllers.

Excitation of the corticospinal tract by electromagnetic and electrical stimulation of the scalp in the macaque monkey.

PubMed Central

Edgley, S A; Eyre, J A; Lemon, R N; Miller, S

1990-01-01

1. The responses evoked by non-invasive electromagnetic and surface anodal electrical stimulation of the scalp (scalp stimulation) have been studied in the monkey. Conventional recording and stimulating electrodes, placed in the corticospinal pathway in the hand area of the left motor cortex, left medullary pyramid and the right spinal dorsolateral funiculus (DLF), allowed comparison of the actions of non-invasive stimuli and conventional electrical stimulation. 2. Responses to electromagnetic stimulation (with the coil tangential to the skull) were studied in four anaesthetized monkeys. In each case short-latency descending volleys were recorded in the contralateral DLF at threshold. In two animals later responses were also seen at higher stimulus intensities. Both early and late responses were of corticospinal origin since they could be completely collided by appropriately timed stimulation of the pyramidal tract. The latency of the early response in the DLF indicated that it resulted from direct activation of corticospinal neurones: its latency was the same as the latency of the antidromic action potentials evoked in the motor cortex from the recording site in the DLF. 3. Scalp stimulation, which was also investigated in three of the monkeys, evoked short-latency volleys at threshold and at higher stimulus intensities these were followed by later waves. The short-latency volleys could be collided from the pyramid and, at threshold, had latencies compatible with direct activation of corticospinal neurones. The longer latency volleys were also identified as corticospinal in origin. 4. The latency of the early volley evoked by electromagnetic stimulation remained constant with increasing stimulus intensities. In contrast, with scalp stimulation above threshold the latency of the early volleys decreased considerably, indicating remote activation of the corticospinal pathway below the level of the motor cortex. In two monkeys both collision and latency data suggest activation of the corticospinal pathway as far caudal as the medulla. 5. The majority of fast corticospinal fibres could be excited by scalp stimulation with intensities of 20% of maximum stimulator output. Electromagnetic stimulation at maximum stimulator output elicited a volley of between 70 and 90% of the size of the maximal volley evoked from the pyramidal electrodes. 6. Electromagnetic stimulation was also investigated in one awake monkey during the performance of a precision grip task. Short-latency EMG responses were evoked in hand and forearm muscles. The onsets of these responses were approximately 0.8 ms longer than the responses evoked by electrical stimulation of the pyramid.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 1 PMID:2213581

Magnetic-Stimulation-Related Physiological Artifacts in Hemodynamic Near-Infrared Spectroscopy Signals

PubMed Central

Näsi, Tiina; Mäki, Hanna; Kotilahti, Kalle; Nissilä, Ilkka; Haapalahti, Petri; Ilmoniemi, Risto J.

2011-01-01

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65–0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity. PMID:21887362

Magnetic-stimulation-related physiological artifacts in hemodynamic near-infrared spectroscopy signals.

PubMed

Näsi, Tiina; Mäki, Hanna; Kotilahti, Kalle; Nissilä, Ilkka; Haapalahti, Petri; Ilmoniemi, Risto J

2011-01-01

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65-0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.

Evaluation of focused multipolar stimulation for cochlear implants: a preclinical safety study

NASA Astrophysics Data System (ADS)

Shepherd, Robert K.; Wise, Andrew K.; Enke, Ya Lang; Carter, Paul M.; Fallon, James B.

2017-08-01

Objective. Cochlear implants (CIs) have a limited number of independent stimulation channels due to the highly conductive nature of the fluid-filled cochlea. Attempts to develop highly focused stimulation to improve speech perception in CI users includes the use of simultaneous stimulation via multiple current sources. Focused multipolar (FMP) stimulation is an example of this approach and has been shown to reduce interaction between stimulating channels. However, compared with conventional biphasic current pulses generated from a single current source, FMP is a complex stimulus that includes extended periods of stimulation before charge recovery is achieved, raising questions on whether chronic stimulation with this strategy is safe. The present study evaluated the long-term safety of intracochlear stimulation using FMP in a preclinical animal model of profound deafness. Approach. Six cats were bilaterally implanted with scala tympani electrode arrays two months after deafening, and received continuous unilateral FMP stimulation at levels that evoked a behavioural response for periods of up to 182 d. Electrode impedance, electrically-evoked compound action potentials (ECAPs) and auditory brainstem responses (EABRs) were monitored periodically over the course of the stimulation program from both the stimulated and contralateral control cochleae. On completion of the stimulation program cochleae were examined histologically and the electrode arrays were evaluated for evidence of platinum (Pt) corrosion. Main results. There was no significant difference in electrode impedance between control and chronically stimulated electrodes following long-term FMP stimulation. Moreover, there was no significant difference between ECAP and EABR thresholds evoked from control or stimulated cochleae at either the onset of stimulation or at completion of the stimulation program. Chronic FMP stimulation had no effect on spiral ganglion neuron (SGN) survival when compared with unstimulated control cochleae. Long-term implantation typically evoked a mild foreign body reaction proximal to the electrode array; however stimulated cochleae exhibited a small but statistically significant increase in the tissue response. Finally, there was no evidence of Pt corrosion following long-term FMP stimulation; stimulated electrodes exhibited the same surface features as the unstimulated control electrodes. Significance. Chronic intracochlear FMP stimulation at levels used in the present study did not adversely affect electrically-evoked neural thresholds or SGN survival but evoked a small, benign increase in inflammatory response compared to control ears. Moreover chronic FMP stimulation does not affect the surface of Pt electrodes at suprathreshold stimulus levels. These findings support the safe clinical application of an FMP stimulation strategy.

Interactions between Dorsal and Ventral Root Stimulation on the Generation of Locomotor-Like Activity in the Neonatal Mouse Spinal Cord

PubMed Central

2016-01-01

Abstract We investigated whether dorsal (DR) and ventral root (VR) stimulus trains engage common postsynaptic components to activate the central pattern generator (CPG) for locomotion in the neonatal mouse spinal cord. VR stimulation did not activate the first order interneurons mediating the activation of the locomotor CPG by sacrocaudal afferent stimulation. Simultaneous stimulation of adjacent dorsal or ventral root pairs, subthreshold for evoking locomotor-like activity, did not summate to activate the CPG. This suggests that locomotor-like activity is triggered when a critical class of efferent or afferent axons is stimulated and does not depend on the number of stimulated axons or activated postsynaptic neurons. DR- and VR-evoked episodes exhibited differences in the coupling between VR pairs. In DR-evoked episodes, the coupling between the ipsilateral and contralateral flexor/extensor roots was similar and stronger than the bilateral extensor roots. In VR-evoked episodes, ipsilateral flexor/extensor coupling was stronger than both the contralateral flexor/extensor and the bilateral extensor coupling. For both types of stimulation, the coupling was greatest between the bilateral L1/L2 flexor-dominated roots. This indicates that the recruitment and/or the firing pattern of motoneurons differed in DR and VR-evoked episodes. However, the DR and VR trains do not appear to activate distinct CPGs because trains of DR and VR stimuli at frequencies too low to evoke locomotor-like activity did so when they were interleaved. These results indicate that the excitatory actions of VR stimulation converge onto the CPG through an unknown pathway that is not captured by current models of the locomotor CPG. PMID:27419215

The release of labelled acetylcholine and choline from cerebral cortical slices stimulated electrically

PubMed Central

Richardson, I.W.; Szerb, J.C.

1974-01-01

1 In order to establish the origin of the increased efflux of radioactivity caused by electrical stimulation of cerebral cortical slices which had been incubated with [3H]-choline, labelled choline and acetylcholine (ACh) collected by superfusion were separated by gold precipitation. 2 In the presence of physostigmine electrical stimulation (1 Hz, 10 min) increased the release of only [3H]-ACh which was greatly enhanced by the addition of atropine. 3 Continuous stimulation in the presence of physostigmine resulted in an evoked release of [3H]-ACh which declined asymptotically. This evoked release appeared to follow first-order kinetics with a rate constant which remained stable over the course of prolonged stimulation. 4 The rate constant for the evoked release of [3H]-ACh with 1 Hz stimulation was three times greater in the presence of physostigmine and atropine than in the presence of physostigmine alone, while the size of the store from which [3H]-ACh was released was nearly identical under these two conditions. 5 In the absence of physostigmine and atropine, stimulation caused the appearance of only [3H]-choline in the samples. 6 Reduction of [3H]-ACh stores before the application of physostigmine resulted in a reduced evoked release of total radioactivity, both in the absence or presence of physostigmine and atropine, and decreased the evoked release of [3H]-ACh without affecting the release of [3H]-choline. 7 Results suggest that electrical stimulation of cortical slices which had been incubated with [3H]-choline causes the release of only [3H]-ACh, both in the presence or absence of an anticholinesterase. The evoked increase in the efflux of total radioactivity is therefore a good measure of the release of [3H]-ACh. PMID:4455326

[A Case of Left Vertebral Artery Aneurysm Showing Evoked Potentials on Bilateral Electrode by the Left Vagus Nerve Stimulation to Electromyographic Tracheal Tube].

PubMed

Kadoya, Tatsuo; Uehara, Hirofumi; Yamamoto, Toshinori; Shiraishi, Munehiro; Kinoshita, Yuki; Joyashiki, Takeshi; Enokida, Kengo

2016-02-01

Previously, we reported a case of brainstem cavernous hemangioma showing false positive responses to electromyographic tracheal tube (EMG tube). We concluded that the cause was spontaneous respiration accompanied by vocal cord movement. We report a case of left vertebral artery aneurysm showing evoked potentials on bilateral electrodes by the left vagus nerve stimulation to EMG tube. An 82-year-old woman underwent clipping of a left unruptured vertebral artery-posterior inferior cerebellar artery aneurysm. General anesthesia was induced with remifentanil, propofol and suxamethonium, and was maintained with oxygen, air, remifentanil and propofol. We monitored somatosensory evoked potentials, motor evoked potentials, and electromyogram of the vocal cord. When the manipulation reached brainstem and the instrument touched the left vagus nerve, evoked potentials appeared on bilateral electrodes. EMG tube is equipped with two electrodes on both sides. We concluded that the left vagus nerve stimulation generated evoked potentials of the left laryngeal muscles, and they were simultaneously detected as potential difference between two electrodes on both sides. EMG tube is used to identify the vagus nerve. However, it is necessary to bear in mind that each vagus nerve stimulation inevitably generates evoked potentials on bilateral electrodes.

Characterization of Motor and Somatosensory Evoked Potentials in the Yucatan Micropig Using Transcranial and Epidural Stimulation.

PubMed

Benavides, Francisco D; Santamaria, Andrea J; Bodoukhin, Nikita; Guada, Luis G; Solano, Juan P; Guest, James D

2017-09-15

Yucatan micropigs have brain and spinal cord dimensions similar to humans and are useful for certain spinal cord injury (SCI) translational studies. Micropigs are readily trained in behavioral tasks, allowing consistent testing of locomotor loss and recovery. However, there has been little description of their motor and sensory pathway neurophysiology. We established methods to assess motor and sensory cortical evoked potentials in the anesthetized, uninjured state. We also evaluated epidurally evoked motor and sensory stimuli from the T6 and T9 levels, spanning the intended contusion injury epicenter. Response detection frequency, mean latency and amplitude values, and variability of evoked potentials were determined. Somatosensory evoked potentials were reliable and best detected during stimulation of peripheral nerve and epidural stimulation by referencing the lateral cortex to midline Fz. The most reliable hindlimb motor evoked potential (MEP) occurred in tibialis anterior. We found MEPs in forelimb muscles in response to thoracic epidural stimulation likely generated from propriospinal pathways. Cranially stimulated MEPs were easier to evoke in the upper limbs than in the hindlimbs. Autopsy studies revealed substantial variations in cortical morphology between animals. This electrophysiological study establishes that neurophysiological measures can be reliably obtained in micropigs in a time frame compatible with other experimental procedures, such as SCI and transplantation. It underscores the need to better understand the motor control pathways, including the corticospinal tract, to determine which therapeutics are suitable for testing in the pig model.

Brain stem stimulation and the acetylcholine-evoked inhibition of neurones in the feline nucleus reticularis thalami

PubMed Central

Dingledine, Raymond; Kelly, J. S.

1977-01-01

1. In cats anaesthetized with halothane and nitrous oxide, the responses to iontophoretically applied acetylcholine (ACh) and to high-frequency stimulation of the mid-brain reticular formation (MRF) were tested on spontaneously active neurones in the nucleus reticularis thalami and underlying ventrobasal complex. 2. The initial response to MRF stimulation of 90% of the ACh-inhibited neurones found in the region of the dorsolateral nucleus reticularis was an inhibition. Conversely, the initial response of 82% of the ACh-excited neurones in the ventrobasal complex was an excitation. Neurones in the rostral pole of the nucleus reticularis were inhibited by both ACh and RMF stimulation. 3. The mean latency (and s.e. of mean) for the MRF-evoked inhibition was 13·7 ± 3·2 ms (n = 42) and that for the MRF-evoked excitation, 44.1 ± 4.2 ms (n = 35). 4. The ACh-evoked inhibitions were blocked by iontophoretic atropine, in doses that did not block amino acid-evoked inhibition. In twenty-four ACh-inhibited neurones the effect of iontophoretic atropine was tested on MRF-evoked inhibition. In all twenty-four neurones atropine had no effect on the early phase of MRF-evoked inhibition but weakly antagonized the late phase of inhibition in nine of fourteen neurones. 5. Interspike-interval histograms showed that the firing pattern of neurones in the nucleus reticularis was characterized by periods of prolonged, high-frequency bursting. Both the ACh-evoked inhibitions and the late phase of MRF-evoked inhibitions were accompanied by an increased burst activity. In contrast, iontophoretic atropine tended to suppress burst activity. 6. The possibility is discussed that electrical stimulation of the MRF activates an inhibitory cholinergic projection to the nucleus reticularis. Since neurones of the nucleus reticularis have been shown to inhibit thalamic relay cells, activation of this inhibitory pathway may play a role in MRF-evoked facilitation of thalamo-cortical relay transmission and the associated electrocortical desynchronization. PMID:915830

Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury.

PubMed

Bennett, D J; Sanelli, L; Cooke, C L; Harvey, P J; Gorassini, M A

2004-05-01

Following chronic sacral spinal cord transection in rats the affected tail muscles exhibit marked spasticity, with characteristic long-lasting tail spasms evoked by mild stimulation. The purpose of the present paper was to characterize the long-lasting reflex seen in tail muscles in response to electrical stimulation of the tail nerves in the awake spastic rat, including its development with time and relation to spasticity. Before and after sacral spinal transection, surface electrodes were placed on the tail for electrical stimulation of the caudal nerve trunk (mixed nerve) and for recording EMG from segmental tail muscles. In normal and acute spinal rats caudal nerve trunk stimulation evoked little or no EMG reflex. By 2 wk after injury, the same stimulation evoked long-lasting reflexes that were 1) very low threshold, 2) evoked from rest without prior EMG activity, 3) of polysynaptic latency with >6 ms central delay, 4) about 2 s long, and 5) enhanced by repeated stimulation (windup). These reflexes produced powerful whole tail contractions (spasms) and developed gradually over the weeks after the injury (< or =52 wk tested), in close parallel to the development of spasticity. Pure low-threshold cutaneous stimulation, from electrical stimulation of the tip of the tail, also evoked long-lasting spastic reflexes, not seen in acute spinal or normal rats. In acute spinal rats a strong C-fiber stimulation of the tip of the tail (20 x T) could evoke a weak EMG response lasting about 1 s. Interestingly, when this C-fiber stimulation was used as a conditioning stimulation to depolarize the motoneuron pool in acute spinal rats, a subsequent low-threshold stimulation of the caudal nerve trunk evoked a 300-500 ms long reflex, similar to the onset of the long-lasting reflex in chronic spinal rats. A similar conditioned reflex was not seen in normal rats. Thus there is an unusually long low-threshold polysynaptic input to the motoneurons (pEPSP) that is normally inhibited by descending control. This pEPSP is released from inhibition immediately after injury but does not produce a long-lasting reflex because of a lack of motoneuron excitability. With chronic injury the motoneuron excitability is increased markedly, and the pEPSP then triggers sustained motoneuron discharges associated with long-lasting reflexes and muscle spasms.

The cortical spatiotemporal correlate of otolith stimulation: Vestibular evoked potentials by body translations.

PubMed

Ertl, M; Moser, M; Boegle, R; Conrad, J; Zu Eulenburg, P; Dieterich, M

2017-07-15

The vestibular organ senses linear and rotational acceleration of the head during active and passive motion. These signals are necessary for bipedal locomotion, navigation, the coordination of eye and head movements in 3D space. The temporal dynamics of vestibular processing in cortical structures have hardly been studied in humans, let alone with natural stimulation. The aim was to investigate the cortical vestibular network related to natural otolith stimulation using a hexapod motion platform. We conducted two experiments, 1. to estimate the sources of the vestibular evoked potentials (VestEPs) by means of distributed source localization (n=49), and 2. to reveal modulations of the VestEPs through the underlying acceleration intensity (n=24). For both experiments subjects were accelerated along the main axis (left/right, up/down, fore/aft) while the EEG was recorded. We were able to identify five VestEPs (P1, N1, P2, N2, P3) with latencies between 38 and 461 ms as well as an evoked beta-band response peaking with a latency of 68 ms in all subjects and for all acceleration directions. Source localization gave the cingulate sulcus visual (CSv) area and the opercular-insular region as the main origin of the evoked potentials. No lateralization effects due to handedness could be observed. In the second experiment, area CSv was shown to be integral in the processing of acceleration intensities as sensed by the otolith organs, hinting at its potential role in ego-motion detection. These robust VestEPs could be used to investigate the mechanisms of inter-regional interaction in the natural context of vestibular processing and multisensory integration. Copyright © 2017 Elsevier Inc. All rights reserved.

Computational Modeling of Neurotransmitter Release Evoked by Electrical Stimulation: Nonlinear Approaches to Predicting Stimulation-Evoked Dopamine Release.

PubMed

Trevathan, James K; Yousefi, Ali; Park, Hyung Ook; Bartoletta, John J; Ludwig, Kip A; Lee, Kendall H; Lujan, J Luis

2017-02-15

Neurochemical changes evoked by electrical stimulation of the nervous system have been linked to both therapeutic and undesired effects of neuromodulation therapies used to treat obsessive-compulsive disorder, depression, epilepsy, Parkinson's disease, stroke, hypertension, tinnitus, and many other indications. In fact, interest in better understanding the role of neurochemical signaling in neuromodulation therapies has been a focus of recent government- and industry-sponsored programs whose ultimate goal is to usher in an era of personalized medicine by creating neuromodulation therapies that respond to real-time changes in patient status. A key element to achieving these precision therapeutic interventions is the development of mathematical modeling approaches capable of describing the nonlinear transfer function between neuromodulation parameters and evoked neurochemical changes. Here, we propose two computational modeling frameworks, based on artificial neural networks (ANNs) and Volterra kernels, that can characterize the input/output transfer functions of stimulation-evoked neurochemical release. We evaluate the ability of these modeling frameworks to characterize subject-specific neurochemical kinetics by accurately describing stimulation-evoked dopamine release across rodent (R 2 = 0.83 Volterra kernel, R 2 = 0.86 ANN), swine (R 2 = 0.90 Volterra kernel, R 2 = 0.93 ANN), and non-human primate (R 2 = 0.98 Volterra kernel, R 2 = 0.96 ANN) models of brain stimulation. Ultimately, these models will not only improve understanding of neurochemical signaling in healthy and diseased brains but also facilitate the development of neuromodulation strategies capable of controlling neurochemical release via closed-loop strategies.

Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia.

PubMed

Zittel, S; Helmich, R C; Demiralay, C; Münchau, A; Bäumer, T

2015-08-01

Previous studies indicated that sensorimotor integration and plasticity of the sensorimotor system are impaired in dystonia patients. We investigated motor evoked potential amplitudes and short latency afferent inhibition to examine corticospinal excitability and cortical sensorimotor integration, before and after inhibitory 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex in patients with cervical dystonia (n = 12). Motor evoked potentials were recorded from the right first dorsal interosseous muscle after application of unconditioned transcranial magnetic test stimuli and after previous conditioning electrical stimulation of the right index finger at short interstimulus intervals of 25, 30 and 40 ms. Results were compared to a group of healthy age-matched controls. At baseline, motor evoked potential amplitudes did not differ between groups. Short latency afferent inhibition was reduced in cervical dystonia patients compared to healthy controls. Inhibitory 1 Hz sensory cortex repetitive transcranial magnetic stimulation but not motor cortex repetitive transcranial magnetic stimulation increased motor evoked potential amplitudes in cervical dystonia patients. Additionally, both 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex normalized short latency afferent inhibition in these patients. In healthy subjects, sensory repetitive transcranial magnetic stimulation had no influence on motor evoked potential amplitudes and short latency afferent inhibition. Plasticity of sensorimotor circuits is altered in cervical dystonia patients.

Head position modulates optokinetic nystagmus

PubMed Central

Ferraresi, A.; Botti, F. M.; Panichi, R.; Barmack, N. H.

2011-01-01

Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior → anterior (P → A) direction, slow phase eye velocity (SPEV) increased by 3.5–5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A → P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, “open loop.” Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during “closed loop” HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement. PMID:21735244

Head position modulates optokinetic nystagmus.

PubMed

Pettorossi, V E; Ferraresi, A; Botti, F M; Panichi, R; Barmack, N H

2011-08-01

Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior → anterior (P → A) direction, slow phase eye velocity (SPEV) increased by 3.5-5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A → P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, "open loop." Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during "closed loop" HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement.

Anatomical origin of déjà vu and vivid 'memories' in human temporal lobe epilepsy.

PubMed

Bancaud, J; Brunet-Bourgin, F; Chauvel, P; Halgren, E

1994-02-01

Jackson (Brain 1898; 21: 580-90) observed that seizures arising in the medial temporal lobe may result in a 'dreamy state', consisting of vivid memory-like hallucinations, and/or the sense of having previously lived through exactly the same situation (déjà vu). Penfield demonstrated that the dreamy state can sometimes be evoked by electrical stimulation of the lateral temporal neocortex, especially the superior temporal gyrus. Halgren et al. (Brain 1978; 101: 83-117) showed that the dreamy state can be evoked by stimulation of the hippocampal formation and amygdala and Gloor (Brain 1990; 113: 1673-94) has suggested that it is evoked by lateral stimulation only when the resulting after-discharge spreads medially. In order to resolve the relative importance of these areas, we considered the mental phenomena observed in epileptic patients with electrodes stereotaxically implanted into different brain areas for seizure localization prior to surgical treatment. Sixteen patients, all with seizures involving the temporal lobe, experienced the dreamy state either as a result of spontaneous seizures (nine dreamy states in six patients), or due to electrical stimulation (43 in 14) or to chemical activation (five in three). Déjà vu and hallucinations of scenes were often evoked by different stimulations of the same electrode in the same patient. As Jackson had also observed, the dreamy state could occur alone but was often associated with epigastric phenomena and fear, and followed by loss of contact and oro-alimentary automatisms, and then by simple gestural automatisms, all characteristic of partial seizures beginning in the medial temporal lobe. Furthermore, as also emphasized by Jackson, the dreamy state was seldom associated with sensory illusions. Stimulation of either the neocortex (15 occurrences), anterior hippocampus (17) or amygdala (10) could evoke a dreamy state. However, since fewer hippocampal and amygdala leads were stimulated than temporal neocortical, the proportion of medial temporal electrodes where dreamy states could be evoked was much higher than in the neocortex. Most responsive lateral temporal sites were located in the superior temporal gyrus, rather than the middle temporal gyrus which was significantly less responsive. In 85% of dreamy states evoked by medial temporal lobe stimulation, the discharge spread to the temporal neocortex; and in 53% of dreamy states evoked by lateral temporal stimulation, the discharge spread medially. Considering all dreamy states, the amygdala was involved (as the stimulated structure, or as the site of ictal- or after-discharge) in 73% of cases, the anterior hippocampus in 83% and the temporal neocortex in 88%.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrolyte and protein secretion by the perfused rabbit mandibular gland stimulated with acetylcholine or catecholamines

PubMed Central

Case, R. M.; Conigrave, A. D.; Novak, I.; Young, J. A.

1980-01-01

1. A method is described for the isolation and vascular perfusion in vitro of the mandibular gland of the rabbit. The perfusate is a physiological salt solution containing glucose as the only metabolic substrate. 2. During perfusion with solutions containing acetylcholine, the gland secretes vigorously at a rate and in a manner similar to that seen in vivo. Although the gland becomes oedematous during perfusion, the extent of this oedema appears to have no influence on secretory ability: the perfused glands were capable of functioning for at least 4 h, and often for more than 6 h. 3. Acetylcholine evoked a small secretory response at a concentration of 8 × 10-9 mol l-1 and a maximum response at 8 × 10-7 mol l-1. Eserine (2 × 10-5 mol l-1) evoked secretory responses comparable to those evoked by acetylcholine in a concentration of 8 × 10-9 mol l-1. Secretion, whether unstimulated or evoked by acetylcholine or eserine, could be blocked completely by atropine. 4. During prolonged stimulation with acetylcholine, the fluid secretory response declined rapidly over a period of about 15 min from an initial high value to a much lower plateau value. After 3 or more hours of stimulation, the secretory response began once more to decline, this time towards zero. If, before the second period of decline begins, stimulation is interrupted for about 30 min, the gland recovers its initial responsiveness to further stimulation with acetylcholine. 5. The Na, K, Cl and HCO3 concentrations and the osmolality of acetylcholine evoked saliva exhibited flow-dependency similar to that seen in vivo. The concentrations of Na and Cl, but not K and HCO3, increased by about 25 mmol l-1 during periods of prolonged stimulation with acetylcholine even though the salivary secretory rate was constant. The concentrations of K and HCO3, but not Na and Cl, increased progressively as the concentration of infused acetylcholine was increased. 6. Salivary protein secretion increased with increasing concentrations of acetylcholine to a greater extent than did fluid secretion. During continuous stimulation, the rate of protein secretion fell off much faster than the rate of fluid secretion. 7. The β-adrenergic agonist isoproterenol evoked a fluid secretory response only equal to about 5% of that evoked by acetylcholine, but still the response declined during continued stimulation. The electrolyte composition of isoproterenol-evoked saliva was vastly different from that evoked by acetylcholine, being particularly rich in K and HCO3. The isoproterenol-evoked saliva was also extremely rich in protein so that the total protein secretion evoked by isoproterenol was much greater than that evoked by acetylcholine. 8. The α-adrenergic agonist phenylephrine was without stimulatory effect on salivary fluid secretion and caused a reduction in the secretory response to acetylcholine. The drug had little or no effect on the electrolyte content of acetylcholine-evoked saliva and appeared to reduce its protein content. PMID:7381794

Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.

PubMed

Mittleman, Guy; Goldowitz, Daniel; Heck, Detlef H; Blaha, Charles D

2008-07-01

Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 muA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.

Cerebellar Modulation of Frontal Cortex Dopamine Efflux in Mice: Relevance to Autism and Schizophrenia

PubMed Central

MITTLEMAN, GUY; GOLDOWITZ, DANIEL; HECK, DETLEF H.; BLAHA, CHARLES D.

2013-01-01

Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 μA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked pre-frontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders. PMID:18435424

Recording and assessment of evoked potentials with electrode arrays.

PubMed

Miljković, N; Malešević, N; Kojić, V; Bijelić, G; Keller, T; Popović, D B

2015-09-01

In order to optimize procedure for the assessment of evoked potentials and to provide visualization of the flow of action potentials along the motor systems, we introduced array electrodes for stimulation and recording and developed software for the analysis of the recordings. The system uses a stimulator connected to an electrode array for the generation of evoked potentials, an electrode array connected to the amplifier, A/D converter and computer for the recording of evoked potentials, and a dedicated software application. The method has been tested for the assessment of the H-reflex on the triceps surae muscle in six healthy humans. The electrode array with 16 pads was positioned over the posterior aspect of the thigh, while the recording electrode array with 16 pads was positioned over the triceps surae muscle. The stimulator activated all the pads of the stimulation electrode array asynchronously, while the signals were recorded continuously at all the recording sites. The results are topography maps (spatial distribution of evoked potentials) and matrices (spatial visualization of nerve excitability). The software allows the automatic selection of the lowest stimulation intensity to achieve maximal H-reflex amplitude and selection of the recording/stimulation pads according to predefined criteria. The analysis of results shows that the method provides rich information compared with the conventional recording of the H-reflex with regard the spatial distribution.

Generalization of rapidly recurring seizures is suppressed in mice lacking glial cell line-derived neurotrophic factor family receptor alpha2.

PubMed

Nanobashvili, A; Kokaia, Z; Lindvall, O

2003-01-01

Recent experimental evidence indicates that neurotrophic factors play a role in the pathophysiology of epilepsy. The objective of this study was to explore whether signaling through one of the glial cell line-derived neurotrophic factor family receptors, GFRalpha2, influences the severity of kindling-evoked, rapidly recurring seizures and the subsequent development of permanent hyperexcitability. We applied the rapid kindling model to adult mice, using 40 threshold stimulations delivered with 5-min interval in the ventral hippocampus. Generalized seizures were fewer and developed later in response to kindling stimulations in mice lacking GFRalpha2. However, GFRalpha2 gene deletion did not influence the acquisition of the permanent abnormal excitability as assessed 4 weeks later. In situ hybridization revealed marked and dynamic changes of GFRalpha2 mRNA levels in several forebrain areas following the stimulus-evoked seizures. Our findings provide evidence that signaling through the GFRalpha2 receptor contributes to seizure generalization in rapid kindling.

Descending antinociception induced by secondary somatosensory cortex stimulation in experimental neuropathy: role of the medullospinal serotonergic pathway

PubMed Central

Sagalajev, Boriss; Viisanen, Hanna; Wei, Hong

2017-01-01

Stimulation of the secondary somatosensory cortex (S2) has attenuated pain in humans and inflammatory nociception in animals. Here we studied S2 stimulation-induced antinociception and its underlying mechanisms in an experimental animal model of neuropathy induced by spinal nerve ligation (SNL). Effect of S2 stimulation on heat-evoked limb withdrawal latency was assessed in lightly anesthetized rats that were divided into three groups based on prior surgery and monofilament testing before induction of anesthesia: 1) sham-operated group and 2) hypersensitive and 3) nonhypersensitive (mechanically) SNL groups. In a group of hypersensitive SNL animals, a 5-HT1A receptor agonist was microinjected into the rostroventromedial medulla (RVM) to assess whether autoinhibition of serotonergic cell bodies blocks antinociception. Additionally, effect of S2 stimulation on pronociceptive ON-cells and antinociceptive OFF-cells in the RVM or nociceptive spinal wide dynamic range (WDR) neurons were assessed in anesthetized hypersensitive SNL animals. S2 stimulation induced antinociception in hypersensitive but not in nonhypersensitive SNL or sham-operated animals. Antinociception was prevented by a 5-HT1A receptor agonist in the RVM. Antinociception was associated with decreased duration of heat-evoked response in RVM ON-cells. In spinal WDR neurons, heat-evoked discharge was delayed by S2 stimulation, and this antinociceptive effect was prevented by blocking spinal 5-HT1A receptors. The results indicate that S2 stimulation suppresses nociception in SNL animals if SNL is associated with tactile allodynia-like hypersensitivity. In hypersensitive SNL animals, S2 stimulation induces antinociception mediated by medullospinal serotonergic pathways acting on the spinal 5-HT1A receptor, and partly through reduction of the RVM ON-cell discharge. NEW & NOTEWORTHY Stimulation of S2 cortex, but not that of an adjacent cortical area, induced descending heat antinociception in rats with the spinal nerve ligation-induced model of neuropathy. Antinociception was bilateral, and it involved suppression of pronociceptive medullary cells and activation of serotonergic pathways that act on the spinal 5-HT1A receptor. S2 stimulation failed to induce descending antinociceptive effect in sham-operated controls or in nerve-ligated animals that had not developed mechanical hypersensitivity. PMID:28053243

Network activity influences the subthreshold and spiking visual responses of pyramidal neurons in the three-layer turtle cortex.

PubMed

Wright, Nathaniel C; Wessel, Ralf

2017-10-01

A primary goal of systems neuroscience is to understand cortical function, typically by studying spontaneous and stimulus-modulated cortical activity. Mounting evidence suggests a strong and complex relationship exists between the ongoing and stimulus-modulated cortical state. To date, most work in this area has been based on spiking in populations of neurons. While advantageous in many respects, this approach is limited in scope: it records the activity of a minority of neurons and gives no direct indication of the underlying subthreshold dynamics. Membrane potential recordings can fill these gaps in our understanding, but stable recordings are difficult to obtain in vivo. Here, we recorded subthreshold cortical visual responses in the ex vivo turtle eye-attached whole brain preparation, which is ideally suited for such a study. We found that, in the absence of visual stimulation, the network was "synchronous"; neurons displayed network-mediated transitions between hyperpolarized (Down) and depolarized (Up) membrane potential states. The prevalence of these slow-wave transitions varied across turtles and recording sessions. Visual stimulation evoked similar Up states, which were on average larger and less reliable when the ongoing state was more synchronous. Responses were muted when immediately preceded by large, spontaneous Up states. Evoked spiking was sparse, highly variable across trials, and mediated by concerted synaptic inputs that were, in general, only very weakly correlated with inputs to nearby neurons. Together, these results highlight the multiplexed influence of the cortical network on the spontaneous and sensory-evoked activity of individual cortical neurons. NEW & NOTEWORTHY Most studies of cortical activity focus on spikes. Subthreshold membrane potential recordings can provide complementary insight, but stable recordings are difficult to obtain in vivo. Here, we recorded the membrane potentials of cortical neurons during ongoing and visually evoked activity. We observed a strong relationship between network and single-neuron evoked activity spanning multiple temporal scales. The membrane potential perspective of cortical dynamics thus highlights the influence of intrinsic network properties on visual processing. Copyright © 2017 the American Physiological Society.

Artifacts produced during electrical stimulation of the vestibular nerve in cats. [autonomic nervous system components of motion sickness

NASA Technical Reports Server (NTRS)

Tang, P. C.

1973-01-01

Evidence is presented to indicate that evoked potentials in the recurrent laryngeal, the cervical sympathetic, and the phrenic nerve, commonly reported as being elicited by vestibular nerve stimulation, may be due to stimulation of structures other than the vestibular nerve. Experiments carried out in decerebrated cats indicated that stimulation of the petrous bone and not that of the vestibular nerve is responsible for the genesis of evoked potentials in the recurrent laryngeal and the cervical sympathetic nerves. The phrenic response to electrical stimulation applied through bipolar straight electrodes appears to be the result of stimulation of the facial nerve in the facial canal by current spread along the petrous bone, since stimulation of the suspended facial nerve evoked potentials only in the phrenic nerve and not in the recurrent laryngeal nerve. These findings indicate that autonomic components of motion sickness represent the secondary reactions and not the primary responses to vestibular stimulation.

Properties of visual evoked potentials to onset of movement on a television screen.

PubMed

Kubová, Z; Kuba, M; Hubacek, J; Vít, F

1990-08-01

In 80 subjects the dependence of movement-onset visual evoked potentials on some measures of stimulation was examined, and these responses were compared with pattern-reversal visual evoked potentials to verify the effectiveness of pattern movement application for visual evoked potential acquisition. Horizontally moving vertical gratings were generated on a television screen. The typical movement-onset reactions were characterized by one marked negative peak only, with a peak time between 140 and 200 ms. In all subjects the sufficient stimulus duration for acquisition of movement-onset-related visual evoked potentials was 100 ms; in some cases it was only 20 ms. Higher velocity (5.6 degree/s) produced higher amplitudes of movement-onset visual evoked potentials than did the lower velocity (2.8 degrees/s). In 80% of subjects, the more distinct reactions were found in the leads from lateral occipital areas (in 60% from the right hemisphere), with no correlation to handedness of subjects. Unlike pattern-reversal visual evoked potentials, the movement-onset responses tended to be larger to extramacular stimulation (annular target of 5 degrees-9 degrees) than to macular stimulation (circular target of 5 degrees diameter).

Cortico-Cortical interactions between and within three cortical auditory areas specialized for time-domain signal processing

PubMed Central

Tang, Jie; Suga, Nobuo

2009-01-01

In auditory cortex of the mustached bat, the FF (F means frequency modulation), dorsal fringe (DF) and ventral fringe (VF) areas consist of “combination-sensitive” neurons tuned to the pair of an emitted biosonar pulse and its echo with a specific delay (best delay: BD). The DF and VF areas are hierarchically at a higher level than the FF area. Focal electric stimulation of the FF area evokes “centrifugal” BD shifts of DF neurons, i.e., shifts away from the BD of the stimulated FF neurons, whereas stimulation of the DF neurons evokes “centripetal” BD shifts of FF neurons, i.e., shifts toward the BD of the stimulated DF neurons. In our current studies, we found that the feed forward projection from FF neurons evokes centrifugal BD shifts of VF neurons, that the feedback projection from VF neurons evokes centripetal BD shifts of FF neurons, that the contralateral projection from DF neurons evokes centripetal BD shifts of DF neurons, and that the centripetal BD shifts evoked by the DF and VF neurons are 2.5 times larger than the centrifugal BD shifts evoked by the FF neurons. The centrifugal BD shifts shape the selective neural representation of a specific target-distance, whereas the centripetal BD shifts expand the representation of the selected specific target-distance to focus on the processing of the target information at a specific distance. The centrifugal and centripetal BD shifts evoked by the feed forward and feedback projections promote finer analysis of a target at shorter distances. PMID:19494145

Vibrissae-evoked behavior and conditioning before functional ontogeny of the somatosensory vibrissae cortex.

PubMed

Landers, M S; Sullivan, R M

1999-06-15

The following experiments determined that the somatosensory whisker system is functional and capable of experience-dependent behavioral plasticity in the neonate before functional maturation of the somatosensory whisker cortex. First, unilateral whisker stimulation caused increased behavioral activity in both postnatal day (P) 3-4 and P8 pups, whereas stimulation-evoked cortical activity (14C 2-deoxyglucose autoradiography) was detectable only in P8 pups. Second, neonatal rat pups are capable of forming associations between whisker stimulation and a reinforcer. A classical conditioning paradigm (P3-P4) showed that the learning groups (paired whisker stimulation-shock or paired whisker stimulation-warm air stream) exhibited significantly higher behavioral responsiveness to whisker stimulation than controls. Finally, stimulus-evoked somatosensory cortical activity during testing [P8; using 14C 2-deoxyglucose (2-DG) autoradiography] was assessed after somatosensory conditioning from P1-P8. No learning-associated differences in stimulus-evoked cortical activity were detected between learning and nonlearning control groups. Together, these experiments demonstrate that the whisker system is functional in neonates and capable of experience-dependent behavioral plasticity. Furthermore, in contrast to adult somatosensory classical conditioning, these data suggest that the cortex is not required for associative somatosensory learning in neonates.

Pain-related somatosensory evoked potentials and functional brain magnetic resonance in the evaluation of neurologic recovery after cardiac arrest: a case study of three patients.

PubMed

Zanatta, Paolo; Messerotti Benvenuti, Simone; Baldanzi, Fabrizio; Bendini, Matteo; Saccavini, Marsilio; Tamari, Wadih; Palomba, Daniela; Bosco, Enrico

2012-03-31

This case series investigates whether painful electrical stimulation increases the early prognostic value of both somatosensory-evoked potentials and functional magnetic resonance imaging in comatose patients after cardiac arrest. Three single cases with hypoxic-ischemic encephalopathy were considered. A neurophysiological evaluation with an electroencephalogram and somatosensory-evoked potentials during increased electrical stimulation in both median nerves was performed within five days of cardiac arrest. Each patient also underwent a functional magnetic resonance imaging evaluation with the same neurophysiological protocol one month after cardiac arrest. One patient, who completely recovered, showed a middle latency component at a high intensity of stimulation and the activation of all brain areas involved in cerebral pain processing. One patient in a minimally conscious state only showed the cortical somatosensory response and the activation of the primary somatosensory cortex. The last patient, who was in a vegetative state, did not show primary somatosensory evoked potentials; only the activation of subcortical brain areas occurred. These preliminary findings suggest that the pain-related somatosensory evoked potentials performed to increase the prognosis of comatose patients after cardiac arrest are associated with regional brain activity showed by functional magnetic resonance imaging during median nerves electrical stimulation. More importantly, this cases report also suggests that somatosensory evoked potentials and functional magnetic resonance imaging during painful electrical stimulation may be sensitive and complementary methods to predict the neurological outcome in the acute phase of coma. Thus, pain-related somatosensory-evoked potentials may be a reliable and a cost-effective tool for planning the early diagnostic evaluation of comatose patients.

Stimulation-evoked Ca2+ signals in astrocytic processes at hippocampal CA3-CA1 synapses of adult mice are modulated by glutamate and ATP.

PubMed

Tang, Wannan; Szokol, Karolina; Jensen, Vidar; Enger, Rune; Trivedi, Chintan A; Hvalby, Øivind; Helm, P Johannes; Looger, Loren L; Sprengel, Rolf; Nagelhus, Erlend A

2015-02-18

To date, it has been difficult to reveal physiological Ca(2+) events occurring within the fine astrocytic processes of mature animals. The objective of the study was to explore whether neuronal activity evokes astrocytic Ca(2+) signals at glutamatergic synapses of adult mice. We stimulated the Schaffer collateral/commissural fibers in acute hippocampal slices from adult mice transduced with the genetically encoded Ca(2+) indicator GCaMP5E driven by the glial fibrillary acidic protein promoter. Two-photon imaging revealed global stimulation-evoked astrocytic Ca(2+) signals with distinct latencies, rise rates, and amplitudes in fine processes and somata. Specifically, the Ca(2+) signals in the processes were faster and of higher amplitude than those in the somata. A combination of P2 purinergic and group I/II metabotropic glutamate receptor (mGluR) antagonists reduced the amplitude of the Ca(2+) transients by 30-40% in both astrocytic compartments. Blockage of the mGluRs alone only modestly reduced the magnitude of the stimulation-evoked Ca(2+) signals in processes and failed to affect the somatic Ca(2+) response. Local application of group I or I/II mGluR agonists or adenosine triphosphate (ATP) elicited global astrocytic Ca(2+) signals that mimicked the stimulation-evoked astrocytic Ca(2+) responses. We conclude that stimulation-evoked Ca(2+) signals in astrocytic processes at CA3-CA1 synapses of adult mice (1) differ from those in astrocytic somata and (2) are modulated by glutamate and ATP. Copyright © 2015 the authors 0270-6474/15/353016-06$15.00/0.

Intracortical pathways mediate nonlinear fast oscillation (>200 Hz) interactions within rat barrel cortex.

PubMed

Staba, Richard J; Ard, Tyler D; Benison, Alexander M; Barth, Daniel S

2005-05-01

Whisker evoked fast oscillations (FOs; >200 Hz) within the rodent posteromedial barrel subfield are thought to reflect very rapid integration of multiwhisker stimuli, yet the pathways mediating FO interactions remain unclear and may involve interactions within thalamus and/or cortex. In the present study using anesthetized rats, a cortical incision was made between sites representing the stimulated whiskers to determine how intracortical networks contributed to patterns of FOs. With cortex intact, simultaneous stimulation of a pair of whiskers aligned in a row evoked supralinear responses between sites separated by several millimeters. In contrast, stimulation of a nonadjacent pair of whiskers within an arc evoked FOs with no evidence for nonlinear interactions. However, stimulation of an adjacent pair of whiskers in an arc did evoke supralinear responses. After a cortical cut, supralinear interactions associated with FOs within a row were lost. These data indicate a distinct bias for stronger long-range connectivity that extends along barrel rows and that horizontal intracortical pathways exclusively mediate FO-related integration of tactile information.

Real-time monitoring of electrically evoked catecholamine signals in the songbird striatum using in vivo fast-scan cyclic voltammetry.

PubMed

Smith, Amanda R; Garris, Paul A; Casto, Joseph M

2015-01-01

Fast-scan cyclic voltammetry is a powerful technique for monitoring rapid changes in extracellular neurotransmitter levels in the brain. In vivo fast-scan cyclic voltammetry has been used extensively in mammalian models to characterize dopamine signals in both anesthetized and awake preparations, but has yet to be applied to a non-mammalian vertebrate. The goal of this study was to establish in vivo fast-scan cyclic voltammetry in a songbird, the European starling, to facilitate real-time measurements of extracellular catecholamine levels in the avian striatum. In urethane-anesthetized starlings, changes in catecholamine levels were evoked by electrical stimulation of the ventral tegmental area and measured at carbon-fiber microelectrodes positioned in the medial and lateral striata. Catecholamines were elicited by different stimulations, including trains related to phasic dopamine signaling in the rat, and were analyzed to quantify presynaptic mechanisms governing exocytotic release and neuronal uptake. Evoked extracellular catecholamine dynamics, maximal amplitude of the evoked catecholamine signal, and parameters for catecholamine release and uptake did not differ between striatal regions and were similar to those determined for dopamine in the rat dorsomedial striatum under similar conditions. Chemical identification of measured catecholamine by its voltammogram was consistent with the presence of both dopamine and norepinephrine in striatal tissue content. However, the high ratio of dopamine to norepinephrine in tissue content and the greater sensitivity of the carbon-fiber microelectrode to dopamine compared to norepinephrine favored the measurement of dopamine. Thus, converging evidence suggests that dopamine was the predominate analyte of the electrically evoked catecholamine signal measured in the striatum by fast-scan cyclic voltammetry. Overall, comparisons between the characteristics of these evoked signals suggested a similar presynaptic regulation of dopamine in the starling and rat striatum. Fast-scan cyclic voltammetry thus has the potential to be an invaluable tool for investigating the neural underpinnings of behavior in birds. Copyright © 2015 Elsevier B.V. All rights reserved.

Real-time monitoring of electrically evoked catecholamine signals in the songbird striatum using in vivo fast-scan cyclic voltammetry

PubMed Central

Smith, Amanda R.; Garris, Paul A.; Casto, Joseph M.

2015-01-01

Fast-scan cyclic voltammetry is a powerful technique for monitoring rapid changes in extracellular neurotransmitter levels in the brain. In vivo fast-scan cyclic voltammetry has been used extensively in mammalian models to characterize dopamine signals in both anesthetized and awake preparations, but has yet to be applied to a non-mammalian vertebrate. The goal of this study was to establish in vivo fast-scan cyclic voltammetry in a songbird, the European starling, to facilitate real-time measurements of extracellular catecholamine levels in the avian striatum. In urethane-anesthetized starlings, changes in catecholamine levels were evoked by electrical stimulation of the ventral tegmental area and measured at carbon-fiber microelectrodes positioned in the medial and lateral striata. Catecholamines were elicited by different stimulations, including trains related to phasic dopamine signaling in the rat, and were analyzed to quantify presynaptic mechanisms governing exocytotic release and neuronal uptake. Evoked extracellular catecholamine dynamics, maximal amplitude of the evoked catecholamine signal, and parameters for catecholamine release and uptake did not differ between striatal regions and were similar to those determined for dopamine in the rat dorsomedial striatum under similar conditions. Chemical identification of measured catecholamine by its voltammogram was consistent with the presence of both dopamine and norepinephrine in striatal tissue content. However, the high ratio of dopamine to norepinephrine in tissue content and the greater sensitivity of the carbon-fiber microelectrode to dopamine compared to norepinephrine favored the measurement of dopamine. Thus, converging evidence suggests that dopamine was the predominate analyte of the electrically evoked catecholamine signal measured in the striatum by fast-scan cyclic voltammetry. Overall, comparisons between the characteristics of these evoked signals suggested a similar presynaptic regulation of dopamine in the starling and rat striatum. Fast-scan cyclic voltammetry thus has the potential to be an invaluable tool for investigating the neural underpinnings of behavior in birds. PMID:25900708

Recruitment of local inhibitory networks by horizontal connections in layer 2/3 of ferret visual cortex.

PubMed

Tucker, Thomas R; Katz, Lawrence C

2003-01-01

To investigate how neurons in cortical layer 2/3 integrate horizontal inputs arising from widely distributed sites, we combined intracellular recording and voltage-sensitive dye imaging to visualize the spatiotemporal dynamics of neuronal activity evoked by electrical stimulation of multiple sites in visual cortex. Individual stimuli evoked characteristic patterns of optical activity, while delivering stimuli at multiple sites generated interacting patterns in the regions of overlap. We observed that neurons in overlapping regions received convergent horizontal activation that generated nonlinear responses due to the emergence of large inhibitory potentials. The results indicate that co-activation of multiple sets of horizontal connections recruit strong inhibition from local inhibitory networks, causing marked deviations from simple linear integration.

Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials.

PubMed

La Cesa, S; Di Stefano, G; Leone, C; Pepe, A; Galosi, E; Alu, F; Fasolino, A; Cruccu, G; Valeriani, M; Truini, A

2018-01-01

In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system. © 2017 European Pain Federation - EFIC®.

Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon

PubMed Central

Fei, Guijun; Wang, Yu-Zhong; Liu, Sumei; Hu, Hong-Zhen; Wang, Guo-Du; Qu, Mei-Hua; Wang, Xi-Yu; Xia, Yun; Sun, Xiaohong; Bohn, Laura M.; Cooke, Helen J.; Wood, Jackie D.

2009-01-01

Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1–3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1–3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1–3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed (P < 0.001) lubiprostone-evoked Isc. Lubiprostone, in the presence of tetrodotoxin, enhanced carbachol-evoked Isc. The cholinergic component, but not the putative vasoactive intestinal peptide component, of neural responses to electrical field stimulation was enhanced by lubiprostone. Application of any of the prostaglandins, E2, F2, or I2, evoked depolarization of the resting membrane potential in enteric neurons. Unlike the prostaglandins, lubiprostone did not alter the electrical behavior of enteric neurons. Exposure to the histamine H2 receptor agonists increased basal Isc followed by persistent cyclical increases in Isc. Lubiprostone increased the peak amplitude of the dimaprit-evoked cycles. PMID:19179625

Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon.

PubMed

Fei, Guijun; Wang, Yu-Zhong; Liu, Sumei; Hu, Hong-Zhen; Wang, Guo-Du; Qu, Mei-Hua; Wang, Xi-Yu; Xia, Yun; Sun, Xiaohong; Bohn, Laura M; Cooke, Helen J; Wood, Jackie D

2009-04-01

Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1-3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed (P<0.001) lubiprostone-evoked Isc. Lubiprostone, in the presence of tetrodotoxin, enhanced carbachol-evoked Isc. The cholinergic component, but not the putative vasoactive intestinal peptide component, of neural responses to electrical field stimulation was enhanced by lubiprostone. Application of any of the prostaglandins, E2, F2, or I2, evoked depolarization of the resting membrane potential in enteric neurons. Unlike the prostaglandins, lubiprostone did not alter the electrical behavior of enteric neurons. Exposure to the histamine H2 receptor agonists increased basal Isc followed by persistent cyclical increases in Isc. Lubiprostone increased the peak amplitude of the dimaprit-evoked cycles.

A5 region modulation of the cardiorespiratory responses evoked from parabrachial cell bodies in the anaesthetised rat.

PubMed

Dawid Milner, M S; Lara, J P; López de Miguel, M P; López-González, M V; Spyer, K M; González-Barón, S

2003-08-22

We have examined the importance of the A5 region modulating cardiorespiratory responses evoked from the parabrachial complex (PB) in spontaneously breathing rats. Cardiorespiratory changes were analyzed in response to electrical stimulation and glutamate microinjections into the PB (10-20 nl, 1-2 nmol) before and after ipsilateral microinjection of muscimol (50 nl, 0.25 nmol) or lidocaine (50 nl, 0.5 nmol) within the A5 region. Stimulation of medial parabrachial and Kölliker-Fuse nuclei (mPB-KF) evoked a decrease in respiratory rate (P<0.001) with a rise in blood pressure (P<0.001) and heart rate (P<0.05). After muscimol or lidocaine microinjections within the A5 region, the pressor and heart rate responses to mPB-KF stimulation were reduced (P<0.05, both cases). Muscimol within the A5 region altered the respiratory response to glutamate stimulation of mPB-KF, evoking an increase in respiratory rate (P<0.05). Lidocaine abolished the respiratory response to mPB-KF stimulation. Stimulation of the lateral parabrachial nuclei (lPB) caused an increase in respiratory rate (P<0.001) with a rise in blood pressure (P<0.001) and heart rate (P<0.05). Muscimol or lidocaine microinjections within A5 region decreased heart rate (P<0.05) and pressor responses (P<0.05) evoked from lPB. The increase of respiratory rate persisted unchanged. To confirm functional interactions between A5 and PB, extracellular recordings of putative A5 neurones were obtained during PB stimulation. Eighty-three A5 cells were recorded, 35 were activated from the mPB-KF (42%). The results indicate that neurones of the A5 region participate in the cardiorespiratory response evoked from the different regions of the PB complex. The possible mechanisms involved in these interactions are discussed.

Optimization of SSVEP brain responses with application to eight-command Brain-Computer Interface.

PubMed

Bakardjian, Hovagim; Tanaka, Toshihisa; Cichocki, Andrzej

2010-01-18

This study pursues the optimization of the brain responses to small reversing patterns in a Steady-State Visual Evoked Potentials (SSVEP) paradigm, which could be used to maximize the efficiency of applications such as Brain-Computer Interfaces (BCI). We investigated the SSVEP frequency response for 32 frequencies (5-84 Hz), and the time dynamics of the brain response at 8, 14 and 28 Hz, to aid the definition of the optimal neurophysiological parameters and to outline the onset-delay and other limitations of SSVEP stimuli in applications such as our previously described four-command BCI system. Our results showed that the 5.6-15.3 Hz pattern reversal stimulation evoked the strongest responses, peaking at 12 Hz, and exhibiting weaker local maxima at 28 and 42 Hz. After stimulation onset, the long-term SSVEP response was highly non-stationary and the dynamics, including the first peak, was frequency-dependent. The evaluation of the performance of a frequency-optimized eight-command BCI system with dynamic neurofeedback showed a mean success rate of 98%, and a time delay of 3.4s. Robust BCI performance was achieved by all subjects even when using numerous small patterns clustered very close to each other and moving rapidly in 2D space. These results emphasize the need for SSVEP applications to optimize not only the analysis algorithms but also the stimuli in order to maximize the brain responses they rely on. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Oesophageal sensation assessed by electrical stimuli and brain evoked potentials--a new model for visceral nociception.

PubMed Central

Frøbert, O; Arendt-Nielsen, L; Bak, P; Funch-Jensen, P; Bagger, J P

1995-01-01

Sensory thresholds and brain evoked potentials were determined in 12 healthy volunteers using electrical stimulation of the oesophagus 28 and 38 cm from the nares. The peaks of the evoked potentials were designated N for negative deflections and P for positive. Continuous electrical stimulation (40 Hz) at the 38 cm position resembled heartburn (five of 12 subjects) while non-specific ('electrical') sensations were provoked at 28 cm (10 of 12). Thresholds of sensation and of pain were lower at the initial than the second determination, but did not differ with respect to stimulation site. The pain summation threshold to repeated stimuli (2 Hz, 5 stimuli) was determined for the first time in a viscus. This threshold was lower than the pain threshold to single stimuli at 38 cm (p < 0.02). Evoked potential latencies did not change significantly over a six month period while the N1/P2 amplitude was higher at the first measurement (p < 0.05). P1 and N1 latencies were significantly shorter 38 cm (medians 100 and 141 ms) than 28 cm from the nares (102 and 148 ms) (p = 0.04 and p = 0.008). Electrical stimulation of the oesophagus may serve as a human experimental model for visceral pain. Longer evoked potential latencies from the proximal compared with distal stimulations provide new information about the sensory pathways of the oesophagus. PMID:8549932

Specific CA3 neurons decode neural information of dentate granule cells evoked by paired-pulse stimulation in co-cultured networks.

PubMed

Poli, Daniele; DeMarse, Thomas B; Wheeler, Bruce C; Brewer, Gregory J

2017-07-01

CA3 and dentate gyrus (DG) neurons are cultured in two-chamber devices on multi-electrode arrays (MEAs) and connected via micro-tunnels. In order to evoke time-locked activity, paired-pulse stimulation is applied to 22 different sites and repeated 25 times in each well in 5 MEA co-cultures and results compared to CA3-CA3 and DG-DG networks homologous controls. In these hippocampal sub-regions, we focus on the mechanisms underpinning a network's ability to decode the identity of site specific stimulation from analysis of evoked network responses using a support vector machine classifier. Our results indicate that a pool of CA3 neurons is able to reliably decode the identity of DG stimulation site information.

Does navigated transcranial stimulation increase the accuracy of tractography? A prospective clinical trial based on intraoperative motor evoked potential monitoring during deep brain stimulation.

PubMed

Forster, Marie-Therese; Hoecker, Alexander Claudius; Kang, Jun-Suk; Quick, Johanna; Seifert, Volker; Hattingen, Elke; Hilker, Rüdiger; Weise, Lutz Martin

2015-06-01

Tractography based on diffusion tensor imaging has become a popular tool for delineating white matter tracts for neurosurgical procedures. To explore whether navigated transcranial magnetic stimulation (nTMS) might increase the accuracy of fiber tracking. Tractography was performed according to both anatomic delineation of the motor cortex (n = 14) and nTMS results (n = 9). After implantation of the definitive electrode, stimulation via the electrode was performed, defining a stimulation threshold for eliciting motor evoked potentials recorded during deep brain stimulation surgery. Others have shown that of arm and leg muscles. This threshold was correlated with the shortest distance between the active electrode contact and both fiber tracks. Results were evaluated by correlation to motor evoked potential monitoring during deep brain stimulation, a surgical procedure causing hardly any brain shift. Distances to fiber tracks clearly correlated with motor evoked potential thresholds. Tracks based on nTMS had a higher predictive value than tracks based on anatomic motor cortex definition (P < .001 and P = .005, respectively). However, target site, hemisphere, and active electrode contact did not influence this correlation. The implementation of tractography based on nTMS increases the accuracy of fiber tracking. Moreover, this combination of methods has the potential to become a supplemental tool for guiding electrode implantation.

Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus.

PubMed

Verma, Rohit U; Guex, Amélie A; Hancock, Kenneth E; Durakovic, Nedim; McKay, Colette M; Slama, Michaël C C; Brown, M Christian; Lee, Daniel J

2014-04-01

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. Copyright © 2014 Elsevier B.V. All rights reserved.

Auditory Responses to Electric and Infrared Neural Stimulation of the Rat Cochlear Nucleus

PubMed Central

Verma, Rohit; Guex, Amelie A.; Hancock, Kenneth E.; Durakovic, Nedim; McKay, Colette M.; Slama, Michaël C. C.; Brown, M. Christian; Lee, Daniel J.

2014-01-01

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported “optophonic” effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. PMID:24508368

Acetylcholine is released from taste cells, enhancing taste signalling

PubMed Central

Dando, Robin; Roper, Stephen D

2012-01-01

Acetylcholine (ACh), a candidate neurotransmitter that has been implicated in taste buds, elicits calcium mobilization in Receptor (Type II) taste cells. Using RT-PCR analysis and pharmacological interventions, we demonstrate that the muscarinic acetylcholine receptor M3 mediates these actions. Applying ACh enhanced both taste-evoked Ca2+ responses and taste-evoked afferent neurotransmitter (ATP) secretion from taste Receptor cells. Blocking muscarinic receptors depressed taste-evoked responses in Receptor cells, suggesting that ACh is normally released from taste cells during taste stimulation. ACh biosensors confirmed that, indeed, taste Receptor cells secrete acetylcholine during gustatory stimulation. Genetic deletion of muscarinic receptors resulted in significantly diminished ATP secretion from taste buds. The data demonstrate a new role for acetylcholine as a taste bud transmitter. Our results imply specifically that ACh is an autocrine transmitter secreted by taste Receptor cells during gustatory stimulation, enhancing taste-evoked responses and afferent transmitter secretion. PMID:22570381

Innovative neurophysiological methods in itch research: long-latency evoked potentials after electrical and thermal stimulation in patients with atopic dermatitis.

PubMed

Yudina, Marina M; Toropina, Galina G; Lvov, Andrey; Gieler, Uwe

2011-10-01

The aim of this study was to examine the findings of innovative neurophysiological methods of itch research. Short-latency and pain-related somatosensory-evoked potentials after electrical stimulation, as well as long-latency evoked potentials after thermal stimulation were studied in 38 patients with atopic dermatitis (AD) and 26 healthy volunteers. Quantitative Sensory Testing of thermal perception was performed in 22 patients with AD from the main AD group and in 15 healthy volunteers. Brain hyperactivity to electrical stimuli, delayed thermal-evoked potentials and elevated thermal thresholds were revealed in patients with AD compared with healthy controls. The data indicate small nerve fibre dysfunction in patients with AD, which may contribute to the pathogenesis of AD and chronic itch. The study demonstrates objective approaches to assess the function of small nerve fibres in patients with chronic itch.

Identification of Stimulated Sites Using Artificial Neural Networks Based on Transcranial Magnetic Stimulation-Elicited Motor Evoked Potentials and Finger Forces

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Odagaki, Masato; Hiwaki, Osamu

Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) vary in their amplitude from trial to trial. To investigate the functions of motor cortex by TMS, it is necessary to confirm the causal relationship between stimulated sites and variable MEPs. We created artificial neural networks to classify sets of variable MEP signals and finger forces into the corresponding stimulated sites. We conducted TMS at three different positions over M1 and measured MEPs of hand and forearm muscles and forces of the index finger in four subjects. We estimated the sites within motor cortex stimulated by TMS based on cortical columnar structure and nerve excitation properties. Finally, we tried to classify the various MEPs and finger forces into three groups using artificial neural networks. MEPs and finger forces varied from trial to trial, even if the stimulating coil was fixed on the subject's head. Our proposed neural network was able to identify the MEPs and finger forces with the corresponding stimulated sites in M1. We proposed the artificial neural networks to confirm the TMS-stimulated sites using various MEPs and evoked finger forces.

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses

PubMed Central

Mishra, Asht M.; Pal, Ajay; Gupta, Disha

2017-01-01

Key points Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord.The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone.Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal.Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Abstract Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. PMID:28752624

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

PubMed

Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

2017-11-15

Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Sensitivity to microstimulation of somatosensory cortex distributed over multiple electrodes.

PubMed

Kim, Sungshin; Callier, Thierri; Tabot, Gregg A; Tenore, Francesco V; Bensmaia, Sliman J

2015-01-01

Meaningful and repeatable tactile sensations can be evoked by electrically stimulating primary somatosensory cortex. Intracortical microstimulation (ICMS) may thus be a viable approach to restore the sense of touch in individuals who have lost it, for example tetraplegic patients. One of the potential limitations of this approach, however, is that high levels of current can damage the neuronal tissue if the resulting current densities are too high. The limited range of safe ICMS amplitudes thus limits the dynamic range of ICMS-evoked sensations. One way to get around this limitation would be to distribute the ICMS over multiple electrodes in the hopes of intensifying the resulting percept without increasing the current density experienced by the neuronal tissue. Here, we test whether stimulating through multiple electrodes is a viable solution to increase the dynamic range of ICMS-elicited sensations without increasing the peak current density. To this end, we compare the ability of non-human primates to detect ICMS delivered through one vs. multiple electrodes. We also compare their ability to discriminate pulse trains differing in amplitude when these are delivered through one or more electrodes. We find that increasing the number of electrodes through which ICMS is delivered only has a marginal effect on detectability or discriminability despite the fact that 2-4 times more current is delivered overall. Furthermore, the impact of multielectrode stimulation (or lack thereof) is found whether pulses are delivered synchronously or asynchronously, whether the leading phase of the pulses is cathodic or anodic, and regardless of the spatial configuration of the electrode groups.

Electrophysiological studies of the nervous system

NASA Technical Reports Server (NTRS)

Galambos, R.

1972-01-01

The electrophysiology of the nervous system is studied using cats and human subjects. Data cover effects of chlorolose on evoked potential, the evoked resistance shift that accompanies evoked potentials, and the relationship of eye movements to potentials aroused by visual stimulation.

Effect of combined opioid receptor and α2-adrenoceptor blockade on anxiety and electrically evoked startle responses.

PubMed

Vo, Lechi; Drummond, Peter D

2017-06-01

The R3 component of the electrically evoked blink reflex may form part of a startle reaction. Acoustic startle responses are augmented by yohimbine, an α 2 -adrenoceptor antagonist that blocks α 2 -autoreceptors, and are potentiated by opioid receptor blockade. To investigate these influences on electrically evoked startle responses, 16 mg yohimbine, with (16 participants) or without 50 mg naltrexone (23 participants), was administered in separate double-blind placebo-controlled cross-over experiments. In each experiment, R3 (a probable component of the startle response) was examined before and after high-frequency electrical stimulation of the forearm, a procedure that initiates inhibitory pain controls. Anxiety and somatic symptoms were greater after yohimbine than placebo, and were potentiated by naltrexone. Pain ratings for the electrically evoked startle stimuli decreased after high-frequency electrical stimulation in the placebo session but remained stable after drug administration. Yohimbine with naltrexone, but not yohimbine alone, also blocked an inhibitory effect of high-frequency electrical stimulation on electrically evoked sharp sensations and R3. Together, the findings suggest that adding naltrexone to yohimbine potentiated anxiety and blocked inhibitory influences of high-frequency electrical stimulation on electrically evoked sensations and startle responses. Thus, opioid peptides could reduce activity in nociceptive and startle-reflex pathways, or inhibit crosstalk between these pathways. Failure of this inhibitory opioid influence might be important in chronically painful conditions that are aggravated by startle stimuli.

Cutaneous stimulation of discrete regions of the sole during locomotion produces “sensory steering” of the foot

PubMed Central

2014-01-01

Background While the neural and mechanical effects of whole nerve cutaneous stimulation on human locomotion have been previously studied, there is less information about effects evoked by activation of discrete skin regions on the sole of the foot. Electrical stimulation of discrete foot regions evokes position-modulated patterns of cutaneous reflexes in muscles acting at the ankle during standing but data during walking are lacking. Here, non-noxious electrical stimulation was delivered to five discrete locations on the sole of the foot (heel, and medial and lateral sites on the midfoot and forefoot) during treadmill walking. EMG activity from muscles acting at the hip, knee and ankle were recorded along with movement at these three joints. Additionally, 3 force sensing resistors measuring continuous force changes were placed at the heel, and the medial and lateral aspects of the right foot sole. All data were sorted based on stimulus occurrence in twelve step-cycle phases, before being averaged together within a phase for subsequent analysis. Methods Non-noxious electrical stimulation was delivered to five discrete locations on the sole of the foot (heel, and medial and lateral sites on the midfoot and forefoot) during treadmill walking. EMG activity from muscles acting at the hip, knee and ankle were recorded along with movement at these three joints. Additionally, 3 force sensing resistors measuring continuous force changes were placed at the heel, and the medial and lateral aspects of the right foot sole. All data were sorted based on stimulus occurrence in twelve step-cycle phases, before being averaged together within a phase for subsequent analysis. Results The results demonstrate statistically significant dynamic changes in reflex amplitudes, kinematics and foot sole pressures that are site-specific and phase-dependent. The general trends demonstrate responses producing decreased underfoot pressure at the site of stimulation. Conclusions The responses to stimulation of discrete locations on the foot sole evoke a kind of “sensory steering” that may promote balance and maintenance of locomotion through the modulation of limb loading and foot placement. These results have implications for using sensory stimulation as a therapeutic modality during gait retraining (e.g. after stroke) as well as for footwear design and implementation of foot sole contact surfaces during gait. PMID:25202452

A dynamic model of the eye nystagmus response to high magnetic fields.

PubMed

Glover, Paul M; Li, Yan; Antunes, Andre; Mian, Omar S; Day, Brian L

2014-02-07

It was recently shown that high magnetic fields evoke nystagmus in human subjects with functioning vestibular systems. The proposed mechanism involves interaction between ionic currents in the endolymph of the vestibular labyrinth and the static magnetic field. This results in a Lorentz force that causes endolymph flow to deflect the cupulae of the semi-circular canals to evoke a vestibular-ocular reflex (VOR). This should be analogous to stimulation by angular acceleration or caloric irrigation. We made measurements of nystagmus slow-phase velocities in healthy adults experiencing variable magnetic field profiles of up to 7 T while supine on a bed that could be moved smoothly into the bore of an MRI machine. The horizontal slow-phase velocity data were reliably modelled by a linear transfer function incorporating a low-pass term and a high-pass adaptation term. The adaptation time constant was estimated at 39.3 s from long exposure trials. When constrained to this value, the low-pass time constant was estimated at 13.6 ± 3.6 s (to 95% confidence) from both short and long exposure trials. This confidence interval overlaps with values obtained previously using angular acceleration and caloric stimulation. Hence it is compatible with endolymph flow causing a cupular deflection and therefore supports the hypothesis that the Lorentz force is a likely transduction mechanism of the magnetic field-evoked VOR.

Induction of panic attack by stimulation of the ventromedial hypothalamus.

PubMed

Wilent, W Bryan; Oh, Michael Y; Buetefisch, Cathrin M; Bailes, Julian E; Cantella, Diane; Angle, Cindy; Whiting, Donald M

2010-06-01

Panic attacks are sudden debilitating attacks of intense distress often accompanied by physical symptoms such as shortness of breath and heart palpitations. Numerous brain regions, hormones, and neurotransmitter systems are putatively involved, but the etiology and neurocircuitry of panic attacks is far from established. One particular brain region of interest is the ventromedial hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH has been shown to evoke an emotional "panic attack-like" escape behavior, and in humans, stimulation targeting nuclei just posterior or anterior to the VMH has reportedly induced panic attacks. The authors report findings obtained in an awake patient undergoing bilateral implantation of deep brain stimulation electrodes into the hypothalamus that strongly implicates the VMH as being critically involved in the genesis of panic attacks. First, as the stimulating electrode progressed deeper into the VMH, the intensity of stimulation required to evoke an attack systematically decreased; second, while stimulation of the VMH in either hemisphere evoked panic, stimulation that appeared to be in the center of the VMH was more potent. Thus, this evidence supports the role of the VMH in the induction of panic attacks purported by animal studies.

Response of anterior parietal cortex to cutaneous flutter versus vibration.

PubMed

Tommerdahl, M; Delemos, K A; Whitsel, B L; Favorov, O V; Metz, C B

1999-07-01

The response of anesthetized squirrel monkey anterior parietal (SI) cortex to 25 or 200 Hz sinusoidal vertical skin displacement stimulation was studied using the method of optical intrinsic signal (OIS) imaging. Twenty-five-Hertz ("flutter") stimulation of a discrete skin site on either the hindlimb or forelimb for 3-30 s evoked a prominent increase in absorbance within cytoarchitectonic areas 3b and 1 in the contralateral hemisphere. This response was confined to those area 3b/1 regions occupied by neurons with a receptive field (RF) that includes the stimulated skin site. In contrast, same-site 200-Hz stimulation ("vibration") for 3-30 s evoked a decrease in absorbance in a much larger territory (most frequently involving areas 3b, 1, and area 3a, but in some subjects area 2 as well) than the region that undergoes an increase in absorbance during 25-Hz flutter stimulation. The increase in absorbance evoked by 25-Hz flutter developed quickly and remained relatively constant for as long as stimulation continued (stimulus duration never exceeded 30 s). At 1-3 s after stimulus onset, the response to 200-Hz stimulation, like the response to 25-Hz flutter, consisted of a localized increase in absorbance limited to the topographically appropriate region of area 3b and/or area 1. With continuing 200-Hz stimulation, however, the early response declined, and by 4-6 s after stimulus onset, it was replaced by a prominent and spatially extensive decrease in absorbance. The spike train responses of single quickly adapting (QA) neurons were recorded extracellularly during microelectrode penetrations that traverse the optically responding regions of areas 3b and 1. Onset of either 25- or 200-Hz stimulation at a site within the cutaneous RF of a QA neuron was accompanied by a substantial increase in mean spike firing rate. With continued 200-Hz stimulation, however, QA neuron mean firing rate declined rapidly (typically within 0.5-1.0 s) to a level below that recorded at the same time after onset of same-site 25-Hz stimulation. For some neurons, the mean firing rate after the initial 0.5-1 s of an exposure to 200-Hz stimulation of the RF decreased to a level below the level of background ("spontaneous") activity. The decline in both the stimulus-evoked increases in absorbance in areas 3b/1 and spike discharge activity of area 3b/1 neurons within only a few seconds of the onset of 200-Hz skin stimulation raised the possibility that the predominant effect of continuous 200-Hz stimulation for >3 s is inhibition of area 3b/1 QA neurons. This possibility was evaluated at the neuronal population level by comparing the intrinsic signal evoked in areas 3b/1 by 25-Hz skin stimulation to the intrinsic signal evoked by a same-site skin stimulus containing both 25- and 200-Hz sinusoidal components (a "complex waveform stimulus"). Such experiments revealed that the increase in absorbance evoked in areas 3b/1 by a stimulus having both 25- and 200-Hz components was substantially smaller (especially at times >3 s after stimulus onset) than the increase in absorbance evoked by "pure" 25-Hz stimulation of the same skin site. It is concluded that within a brief time (within 1-3 s) after stimulus onset, 200-Hz skin stimulation elicits a powerful inhibitory action on area 3b/1 QA neurons. The findings appear generally consistent with the suggestion that the activity of neurons in cortical regions other than areas 3b and 1 play the leading role in the processing of high-frequency (>/=200 Hz) vibrotactile stimuli.

Nonlinear Analyses of Elicited Modal, Raised, and Pressed Rabbit Phonation

PubMed Central

Awan, Shaheen N.; Novaleski, Carolyn K.; Rousseau, Bernard

2014-01-01

Objectives/Hypothesis The purpose of this study was to use nonlinear dynamic analysis methods such as phase space portraits and correlation dimension (D2) as well as descriptive spectrographic analyses to characterize acoustic signals produced during evoked rabbit phonation. Methods Seventeen New Zealand white breeder rabbits were used to perform the study. A Grass S-88 stimulator (SA Instrumentation, Encinitas, CA) and constant current isolation unit (Grass Telefactor, model PSIU6; West Warwick, RI) were used to provide electrical stimulation to laryngeal musculature, and transglottal airflow rate and stimulation current (mA) were manipulated to elicit modal, raised intensity, and pressed phonations. Central 1 second portions of the most stable portion of the acoustic waveform for modal, raised intensity, and pressed phonations were edited, and then analyzed via phase space portraits, Poincaré sections, and the estimation of the correlation dimension (D2). In an attempt to limit the effects of the highly variable and nonstationary characteristics of some of the signals being analyzed, D2 analysis was also performed on the most stable central 200 ms portion of the acoustic waveform. Descriptive analysis of each phonation was also conducted using sound spectrograms. Results Results showed that the complexity of phonation and the subsequent acoustic waveform is increased as transglottal airflow rate and degree of glottal adduction is manipulated in the evoked rabbit phonation model. In particular, phonatory complexity, as quantified via correlation dimension analyses and demonstrated via spectrographic characteristics, increases from “modal” (i.e., phonation elicited at just above the phonation threshold pressure) to raised intensity (phonation elicited by increasing transglottal airflow rate) to pressed (phonation elicited by increasing the stimulation current delivered to the larynx). Variations in a single dynamic dimension (airflow rate or adductory force) resulted in significantly increased productions of nonlinear phenomenon, including bifurcations from periodicity to regions of subharmonic content, F0 and harmonic jumps, and evidence of periodicity within aperiodic regions (“chaos”). Conclusions The evoked rabbit phonation model described in this study allows for the elicitation of various types of phonations under controlled conditions and therefore, has the potential to provide insight regarding important variables that may elicit examples of nonlinear phenomena such as subharmonics and deterministic chaos. PMID:24836360

Otolithic influences on extraocular and intraocular muscles

NASA Technical Reports Server (NTRS)

Gernandt, B. E.

1973-01-01

Selective stimulation of utricular gravireceptors leads to gross activation of the bulbar reticular formation where a strong interaction with evoked spino-bulbo-spinal reflex activity occurs. The utricular neurons encountered by microelectrodes in the lateral vestibular nuclei show four types of elicited activity; two of these display an increased firing rate, and two exhibit pronounced inhibitory effects. Application of a stimulus of long duration and constant intensity to the utricle has shown that rapid adaptation of the peripheral receptors is a prominent feature. The effects of selective utricular stimulation upon eye movements, as recorded by the corneoretinal potential method, have been studied in experiments on cats and monkeys and it can be firmly stated that prolonged stimulation of the utricle can evoke strong primary nystagmus, followed by a secondary nystagmus at the cessation of stimulation. The action of utricular stimulation on ocular reflexes has been examined further, with particular attention to evoked pupillary reactions in both cats and monkeys: constriction during the fast phase of the brisk conjugate eye movement, and dilatation during the flow phase.

Noxious stimuli do not determine reflex cardiorespiratory effects in anesthetized rabbits.

PubMed

Raimondi, G; Legramante, J M; Iellamo, F; Frisardi, G; Cassarino, S; Peruzzi, G

1996-12-01

The main purpose of this study is to examine whether the stimulation of an exclusively pain-sensing receptive field (dental pulp) could determine cardiorespiratory effects in animals in which the cortical integration of the peripheral information is abolished by deep anesthesia. In 15 anesthetized (alpha-chloralose and urethan) rabbits, low (3-Hz)- and high-frequency (100-Hz) electrical dental pulp stimulation was performed. Because this stimulation caused dynamic and static reflex contractions of the digastric muscles leading to jaw opening jaw-opening reflex (JOR); an indirect sign of algoceptive fiber activation], experimentally induced direct dynamic and static contractions of the digastric muscle were also performed. The low- and high-frequency stimulation of the dental pulp determined cardiovascular [systolic arterial pressure (SAP): -21.7 +/- 4.6 and 10.8 +/- 4.7 mmHg, respectively] and respiratory [pulmonary ventilation (VE): 145.1 +/- 44.9 and 109.3 +/- 28.4 ml/min, respectively] reflex responses similar to those observed during experimentally induced dynamic (SAP: -17.5 +/- 4.2 mmHg; VE: 228.0 +/- 58.5 ml/min) and static (SAP: 5.8 +/- 1.5 mmHg; VE: 148.0 +/- 75.3 ml/min) muscular contractions. The elimination of digastric muscular contraction (JOR) obtained by muscular paralysis did away with the cardiovascular changes induced by dental pulp stimulation, the effectiveness of which in stimulating dental pulp receptors has been shown by recording trigeminal-evoked potentials in six additional rabbits. The main conclusion was that, in deeply anesthetized animals, an algesic stimulus is unable to determine cardiorespiratory effects, which appear to be exclusively linked to the stimulation of ergoreceptors induced by muscular contraction.

Skinfold thickness affects the isometric knee extension torque evoked by Neuromuscular Electrical Stimulation.

PubMed

Medeiros, Flávia V A; Vieira, Amilton; Carregaro, Rodrigo L; Bottaro, Martim; Maffiuletti, Nicola A; Durigan, João L Q

2015-01-01

Subcutaneous adipose tissue may influence the transmission of electrical stimuli through to the skin, thus affecting both evoked torque and comfort perception associated with neuromuscular electrical stimulation (NMES). This could seriously affect the effectiveness of NMES for either rehabilitation or sports purposes. To investigate the effects of skinfold thickness (SFT) on maximal NMES current intensity, NMES-evoked torque, and NMES-induced discomfort. First, we compared NMES current intensity, NMES-induced discomfort, and NMES-evoked torque between two subgroups of subjects with thicker (n=10; 20.7 mm) vs. thinner (n=10; 29.4 mm) SFT. Second, we correlated SFT to NMES current intensity, NMES-induced discomfort, and NMES-evoked knee extension torque in 20 healthy women. The NMES-evoked torque was normalized to the maximal voluntary contraction (MVC) torque. The discomfort induced by NMES was assessed with a visual analog scale (VAS). NMES-evoked torque was 27.5% lower in subjects with thicker SFT (p=0.01) while maximal current intensity was 24.2% lower in subjects with thinner SFT (p=0.01). A positive correlation was found between current intensity and SFT (r=0.540, p=0.017). A negative correlation was found between NMES-evoked torque and SFT (r=-0.563, p=0.012). No significant correlation was observed between discomfort scores and SFT (rs=0.15, p=0.53). These results suggest that the amount of subcutaneous adipose tissue (as reflected by skinfold thickness) affected NMES current intensity and NMES-evoked torque, but had no effect on discomfort perception. Our findings may help physical therapists to better understand the impact of SFT on NMES and to design more rational stimulation strategies.

Adaptive changes in the neuromagnetic response of the primary and association somatosensory areas following repetitive tactile hand stimulation in humans

PubMed Central

Popescu, Anda; Barlow, Steven; Venkatesan, Lalit; Wang, Jingyan; Popescu, Mihai

2014-01-01

Cortical adaptation in the primary somatosensory cortex (SI) has been probed using different stimulation modalities and recording techniques, in both human and animal studies. In contrast, considerably less knowledge has been gained about the adaptation profiles in other areas of the cortical somatosensory network. Using magnetoencephalography, we examined the patterns of short-term adaptation for evoked responses in SI and somatosensory association areas during tactile stimulation applied to the glabrous skin of the right hand. Cutaneous stimuli were delivered as trains of serial pulses with a constant frequency of 2 Hz and 4 Hz in separate runs, and a constant inter-train interval of 5 s. The unilateral stimuli elicited transient responses to the serial pulses in the train, with several response components that were separated by Independent Component Analysis. Subsequent neuromagnetic source reconstruction identified regional generators in the contralateral SI and somatosensory association areas in the posterior parietal cortex (PPC). Activity in the bilateral secondary somatosensory cortex (i.e. SII/PV) was also identified, although less consistently across subjects. The dynamics of the evoked activity in each area and the frequency-dependent adaptation effects were assessed from the changes in the relative amplitude of serial responses in each train. We show that the adaptation profiles in SI and PPC can be quantitatively characterized from neuromagnetic recordings using tactile stimulation, with the sensitivity to repetitive stimulation increasing from SI to PPC. A similar approach for SII/PV has proven less straightforward, potentially due to the selective nature of these areas to respond predominantly to certain stimuli. PMID:22331631

Recovery of TES-MEPs during surgical decompression of the spine: a case series of eight patients.

PubMed

Visser, Jetze; Verra, Wiebe C; Kuijlen, Jos M; Horsting, Philip P; Journée, Henricus L

2014-12-01

This study aimed to illustrate the recovery of transcranial electrical stimulation motor evoked potentials during surgical decompression of the spinal cord in patients with impaired motor function preoperatively. Specific attention was paid to the duration of neurologic symptoms before surgery and the postoperative clinical recovery. A case series of eight patients was selected from a cohort of 74 patients that underwent spine surgery. The selected patients initially had low or absent transcranial electrical stimulation motor evoked potentials followed by a significant increase after surgical decompression of the spinal cord. A significant intraoperative increase in amplitude of motor evoked potentials was detected after decompression of the spinal cord or cauda equina in patients suffering from spinal canal stenosis (n = 2), extradural meningioma (n = 3), or a herniated nucleus polposus (n = 3). This was related to an enhanced neurologic outcome only if patients (n = 6) had a short onset (less than ½ year) of neurologic impairment before surgery. In patients with a short onset of neurologic impairment because of compression of the spinal cord or caudal fibers, an intraoperative recovery of transcranial electrical stimulation motor evoked potentials can indicate an improvement of motor function postoperatively. Therefore, transcranial electrical stimulation motor evoked potentials can be considered as a useful tool to the surgeon to monitor the quality of decompression of the spinal cord.

Removal of urothelium affects bladder contractility and release of ATP but not release of NO in rat urinary bladder.

PubMed

Munoz, Alvaro; Gangitano, David A; Smith, Christopher P; Boone, Timothy B; Somogyi, George T

2010-05-24

The objective of our work was to investigate both the contractile function and the release of ATP and NO from strips of bladder tissue after removal of the urothelium. The method of removal was a gentle swabbing motion rather than a sharp surgical cutting to separate the urothelium from the smooth muscle. The contractile response and ATP and NO release were measured in intact as well as on swabbed preparations. The removal of the urothelial layer was affirmed microscopically. After the swabbing, the smaller contractions were evoked by electrical as well as by chemical stimulation (50 microM carbachol or 50 microM alpha, beta meATP). Electrical stimulation, carbachol and substance P (5 microM) evoked lower release of ATP in the swabbed strips than in intact strips. Although release of NO evoked by electrical stimulation or substance P was not changed, release of NO evoked by carbachol was significantly less in the swabbed preparations. Since swabbing removes only the urothelium, the presence of the suburothelial layer may explain the difference between our findings and those of others who found an increase in contractility. Evoked release of ATP is reduced in swabbed strips, indicating that ATP derives solely from the urothelium. On the other hand, electrical stimulation and substance P evoke identical degrees of NO release in both intact and swabbed preparations, suggesting that NO can be released from the suburothelium. Conversely, carbachol-induced release of NO is lower in swabbed strips, implying that the cholinergic receptors (muscarinic or nicotinic) are located in the upper layer of the urothelium.

Noxious mechanical heterotopic stimulation induces inhibition of the spinal dorsal horn neuronal network: analysis of spinal somatosensory-evoked potentials.

PubMed

Meléndez-Gallardo, J; Eblen-Zajjur, A

2016-09-01

Most of the endogenous pain modulation (EPM) involves the spinal dorsal horn (SDH). EPM including diffuse noxious inhibitory controls have been extensively described in oligoneuronal electrophysiological recordings but less attention had been paid to responses of the SDH neuronal population to heterotopic noxious stimulation (HNS). Spinal somatosensory-evoked potentials (SEP) offer the possibility to evaluate the neuronal network behavior, reflecting the incoming afferent volleys along the entry root, SDH interneuron activities and the primary afferent depolarization. SEP from de lumbar cord dorsum were evaluated during mechanical heterotopic noxious stimuli. Sprague-Dawley rats (n = 12) were Laminectomized (T10-L3). The sural nerve of the left hind paw was electrically stimulated (5 mA, 0.5 ms, 0.05 Hz) to induce lumbar SEP. The HNS (mechanic clamp) was applied sequentially to the tail, right hind paw, right forepaw, muzzle and left forepaw during sural stimulation. N wave amplitude decreases (-16.6 %) compared to control conditions when HNS was applied to all areas of stimulation. This effect was more intense for muzzle stimulation (-23.5 %). N wave duration also decreased by -23.6 %. HNS did not change neither the amplitude nor the duration of the P wave but dramatically increases the dispersion of these two parameters. The results of the present study strongly suggest that a HNS applied to different parts of the body is able to reduce the integrated electrical response of the SDH, suggesting that not only wide dynamic range neurons but many others in the SDH are modulated by the EPM.

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Torres, Gonzalo E; Wagner, Amy K

2015-03-02

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. Copyright © 2015 Elsevier B.V. All rights reserved.

Vestibular evoked potentials (VsEPs) of cortical origin produced by impulsive acceleration applied at the nasion.

PubMed

Todd, Neil P M; McLean, Aisha; Paillard, Aurore; Kluk, Karolina; Colebatch, James G

2014-12-01

We report the results of a study to record vestibular evoked potentials (VsEPs) of cortical origin produced by impulsive acceleration (IA). In a sample of 12 healthy participants, evoked potentials recorded by 70 channel electroencephalography were obtained by IA stimulation at the nasion and compared with evoked potentials from the same stimulus applied to the forefingers. The nasion stimulation gave rise to a series of positive and negative deflections in the latency range of 26-72 ms, which were dependent on the polarity of the applied IA. In contrast, evoked potentials from the fingers were characterised by a single N50/P50 deflection at about 50 ms and were polarity invariant. Source analysis confirmed that the finger evoked potentials were somatosensory in origin, i.e. were somatosensory evoked potentials, and suggested that the nasion evoked potentials plausibly included vestibular midline and frontal sources, as well as contributions from the eyes, and thus were likely VsEPs. These results show considerable promise as a new method for assessment of the central vestibular system by means of VsEPs produced by IA applied to the head.

Bisensory stimulation increases gamma-responses over multiple cortical regions.

PubMed

Sakowitz, O W; Quiroga, R Q; Schürmann, M; Başar, E

2001-04-01

In the framework of the discussion about gamma (approx. 40 Hz) oscillations as information carriers in the brain, we investigated the relationship between gamma responses in the EEG and intersensory association. Auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) were compared with bisensory evoked potentials (BEPs; simultaneous auditory and visual stimulation) in 15 subjects. Gamma responses in AEPs, VEPs and BEPs were assessed by means of wavelet decomposition. Overall maximum gamma-components post-stimulus were highest in BEPs (P < 0.01). Bisensory evoked gamma-responses also showed significant central, parietal and occipital amplitude-increases (P < 0.001, P < 0.01, P < 0.05, respectively; prestimulus interval as baseline). These were of greater magnitude when compared with the unisensory responses. As a correlate of the marked gamma responses to bimodal stimulation we suggest a process of 'intersensory association', i.e. one of the steps between sensory transmission and perception. Our data may be interpreted as a further example of function-related gamma responses in the EEG.

Origin and Properties of Striatal Local Field Potential Responses to Cortical Stimulation: Temporal Regulation by Fast Inhibitory Connections

PubMed Central

Galiñanes, Gregorio L.; Braz, Barbara Y.; Murer, Mario Gustavo

2011-01-01

Evoked striatal field potentials are seldom used to study corticostriatal communication in vivo because little is known about their origin and significance. Here we show that striatal field responses evoked by stimulating the prelimbic cortex in mice are reduced by more than 90% after infusing the AMPA receptor antagonist CNQX close to the recording electrode. Moreover, the amplitude of local field responses and dPSPs recorded in striatal medium spiny neurons increase in parallel with increasing stimulating current intensity. Finally, the evoked striatal fields show several of the basic known properties of corticostriatal transmission, including paired pulse facilitation and topographical organization. As a case study, we characterized the effect of local GABAA receptor blockade on striatal field and multiunitary action potential responses to prelimbic cortex stimulation. Striatal activity was recorded through a 24 channel silicon probe at about 600 µm from a microdialysis probe. Intrastriatal administration of the GABAA receptor antagonist bicuculline increased by 65±7% the duration of the evoked field responses. Moreover, the associated action potential responses were markedly enhanced during bicuculline infusion. Bicuculline enhancement took place at all the striatal sites that showed a response to cortical stimulation before drug infusion, but sites showing no field response before bicuculline remained unresponsive during GABAA receptor blockade. Thus, the data demonstrate that fast inhibitory connections exert a marked temporal regulation of input-output transformations within spatially delimited striatal networks responding to a cortical input. Overall, we propose that evoked striatal fields may be a useful tool to study corticostriatal synaptic connectivity in relation to behavior. PMID:22163020

Characterization of Optically and Electrically Evoked Dopamine Release in Striatal Slices from Digenic Knock-in Mice with DAT-Driven Expression of Channelrhodopsin

PubMed Central

2017-01-01

Fast-scan cyclic voltammetry (FCV) is an established method to monitor increases in extracellular dopamine (DA) concentration ([DA]o) in the striatum, which is densely innervated by DA axons. Ex vivo brain slice preparations provide an opportunity to identify endogenous modulators of DA release. For these experiments, local electrical stimulation is often used to elicit release of DA, as well as other transmitters, in the striatal microcircuitry; changes in evoked increases in [DA]o after application of a pharmacological agent (e.g., a receptor antagonist) indicate a regulatory role for the transmitter system interrogated. Optogenetic methods that allow specific stimulation of DA axons provide a complementary, bottom-up approach for elucidating factors that regulate DA release. To this end, we have characterized DA release evoked by local electrical and optical stimulation in striatal slices from mice that genetically express a variant of channelrhodopsin-2 (ChR2). Evoked increases in [DA]o in the dorsal and ventral striatum (dStr and vStr) were examined in a cross of a Cre-dependent ChR2 line (“Ai32” mice) with a DAT::Cre mouse line. In dStr, repeated optical pulse-train stimulation at the same recording site resulted in rundown of evoked [DA]o using heterozygous mice, which contrasted with the stability seen with electrical stimulation. Similar rundown was seen in the presence of a nicotinic acetylcholine receptor (nAChR) antagonist, implicating the absence of concurrent nAChR activation in DA release instability in slices. Rundown with optical stimulation in dStr could be circumvented by recording from a population of sites, each stimulated only once. Same-site rundown was less pronounced with single-pulse stimulation, and a stable baseline could be attained. In vStr, stable optically evoked increases in [DA]o at single sites could be achieved using heterozygous mice, although with relatively low peak [DA]o. Low release could be overcome by using mice with a second copy of the Ai32 allele, which doubled ChR2 expression. The characteristics reported here should help future practitioners decide which Ai32;DAT::Cre genotype and recording protocol is optimal for the striatal subregion to be examined. PMID:28177213

Neural dynamics during repetitive visual stimulation

NASA Astrophysics Data System (ADS)

Tsoneva, Tsvetomira; Garcia-Molina, Gary; Desain, Peter

2015-12-01

Objective. Steady-state visual evoked potentials (SSVEPs), the brain responses to repetitive visual stimulation (RVS), are widely utilized in neuroscience. Their high signal-to-noise ratio and ability to entrain oscillatory brain activity are beneficial for their applications in brain-computer interfaces, investigation of neural processes underlying brain rhythmic activity (steady-state topography) and probing the causal role of brain rhythms in cognition and emotion. This paper aims at analyzing the space and time EEG dynamics in response to RVS at the frequency of stimulation and ongoing rhythms in the delta, theta, alpha, beta, and gamma bands. Approach.We used electroencephalography (EEG) to study the oscillatory brain dynamics during RVS at 10 frequencies in the gamma band (40-60 Hz). We collected an extensive EEG data set from 32 participants and analyzed the RVS evoked and induced responses in the time-frequency domain. Main results. Stable SSVEP over parieto-occipital sites was observed at each of the fundamental frequencies and their harmonics and sub-harmonics. Both the strength and the spatial propagation of the SSVEP response seem sensitive to stimulus frequency. The SSVEP was more localized around the parieto-occipital sites for higher frequencies (>54 Hz) and spread to fronto-central locations for lower frequencies. We observed a strong negative correlation between stimulation frequency and relative power change at that frequency, the first harmonic and the sub-harmonic components over occipital sites. Interestingly, over parietal sites for sub-harmonics a positive correlation of relative power change and stimulation frequency was found. A number of distinct patterns in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz) and beta (15-30 Hz) bands were also observed. The transient response, from 0 to about 300 ms after stimulation onset, was accompanied by increase in delta and theta power over fronto-central and occipital sites, which returned to baseline after approx. 500 ms. During the steady-state response, we observed alpha band desynchronization over occipital sites and after 500 ms also over frontal sites, while neighboring areas synchronized. The power in beta band over occipital sites increased during the stimulation period, possibly caused by increase in power at sub-harmonic frequencies of stimulation. Gamma power was also enhanced by the stimulation. Significance. These findings have direct implications on the use of RVS and SSVEPs for neural process investigation through steady-state topography, controlled entrainment of brain oscillations and BCIs. A deep understanding of SSVEP propagation in time and space and the link with ongoing brain rhythms is crucial for optimizing the typical SSVEP applications for studying, assisting, or augmenting human cognitive and sensorimotor function.

Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.

PubMed

Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

2011-03-23

Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not "equally sensitive" to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

Fluid Mechanics in Dentinal Microtubules Provides Mechanistic Insights into the Difference between Hot and Cold Dental Pain

PubMed Central

Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

2011-01-01

Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not “equally sensitive” to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices. PMID:21448459

Loss of lower limb motor evoked potentials and spinal cord injury during the initial exposure in scoliosis surgery.

PubMed

Legatt, Alan D; Fried, Stephen J; Amaral, Terry D; Sarwahi, Vishal; Moguilevitch, Marina

2014-04-01

To report a case of motor evoked potential changes and spinal cord injury during the initial dissection in scoliosis surgery. Motor evoked potentials to transcranial electrical stimulation were recorded from multiple muscles. Somatosensory evoked potentials to limb nerve stimulation were recorded from the scalp. Clear motor evoked potentials were initially present in all monitored muscles. The patient was then pharmacologically paralyzed for the initial dissection. More than usual bleeding was encountered during that dissection, prompting transfusion. As the neuromuscular blockade subsided, motor evoked potentials persisted in the hand muscles but disappeared and remained absent in all monitored leg muscles. The spine had not been instrumented. A wake-up test demonstrated paraplegia; the surgery was aborted. There were no adverse somatosensory evoked potential changes. MRI showed an anterior spinal cord infarct. Copious soft tissue bleeding during the initial dissection might have lowered pressures in critical segmental arteries enough to cause spinal cord infarction through a steal phenomenon. The lack of somatosensory evoked potential changes reflected sparing of the dorsal columns. When neuromuscular blockade is used during the initial soft tissue dissection, motor evoked potentials should be assessed after this, but before spinal instrumentation, to determine whether there had been any spinal cord compromise during the initial dissection.

Claustral single cell reactions to tooth pulp stimulation in cats.

PubMed

Jastreboff, P; Sikora, M; Frydrychowski, A; Słoniewski, P

1983-01-01

Single unit activity in the central region of the claustrum, evoked by electrical stimulation of tooth pulp or paws was studied on cats under chloralose anesthesia. The majority of cells responded in similar manner to stimulation of tooth pulp or paws, but there were cells with clear preference to a given type of stimulation. Latencies of reactions evoked by tooth pulp stimulation were significantly shorter than those for limb stimulation. In the former case latencies as short as 8 rns were observed. It is postulated that the central region of the claustrum receives a projection from the tooth pulp, and that in those cases with very short latency the projection is direct and does not involve the cerebral cortex.

Lateral geniculate body evoked potentials elicited by visual and electrical stimulation.

PubMed

Choi, Chang Wook; Kim, Pan Sang; Shin, Sun Ae; Yang, Ji Yeon; Yang, Yun Sik

2014-08-01

Blind individuals who have photoreceptor loss are known to perceive phosphenes with electrical stimulation of their remaining retinal ganglion cells. We proposed that implantable lateral geniculate body (LGB) stimulus electrode arrays could be used to generate phosphene vision. We attempted to refine the basic reference of the electrical evoked potentials (EEPs) elicited by microelectrical stimulations of the optic nerve, optic tract and LGB of a domestic pig, and then compared it to visual evoked potentials (VEPs) elicited by short-flash stimuli. For visual function measurement, VEPs in response to short-flash stimuli on the left eye of the domestic pig were assessed over the visual cortex at position Oz with the reference electrode at Fz. After anesthesia, linearly configured platinum wire electrodes were inserted into the optic nerve, optic track and LGB. To determine the optimal stimulus current, EEPs were recorded repeatedly with controlling the pulse and power. The threshold of current and charge density to elicit EEPs at 0.3 ms pulse duration was about ±10 µA. Our experimental results showed that visual cortex activity can be effectively evoked by stimulation of the optic nerve, optic tract and LGB using penetrating electrodes. The latency of P1 was more shortened as the electrical stimulation was closer to LGB. The EEPs of two-channel in the visual cortex demonstrated a similar pattern with stimulation of different spots of the stimulating electrodes. We found that the LGB-stimulated EEP pattern was very similar to the simultaneously generated VEP on the control side, although implicit time deferred. EEPs and VEPs derived from visual-system stimulation were compared. The LGB-stimulated EEP wave demonstrated a similar pattern to the VEP waveform except implicit time, indicating prosthetic-based electrical stimulation of the LGB could be utilized for the blind to perceive vision of phosphenes.

Effect of Fiberoptic Collimation Technique on 808 nm Wavelength Laser Stimulation of Cochlear Neurons.

PubMed

Wang, Jingxuan; Lu, Jianren; Tian, Lan

2016-06-01

The purpose of this study was to evaluate the effects of fiberoptic collimation technique on auditory neural stimulation in the cochlea with 808 nm wavelength lasers. Recently, the pulsed near-infrared lasers in the 800-1000 nm wavelength range have been investigated as an emerging technique to trigger auditory neural response in the cochlea. A laser beam divergence in the optical stimulation pathway exists, which may affect stimulation efficiency and spatial selectivity. The fiberoptic collimation technique was proposed for cochlear neuron stimulation, and the C-lens element was designed as the collimation structure. The spiral ganglion cells in deafened guinea pigs' cochlea were irradiated with collimated and uncollimated near-infrared lasers. Optically evoked auditory brainstem response (OABR) under the two laser output modes were recorded. Laser with the collimation technique evoked an average 58% higher OABR amplitude than the uncollimated laser output. In addition, the collimated laser setup consumed on average 35.2% of laser energy compared with the uncollimated laser when evoking the same OABR amplitude. The fiberoptic collimation technique improved stimulation efficiency and reduced stimulating energy consumption in near-infrared neural stimulation in cochlea. The positive effects of laser collimation technique could benefit further research in optically based cochlear implants.

Sustained signalling by PTH modulates IP3 accumulation and IP3 receptors through cyclic AMP junctions

PubMed Central

Meena, Abha; Tovey, Stephen C.; Taylor, Colin W.

2015-01-01

ABSTRACT Parathyroid hormone (PTH) stimulates adenylyl cyclase through type 1 PTH receptors (PTH1R) and potentiates the Ca2+ signals evoked by carbachol, which stimulates formation of inositol 1,4,5-trisphosphate (IP3). We confirmed that in HEK cells expressing PTH1R, acute stimulation with PTH(1-34) potentiated carbachol-evoked Ca2+ release. This was mediated by locally delivered cyclic AMP (cAMP), but unaffected by inhibition of protein kinase A (PKA), exchange proteins activated by cAMP, cAMP phosphodiesterases (PDEs) or substantial inhibition of adenylyl cyclase. Sustained stimulation with PTH(1-34) causes internalization of PTH1R–adenylyl cyclase signalling complexes, but the consequences for delivery of cAMP to IP3R within cAMP signalling junctions are unknown. Here, we show that sustained stimulation with PTH(1-34) or with PTH analogues that do not evoke receptor internalization reduced the potentiated Ca2+ signals and attenuated carbachol-evoked increases in cytosolic IP3. Similar results were obtained after sustained stimulation with NKH477 to directly activate adenylyl cyclase, or with the membrane-permeant analogue of cAMP, 8-Br-cAMP. These responses were independent of PKA and unaffected by substantial inhibition of adenylyl cyclase. During prolonged stimulation with PTH(1-34), hyperactive cAMP signalling junctions, within which cAMP is delivered directly and at saturating concentrations to its targets, mediate sensitization of IP3R and a more slowly developing inhibition of IP3 accumulation. PMID:25431134

Influence of detomidine and buprenorphine on motor-evoked potentials in horses.

PubMed

Nollet, H; Van Ham, L; Gasthuys, F; Dewulf, J; Vanderstraeten, G; Deprez, P

2003-04-26

Horses need to be sedated before they are investigated by transcranial magnetic stimulation because of the mild discomfort induced by the evoked muscle contraction and the noise of stimulation. This paper describes the influence of a combination of detomidine (10 microg/kg bodyweight) and a low dose of buprenorphine (2.4 microg/kg) on the onset latency and peak-to-peak amplitude of magnetic motor-evoked potentials in normal horses. There were no significant differences between measurements of these parameters made before the horses were sedated and measurements made 10 and 30 minutes after the drugs were administered.

Colonic motor and vascular responses to pelvic nerve stimulation and their relation to local peptide release in the cat.

PubMed Central

Andersson, P O; Bloom, S R; Järhult, J

1983-01-01

1. The effects of stimulation of the pelvic nerves in atropinized cats at continuous, low frequencies from 1 to 16 Hz (continuous stimulation) were compared with those of stimulation at higher frequencies (10-160 Hz) delivered in 1 s bursts at 10 s intervals (stimulation in bursts), the latter simulating a commonly observed discharge pattern in vivo. Both types of stimulation evoked a transient vasodilatation. Stimulation in bursts at 20 and 40 Hz evoked more pronounced vasodilatations than continuous stimulation delivering exactly the same number of impulses over the whole period of excitation. 2. Stimulation of the pelvic nerves in bursts failed to elicit an effective contraction of the colon at any frequency tested, whereas continuous stimulation invariably evoked a contraction. 3. There was a clear-cut increase in the output of vasoactive intestinal polypeptide during both continuous and intermittent stimulation of the pelvic nerves. Stimulation in bursts caused a small but significant increase in the output of somatostatin but there was no change in the output of substance P in response to either type of pelvic nerve stimulation. 4. The colonic muscular contraction in response to continuous stimulation of the pelvic nerves was not affected by somatostatin when infused intra-arterially at the large dose of 1.0 microgram/min. 5. It is concluded that the colonic responses of atropinized cats to pelvic nerve stimulation can be substantially altered merely by changing the pattern of stimulation. Thus, whereas continuous stimulation produces both muscular contraction and vasodilatation, stimulation in bursts favours vasodilatation but is ineffective in eliciting colonic contraction. PMID:6191025

A non-capacitative pathway activated by arachidonic acid is the major Ca2+ entry mechanism in rat A7r5 smooth muscle cells stimulated with low concentrations of vasopressin

PubMed Central

Broad, Lisa M; Cannon, Toby R; Taylor, Colin W

1999-01-01

Depletion of the Ca2+ stores of A7r5 cells stimulated Ca2+, though not Sr2+, entry. Vasopressin (AVP) or platelet-derived growth factor (PDGF) stimulated Sr2+ entry. The cells therefore express a capacitative pathway activated by empty stores and a non-capacitative pathway stimulated by receptors; only the former is permeable to Mn2+ and only the latter to Sr2+. Neither empty stores nor inositol 1,4,5-trisphosphate (InsP3) binding to its receptors are required for activation of the non-capacitative pathway, because microinjection of cells with heparin prevented PDGF-evoked Ca2+ mobilization but not Sr2+ entry. Low concentrations of Gd3+ irreversibly blocked capacitative Ca2+ entry without affecting AVP-evoked Sr2+ entry. After inhibition of the capacitative pathway with Gd3+, AVP evoked a substantial increase in cytosolic [Ca2+], confirming that the non-capacitative pathway can evoke a significant increase in cytosolic [Ca2+]. Arachidonic acid mimicked the effect of AVP on Sr2+ entry without stimulating Mn2+ entry; the Sr2+ entry was inhibited by 100 μM Gd3+, but not by 1 μM Gd3+ which completely inhibited capacitative Ca2+ entry. The effects of arachidonic acid did not require its metabolism. AVP-evoked Sr2+ entry was unaffected by isotetrandrine, an inhibitor of G protein-coupled phospholipase A2. U73122, an inhibitor of phosphoinositidase C, inhibited AVP-evoked formation of inositol phosphates and Sr2+ entry. The effects of phorbol esters and Ro31-8220 (a protein kinase C inhibitor) established that protein kinase C did not mediate the effects of AVP on the non-capacitative pathway. An inhibitor of diacylglycerol lipase, RHC-80267, inhibited AVP-evoked Sr2+ entry without affecting capacitative Ca2+ entry or release of Ca2+ stores. Selective inhibition of capacitative Ca2+ entry with Gd3+ revealed that the non-capacitative pathway is the major route for the Ca2+ entry evoked by low AVP concentrations. We conclude that in A7r5 cells, the Ca2+ entry evoked by low concentrations of AVP is mediated largely by a non-capacitative pathway directly regulated by arachidonic acid produced by the sequential activities of phosphoinositidase C and diacylglycerol lipase. PMID:10226154

The effects of neck flexion on cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in related sensory cortices

PubMed Central

2012-01-01

Background A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices. Methods Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10–20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy. Results Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position. Conclusions Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections. PMID:23199306

Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells.

PubMed

Fernández-Sánchez, Marcela; del Castillo-Vaquero, Angel; Salido, Ginés M; González, Antonio

2009-10-30

A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca2+ signals in mouse pancreatic acinar cells. Changes in [Ca2+]i and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H2DCFDA, respectively. Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca2+]i. In addition, ethanol evoked reactive oxygen species generation (ROS) production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca2+]i. In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca2+]i in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca2+ mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 microM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca2+ mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production. ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca2+ mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.

Thermoreceptive innervation of human glabrous and hairy skin: a contact heat evoked potential analysis.

PubMed

Granovsky, Yelena; Matre, Dagfinn; Sokolik, Alexander; Lorenz, Jürgen; Casey, Kenneth L

2005-06-01

The human palm has a lower heat detection threshold and a higher heat pain threshold than hairy skin. Neurophysiological studies of monkeys suggest that glabrous skin has fewer low threshold heat nociceptors (AMH type 2) than hairy skin. Accordingly, we used a temperature-controlled contact heat evoked potential (CHEP) stimulator to excite selectively heat receptors with C fibers or Adelta-innervated AMH type 2 receptors in humans. On the dorsal hand, 51 degrees C stimulation produced painful pinprick sensations and 41 degrees C stimuli evoked warmth. On the glabrous thenar, 41 degrees C stimulation produced mild warmth and 51 degrees C evoked strong but painless heat sensations. We used CHEP responses to estimate the conduction velocities (CV) of peripheral fibers mediating these sensations. On hairy skin, 41 degrees C stimuli evoked an ultra-late potential (mean, SD; N wave latency: 455 (118) ms) mediated by C fibers (CV by regression analysis: 1.28 m/s, N=15) whereas 51 degrees C stimuli evoked a late potential (N latency: 267 (33) ms) mediated by Adelta afferents (CV by within-subject analysis: 12.9 m/s, N=6). In contrast, thenar responses to 41 and 51 degrees C were mediated by C fibers (average N wave latencies 485 (100) and 433 (73) ms, respectively; CVs 0.95-1.35 m/s by regression analysis, N=15; average CV=1.7 (0.41) m/s calculated from distal glabrous and proximal hairy skin stimulation, N=6). The exploratory range of the human and monkey palm is enhanced by the abundance of low threshold, C-innervated heat receptors and the paucity of low threshold AMH type 2 heat nociceptors.

Electrical stimulus artifact cancellation and neural spike detection on large multi-electrode arrays

PubMed Central

Grosberg, Lauren E.; Madugula, Sasidhar; Litke, Alan; Cunningham, John; Chichilnisky, E. J.; Paninski, Liam

2017-01-01

Simultaneous electrical stimulation and recording using multi-electrode arrays can provide a valuable technique for studying circuit connectivity and engineering neural interfaces. However, interpreting these measurements is challenging because the spike sorting process (identifying and segregating action potentials arising from different neurons) is greatly complicated by electrical stimulation artifacts across the array, which can exhibit complex and nonlinear waveforms, and overlap temporarily with evoked spikes. Here we develop a scalable algorithm based on a structured Gaussian Process model to estimate the artifact and identify evoked spikes. The effectiveness of our methods is demonstrated in both real and simulated 512-electrode recordings in the peripheral primate retina with single-electrode and several types of multi-electrode stimulation. We establish small error rates in the identification of evoked spikes, with a computational complexity that is compatible with real-time data analysis. This technology may be helpful in the design of future high-resolution sensory prostheses based on tailored stimulation (e.g., retinal prostheses), and for closed-loop neural stimulation at a much larger scale than currently possible. PMID:29131818

Electrical stimulus artifact cancellation and neural spike detection on large multi-electrode arrays.

PubMed

Mena, Gonzalo E; Grosberg, Lauren E; Madugula, Sasidhar; Hottowy, Paweł; Litke, Alan; Cunningham, John; Chichilnisky, E J; Paninski, Liam

2017-11-01

Simultaneous electrical stimulation and recording using multi-electrode arrays can provide a valuable technique for studying circuit connectivity and engineering neural interfaces. However, interpreting these measurements is challenging because the spike sorting process (identifying and segregating action potentials arising from different neurons) is greatly complicated by electrical stimulation artifacts across the array, which can exhibit complex and nonlinear waveforms, and overlap temporarily with evoked spikes. Here we develop a scalable algorithm based on a structured Gaussian Process model to estimate the artifact and identify evoked spikes. The effectiveness of our methods is demonstrated in both real and simulated 512-electrode recordings in the peripheral primate retina with single-electrode and several types of multi-electrode stimulation. We establish small error rates in the identification of evoked spikes, with a computational complexity that is compatible with real-time data analysis. This technology may be helpful in the design of future high-resolution sensory prostheses based on tailored stimulation (e.g., retinal prostheses), and for closed-loop neural stimulation at a much larger scale than currently possible.

Identification of visual evoked response parameters sensitive to pilot mental state

NASA Technical Reports Server (NTRS)

Zacharias, G. L.

1988-01-01

Systems analysis techniques were developed and demonstrated for modeling the electroencephalographic (EEG) steady state visual evoked response (ssVER), for use in EEG data compression and as an indicator of mental workload. The study focused on steady state frequency domain stimulation and response analysis, implemented with a sum-of-sines (SOS) stimulus generator and an off-line describing function response analyzer. Three major tasks were conducted: (1) VER related systems identification material was reviewed; (2) Software for experiment control and data analysis was developed and implemented; and (3) ssVER identification and modeling was demonstrated, via a mental loading experiment. It was found that a systems approach to ssVER functional modeling can serve as the basis for eventual development of a mental workload indicator. The review showed how transient visual evoked response (tVER) and ssVER research are related at the functional level, the software development showed how systems techniques can be used for ssVER characterization, and the pilot experiment showed how a simple model can be used to capture the basic dynamic response of the ssVER, under varying loads.

Synaptic potentials in respiratory neurones during evoked phase switching after NMDA receptor blockade in the cat

PubMed Central

Pierrefiche, O; Haji, A; Foutz, A S; Takeda, R; Champagnat, J; Denavit-Saubié, M

1998-01-01

Blockade of NMDA receptors by dizocilpine impairs the inspiratory off-switch (IOS) of central origin but not the IOS evoked by stimulation of sensory afferents. To investigate whether this difference was due to the effects of different patterns of synaptic interactions on respiratory neurones, we stimulated electrically the superior laryngeal nerve (SLN) or vagus nerve in decerebrate cats before and after i.v. administration of dizocilpine, whilst recording intracellularly. Phrenic nerve responses to ipsilateral SLN or vagal stimulation were: at mid-inspiration, a transient inhibition often followed by a brief burst of activity; at late inspiration, an IOS; and at mid-expiration, a late burst of activity. In all neurones (n = 16), SLN stimulation at mid-inspiration evoked an early EPSP during phase 1 (latency to the arrest of phrenic nerve activity), followed by an IPSP in inspiratory (I) neurones (n = 8) and by a wave of EPSPs in post-inspiratory (PI) neurones (n = 8) during phase 2 (inhibition of phrenic activity). An EPSP in I neurones and an IPSP in PI neurones occurred during phase 3 (brief phrenic burst) following phase 2. Evoked IOS was associated with a fast (phase 1) activation of PI neurones, whereas during spontaneous IOS, a progressive (30-50 ms) depolarization of PI neurones preceded the arrest of phrenic activity. Phase 3 PSPs were similar to those occurring during the burst of activity seen at the start of spontaneous inspiration. Dizocilpine did not suppress the evoked phrenic inhibition and the late burst of activity. The shapes and timing of the evoked PSPs and the changes in membrane potential in I and PI neurones during the phase transition were not altered. We hypothesize that afferent sensory pathways not requiring NMDA receptors (1) terminate inspiration through a premature activation of PI neurones, and (2) evoke a late burst of phrenic activity which might be the first stage of the inspiratory on-switch. PMID:9508816

Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control.

PubMed

Ardell, Jeffrey L; Nier, Heath; Hammer, Matthew; Southerland, E Marie; Ardell, Christopher L; Beaumont, Eric; KenKnight, Bruce H; Armour, J Andrew

2017-11-15

The evoked cardiac response to bipolar cervical vagus nerve stimulation (VNS) reflects a dynamic interaction between afferent mediated decreases in central parasympathetic drive and suppressive effects evoked by direct stimulation of parasympathetic efferent axons to the heart. The neural fulcrum is defined as the operating point, based on frequency-amplitude-pulse width, where a null heart rate response is reproducibly evoked during the on-phase of VNS. Cardiac control, based on the principal of the neural fulcrum, can be elicited from either vagus. Beta-receptor blockade does not alter the tachycardia phase to low intensity VNS, but can increase the bradycardia to higher intensity VNS. While muscarinic cholinergic blockade prevented the VNS-induced bradycardia, clinically relevant doses of ACE inhibitors, beta-blockade and the funny channel blocker ivabradine did not alter the VNS chronotropic response. While there are qualitative differences in VNS heart control between awake and anaesthetized states, the physiological expression of the neural fulcrum is maintained. Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, 'cardiac' configuration) or with electrode positions reversed (n = 8, 'epilepsy' configuration). In awake state, HRRs were determined for each combination of pulse frequency (2-20 Hz), intensity (0-3.5 mA) and pulse widths (130-750 μs) over 14 months. At low intensities and higher frequency VNS, HR increased during the VNS active phase owing to afferent modulation of parasympathetic central drive. When functional effects of afferent and efferent fibre activation were balanced, a null HRR was evoked (defined as 'neural fulcrum') during which HRR ≈ 0. As intensity increased further, HR was reduced during the active phase of VNS. While qualitatively similar, VNS delivered in the epilepsy configuration resulted in more pronounced HR acceleration and reduced HR deceleration during VNS. At termination, under anaesthesia, transection of the vagi rostral to the stimulation site eliminated the augmenting response to VNS and enhanced the parasympathetic efferent-mediated suppressing effect on electrical and mechanical function of the heart. In conclusion, VNS activates central then peripheral aspects of the cardiac nervous system. VNS control over cardiac function is maintained during chronic therapy. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Oscillatory frontal theta responses are increased upon bisensory stimulation.

PubMed

Sakowitz, O W; Schürmann, M; Başar, E

2000-05-01

To investigate the functional correlation of oscillatory EEG components with the interaction of sensory modalities following simultaneous audio-visual stimulation. In an experimental study (15 subjects) we compared auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) to bimodal evoked potentials (BEPs; simultaneous auditory and visual stimulation). BEPs were assumed to be brain responses to complex stimuli as a marker for intermodal associative functioning. Frequency domain analysis of these EPs showed marked theta-range components in response to bimodal stimulation. These theta components could not be explained by linear addition of the unimodal responses in the time domain. Considering topography the increased theta-response showed a remarkable frontality in proximity to multimodal association cortices. Referring to methodology we try to demonstrate that, even if various behavioral correlates of brain oscillations exist, common patterns can be extracted by means of a systems-theoretical approach. Serving as an example of functionally relevant brain oscillations, theta responses could be interpreted as an indicator of associative information processing.

High frequency switched-mode stimulation can evoke post synaptic responses in cerebellar principal neurons

PubMed Central

van Dongen, Marijn N.; Hoebeek, Freek E.; Koekkoek, S. K. E.; De Zeeuw, Chris I.; Serdijn, Wouter A.

2015-01-01

This paper investigates the efficacy of high frequency switched-mode neural stimulation. Instead of using a constant stimulation amplitude, the stimulus is switched on and off repeatedly with a high frequency (up to 100 kHz) duty cycled signal. By means of tissue modeling that includes the dynamic properties of both the tissue material as well as the axon membrane, it is first shown that switched-mode stimulation depolarizes the cell membrane in a similar way as classical constant amplitude stimulation. These findings are subsequently verified using in vitro experiments in which the response of a Purkinje cell is measured due to a stimulation signal in the molecular layer of the cerebellum of a mouse. For this purpose a stimulator circuit is developed that is able to produce a monophasic high frequency switched-mode stimulation signal. The results confirm the modeling by showing that switched-mode stimulation is able to induce similar responses in the Purkinje cell as classical stimulation using a constant current source. This conclusion opens up possibilities for novel stimulation designs that can improve the performance of the stimulator circuitry. Care has to be taken to avoid losses in the system due to the higher operating frequency. PMID:25798105

Eliciting naturalistic cortical responses with a sensory prosthesis via optimized microstimulation

NASA Astrophysics Data System (ADS)

Choi, John S.; Brockmeier, Austin J.; McNiel, David B.; von Kraus, Lee M.; Príncipe, José C.; Francis, Joseph T.

2016-10-01

Objective. Lost sensations, such as touch, could one day be restored by electrical stimulation along the sensory neural pathways. Such stimulation, when informed by electronic sensors, could provide naturalistic cutaneous and proprioceptive feedback to the user. Perceptually, microstimulation of somatosensory brain regions produces localized, modality-specific sensations, and several spatiotemporal parameters have been studied for their discernibility. However, systematic methods for encoding a wide array of naturally occurring stimuli into biomimetic percepts via multi-channel microstimulation are lacking. More specifically, generating spatiotemporal patterns for explicitly evoking naturalistic neural activation has not yet been explored. Approach. We address this problem by first modeling the dynamical input-output relationship between multichannel microstimulation and downstream neural responses, and then optimizing the input pattern to reproduce naturally occurring touch responses as closely as possible. Main results. Here we show that such optimization produces responses in the S1 cortex of the anesthetized rat that are highly similar to natural, tactile-stimulus-evoked counterparts. Furthermore, information on both pressure and location of the touch stimulus was found to be highly preserved. Significance. Our results suggest that the currently presented stimulus optimization approach holds great promise for restoring naturalistic levels of sensation.

Glinide, but Not Sulfonylurea, Can Evoke Insulin Exocytosis by Repetitive Stimulation: Imaging Analysis of Insulin Exocytosis by Secretagogue-Induced Repetitive Stimulations

PubMed Central

Aoyagi, Kyota; Ohara-Imaizumi, Mica; Nishiwaki, Chiyono; Nakamichi, Yoko; Nagamatsu, Shinya

2009-01-01

To investigate the different effects between sulfonylurea (SU) and glinide drugs in insulin secretion, pancreatic β-cells were repeatedly stimulated with SU (glimepiride) or glinide (mitiglinide). Total internal reflection fluorescent (TIRF) microscopy revealed that secondary stimulation with glimepiride, but not glucose and mitiglinide, failed to evoke fusions of insulin granules although primary stimulation with glucose, glimepiride, and mitiglinide induced equivalent numbers of exocytotic responses. Glimepiride, but not glucose and mitiglinide, induced abnormally sustained [Ca2+]i elevations and reductions of docked insulin granules on the plasma membrane. Our data suggest that the effect of glinide on insulin secretory mechanisms is similar to that of glucose. PMID:20069052

Steady-state visual evoked potential (SSVEP)-based communication: impact of harmonic frequency components

NASA Astrophysics Data System (ADS)

Müller-Putz, Gernot R.; Scherer, Reinhold; Brauneis, Christian; Pfurtscheller, Gert

2005-12-01

Brain-computer interfaces (BCIs) can be realized on the basis of steady-state evoked potentials (SSEPs). These types of brain signals resulting from repetitive stimulation have the same fundamental frequency as the stimulation but also include higher harmonics. This study investigated how the classification accuracy of a 4-class BCI system can be improved by incorporating visually evoked harmonic oscillations. The current study revealed that the use of three SSVEP harmonics yielded a significantly higher classification accuracy than was the case for one or two harmonics. During feedback experiments, the five subjects investigated reached a classification accuracy between 42.5% and 94.4%.

Steady-state visual evoked potential (SSVEP)-based communication: impact of harmonic frequency components.

PubMed

Müller-Putz, Gernot R; Scherer, Reinhold; Brauneis, Christian; Pfurtscheller, Gert

2005-12-01

Brain-computer interfaces (BCIs) can be realized on the basis of steady-state evoked potentials (SSEPs). These types of brain signals resulting from repetitive stimulation have the same fundamental frequency as the stimulation but also include higher harmonics. This study investigated how the classification accuracy of a 4-class BCI system can be improved by incorporating visually evoked harmonic oscillations. The current study revealed that the use of three SSVEP harmonics yielded a significantly higher classification accuracy than was the case for one or two harmonics. During feedback experiments, the five subjects investigated reached a classification accuracy between 42.5% and 94.4%.

Role of the parabrachial complex in the cardiorespiratory response evoked from hypothalamic defense area stimulation in the anesthetized rat.

PubMed

Díaz-Casares, Amelia; López-González, Manuel Víctor; Peinado-Aragonés, Carlos Antonio; Lara, José Pablo; González-Barón, Salvador; Dawid-Milner, Marc Stefan

2009-07-07

To analyze the role of parabrachial complex (PBc) in the modulation of cardiorespiratory response evoked from the hypothalamic defense area (HDA), cardiorespiratory changes were analyzed in spontaneously breathing anesthetised rats in response to electrical stimulation of the HDA (1 ms pulses, 30-50 microA, 100 Hz for 5 s) before and after the microinjection of muscimol (50 nl, 0.25 nmol, 5 s) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (p<0.001) due to a decrease in expiratory time (p<0.01). The respiratory response was accompanied by a pressor (p<0.001) and a tachycardic (p<0.001) response. Muscimol microinjection within the lateral parabrachial region (lPB) abolished the respiratory response to HDA stimulation (p<0.01) and decreased the pressor response (p<0.05). Muscimol within the medial parabrachial region and Kölliker-Fuse (mPB-KF) decreased the magnitude of the pressor (p<0.01) and tachycardic (p<0.05) responses to HDA stimulation. The respiratory response persisted unchanged. Finally, extracellular recording of putative neurons from these regions were obtained during HDA stimulation to confirm functional interaction between HDA and parabrachial regions. 105 pontine cells were recorded during HDA stimulation, 57 from the lPB and 48 from the mPB-KF. In mPB-KF 34/48 (71%) and in lPB 38/57 (67%) cells were influenced from HDA. The results indicate that neurons from different regions of the PBc have an important function in mediating the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

Selective processing of auditory evoked responses with iterative-randomized stimulation and averaging: A strategy for evaluating the time-invariant assumption.

PubMed

Valderrama, Joaquin T; de la Torre, Angel; Medina, Carlos; Segura, Jose C; Thornton, A Roger D

2016-03-01

The recording of auditory evoked potentials (AEPs) at fast rates allows the study of neural adaptation, improves accuracy in estimating hearing threshold and may help diagnosing certain pathologies. Stimulation sequences used to record AEPs at fast rates require to be designed with a certain jitter, i.e., not periodical. Some authors believe that stimuli from wide-jittered sequences may evoke auditory responses of different morphology, and therefore, the time-invariant assumption would not be accomplished. This paper describes a methodology that can be used to analyze the time-invariant assumption in jittered stimulation sequences. The proposed method [Split-IRSA] is based on an extended version of the iterative randomized stimulation and averaging (IRSA) technique, including selective processing of sweeps according to a predefined criterion. The fundamentals, the mathematical basis and relevant implementation guidelines of this technique are presented in this paper. The results of this study show that Split-IRSA presents an adequate performance and that both fast and slow mechanisms of adaptation influence the evoked-response morphology, thus both mechanisms should be considered when time-invariance is assumed. The significance of these findings is discussed. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Adaptive changes in the neuromagnetic response of the primary and association somatosensory areas following repetitive tactile hand stimulation in humans.

PubMed

Popescu, Elena Anda; Barlow, Steven M; Venkatesan, Lalit; Wang, Jingyan; Popescu, Mihai

2013-06-01

Cortical adaptation in the primary somatosensory cortex (SI) has been probed using different stimulation modalities and recording techniques, in both human and animal studies. In contrast, considerably less knowledge has been gained about the adaptation profiles in other areas of the cortical somatosensory network. Using magnetoencephalography (MEG), we examined the patterns of short-term adaptation for evoked responses in SI and somatosensory association areas during tactile stimulation applied to the glabrous skin of the hand. Cutaneous stimuli were delivered as trains of serial pulses with a constant frequency of 2 Hz and 4 Hz in separate runs, and a constant inter-train interval of 5 s. The unilateral stimuli elicited transient responses to the serial pulses in the train, with several response components that were separated by independent component analysis. Subsequent source reconstruction techniques identified regional generators in the contralateral SI and somatosensory association areas in the posterior parietal cortex (PPC). Activity in the bilateral secondary somatosensory cortex (i.e., SII/PV) was also identified, although less consistently across subjects. The dynamics of the evoked activity in each area and the frequency-dependent adaptation effects were assessed from the changes in the relative amplitude of serial responses in each train. We show that the adaptation profiles in SI and PPC areas can be quantitatively characterized from neuromagnetic recordings using tactile stimulation, with the sensitivity to repetitive stimulation increasing from SI to PPC. A similar approach for SII/PV has proven less straightforward, potentially due to the tendency of these areas to respond selectively to certain stimuli. Copyright © 2011 Wiley Periodicals, Inc.

Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin

PubMed Central

Dickenson, Anthony H.

2016-01-01

Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a “WDR phenotype.” After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. PMID:27098028

Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.

PubMed

Patel, Ryan; Dickenson, Anthony H

2016-07-01

Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.

Quantification of the proportion of motor neurons recruited by transcranial electrical stimulation during intraoperative motor evoked potential monitoring.

PubMed

Tsutsui, Shunji; Yamada, Hiroshi; Hashizume, Hiroshi; Minamide, Akihito; Nakagawa, Yukihiro; Iwasaki, Hiroshi; Yoshida, Munehito

2013-12-01

Transcranial motor evoked potentials (TcMEPs) are widely used to monitor motor function during spinal surgery. However, they are much smaller and more variable in amplitude than responses evoked by maximal peripheral nerve stimulation, suggesting that a limited number of spinal motor neurons to the target muscle are excited by transcranial stimulation. The aim of this study was to quantify the proportion of motor neurons recruited during TcMEP monitoring under general anesthesia. In twenty patients who underwent thoracic and/or lumbar spinal surgery with TcMEP monitoring, the triple stimulation technique (TST) was applied to the unilateral upper arm intraoperatively. Total intravenous anesthesia was employed. Trains of four stimuli were delivered with maximal intensity and an inter-pulse interval of 1.5 ms. TST responses were recorded from the abductor digiti minimi muscle, and the negative peak amplitude and area were measured and compared between the TST test (two collisions between transcranial and proximal and distal peripheral stimulation) and control response (two collisions between two proximal and one distal peripheral stimulation). The highest degree of superimposition of the TST test and control responses was chosen from several trials per patient. The average ratios (test:control) were 17.1 % (range 1.8-38 %) for the amplitudes and 21.6 % (range 2.9-40 %) for the areas. The activity of approximately 80 % of the motor units to the target muscle cannot be detected by TcMEP monitoring. Therefore, changes in evoked potentials must be interpreted cautiously when assessing segmental motor function with TcMEP monitoring.

Electrical stimulation of the rostral medial prefrontal cortex in rabbits inhibits the expression of conditioned eyelid responses but not their acquisition

PubMed Central

Leal-Campanario, Rocío; Fairén, Alfonso; Delgado-García, José M.; Gruart, Agnès

2007-01-01

We have studied the role of rostral medial prefrontal cortex (mPFC) on reflexively evoked blinks and on classically conditioned eyelid responses in alert-behaving rabbits. The rostral mPFC was identified by its afferent projections from the medial half of the thalamic mediodorsal nuclear complex. Classical conditioning consisted of a delay paradigm using a 370-ms tone as the conditioned stimulus (CS) and a 100-ms air puff directed at the left cornea as the unconditioned stimulus (US). The CS coterminated with the US. Electrical train stimulation of the contralateral rostral mPFC produced a significant inhibition of air-puff-evoked blinks. The same train stimulation of the rostral mPFC presented during the CS–US interval for 10 successive conditioning sessions significantly reduced the generation of conditioned responses (CRs) as compared with values reached by control animals. Interestingly, the percentage of CRs almost reached control values when train stimulation of the rostral mPFC was removed from the fifth conditioning session on. The electrical stimulation of the rostral mPFC in well conditioned animals produced a significant decrease in the percentage of CRs. Moreover, the stimulation of the rostral mPFC was also able to modify the kinematics (latency, amplitude, and velocity) of evoked CRs. These results suggest that the rostral mPFC is a potent inhibitor of reflexively evoked and classically conditioned eyeblinks but that activation prevents only the expression of CRs, not their latent acquisition. Functional and behavioral implications of this inhibitory role of the rostral mPFC are discussed. PMID:17592148

Sparse and Specific Coding during Information Transmission between Co-cultured Dentate Gyrus and CA3 Hippocampal Networks

PubMed Central

Poli, Daniele; Thiagarajan, Srikanth; DeMarse, Thomas B.; Wheeler, Bruce C.; Brewer, Gregory J.

2017-01-01

To better understand encoding and decoding of stimulus information in two specific hippocampal sub-regions, we isolated and co-cultured rat primary dentate gyrus (DG) and CA3 neurons within a two-chamber device with axonal connectivity via micro-tunnels. We tested the hypothesis that, in these engineered networks, decoding performance of stimulus site information would be more accurate when stimuli and information flow occur in anatomically correct feed-forward DG to CA3 vs. CA3 back to DG. In particular, we characterized the neural code of these sub-regions by measuring sparseness and uniqueness of the responses evoked by specific paired-pulse stimuli. We used the evoked responses in CA3 to decode the stimulation sites in DG (and vice-versa) by means of learning algorithms for classification (support vector machine, SVM). The device was placed over an 8 × 8 grid of extracellular electrodes (micro-electrode array, MEA) in order to provide a platform for monitoring development, self-organization, and improved access to stimulation and recording at multiple sites. The micro-tunnels were designed with dimensions 3 × 10 × 400 μm allowing axonal growth but not migration of cell bodies and long enough to exclude traversal by dendrites. Paired-pulse stimulation (inter-pulse interval 50 ms) was applied at 22 different sites and repeated 25 times in each chamber for each sub-region to evoke time-locked activity. DG-DG and CA3-CA3 networks were used as controls. Stimulation in DG drove signals through the axons in the tunnels to activate a relatively small set of specific electrodes in CA3 (sparse code). CA3-CA3 and DG-DG controls were less sparse in coding than CA3 in DG-CA3 networks. Using all target electrodes with the three highest spike rates (14%), the evoked responses in CA3 specified each stimulation site in DG with optimum uniqueness of 64%. Finally, by SVM learning, these evoked responses in CA3 correctly decoded the stimulation sites in DG for 43% of the trials, significantly higher than the reverse, i.e., how well-recording in DG could predict the stimulation site in CA3. In conclusion, our co-cultured model for the in vivo DG-CA3 hippocampal network showed sparse and specific responses in CA3, selectively evoked by each stimulation site in DG. PMID:28321182

Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans.

PubMed

Oddo, Calogero Maria; Raspopovic, Stanisa; Artoni, Fiorenzo; Mazzoni, Alberto; Spigler, Giacomo; Petrini, Francesco; Giambattistelli, Federica; Vecchio, Fabrizio; Miraglia, Francesca; Zollo, Loredana; Di Pino, Giovanni; Camboni, Domenico; Carrozza, Maria Chiara; Guglielmelli, Eugenio; Rossini, Paolo Maria; Faraguna, Ugo; Micera, Silvestro

2016-03-08

Restoration of touch after hand amputation is a desirable feature of ideal prostheses. Here, we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction (MNT), which emulates to some extent the firing dynamics of SA1 cutaneous afferents. The MNT process was used to modulate the temporal pattern of electrical spikes delivered to the human median nerve via percutaneous microstimulation in four intact subjects and via implanted intrafascicular stimulation in one transradial amputee. Both approaches allowed the subjects to reliably discriminate spatial coarseness of surfaces as confirmed also by a hybrid neural model of the median nerve. Moreover, MNT-evoked EEG activity showed physiologically plausible responses that were superimposable in time and topography to the ones elicited by a natural mechanical tactile stimulation. These findings can open up novel opportunities for sensory restoration in the next generation of neuro-prosthetic hands.

Electrophysiological evidence for the antinociceptive effect of transcutaneous electrical stimulation on mechanically evoked responsiveness of dorsal horn neurons in neuropathic rats.

PubMed

Leem, J W; Park, E S; Paik, K S

1995-06-16

Using a rat model of peripheral neuropathy induced by a tight ligation of L5-6 spinal nerves, the effects of transcutaneous electrical stimulation on the mechanical responses of wide dynamic range (WDR) dorsal horn neurons were investigated. The responses of the WDR neurons to both the brush and pinch stimuli were found to be enhanced in the neuropathic rats compared to those in the normal rats. These enhanced responses were depressed by low-frequency and high-intensity transcutaneous electrical stimulation (2 Hz, 4-5 mA) applied to the somatic receptive field. The durations of the depressive effects on the brush responses ranged between 30 and 45 min and those on the pinch responses were 60-90 min. These results imply that the transcutaneous electrical stimulation used here produces an antinociceptive effect via a depressive action on the enhanced mechanical responsiveness of the spinal neurons in this rat model of peripheral neuropathy.

Passive motion reduces vestibular balance and perceptual responses

PubMed Central

Fitzpatrick, Richard C; Watson, Shaun R D

2015-01-01

With the hypothesis that vestibular sensitivity is regulated to deal with a range of environmental motion conditions, we explored the effects of passive whole-body motion on vestibular perceptual and balance responses. In 10 subjects, vestibular responses were measured before and after a period of imposed passive motion. Vestibulospinal balance reflexes during standing evoked by galvanic vestibular stimulation (GVS) were measured as shear reaction forces. Perceptual tests measured thresholds for detecting angular motion, perceptions of suprathreshold rotation and perceptions of GVS-evoked illusory rotation. The imposed conditioning motion was 10 min of stochastic yaw rotation (0.5–2.5 Hz ≤ 300 deg s−2) with subjects seated. This conditioning markedly reduced reflexive and perceptual responses. The medium latency galvanic reflex (300–350 ms) was halved in amplitude (48%; P = 0.011) but the short latency response was unaffected. Thresholds for detecting imposed rotation more than doubled (248%; P < 0.001) and remained elevated after 30 min. Over-estimation of whole-body rotation (30–180 deg every 5 s) before conditioning was significantly reduced (41.1 to 21.5%; P = 0.033). Conditioning reduced illusory vestibular sensations of rotation evoked by GVS (mean 113 deg for 10 s at 1 mA) by 44% (P < 0.01) and the effect persisted for at least 1 h (24% reduction; P < 0.05). We conclude that a system of vestibular sensory autoregulation exists and that this probably involves central and peripheral mechanisms, possibly through vestibular efferent regulation. We propose that failure of these regulatory mechanisms at different levels could lead to disorders of movement perception and balance control during standing. Key points Human activity exposes the vestibular organs to a wide dynamic range of motion. We aimed to discover whether the CNS regulates sensitivity to vestibular afference during exposure to ambient motion. Balance and perceptual responses to vestibular stimulation were measured before and after a 10 min period of imposed, moderate intensity, stochastic whole-body rotation. After this conditioning, vestibular balance reflexes evoked by galvanic vestibular stimulation were halved in amplitude. Conditioning doubled the thresholds for perceiving small rotations, and reduced perceptions of the amplitude of real rotations, and illusory rotation evoked by galvanic stimulation. We conclude that the CNS auto-regulates sensitivity to vestibular sensory afference and that this probably involves central and peripheral mechanisms, as might arise from vestibular efferent regulation. Failure of these regulatory mechanisms at different levels could lead to disorders of movement perception and balance control during standing. PMID:25809702

Auditory cortical activity after intracortical microstimulation and its role for sensory processing and learning.

PubMed

Deliano, Matthias; Scheich, Henning; Ohl, Frank W

2009-12-16

Several studies have shown that animals can learn to make specific use of intracortical microstimulation (ICMS) of sensory cortex within behavioral tasks. Here, we investigate how the focal, artificial activation by ICMS leads to a meaningful, behaviorally interpretable signal. In natural learning, this involves large-scale activity patterns in widespread brain-networks. We therefore trained gerbils to discriminate closely neighboring ICMS sites within primary auditory cortex producing evoked responses largely overlapping in space. In parallel, during training, we recorded electrocorticograms (ECoGs) at high spatial resolution. Applying a multivariate classification procedure, we identified late spatial patterns that emerged with discrimination learning from the ongoing poststimulus ECoG. These patterns contained information about the preceding conditioned stimulus, and were associated with a subsequent correct behavioral response by the animal. Thereby, relevant pattern information was mainly carried by neuron populations outside the range of the lateral spatial spread of ICMS-evoked cortical activation (approximately 1.2 mm). This demonstrates that the stimulated cortical area not only encoded information about the stimulation sites by its focal, stimulus-driven activation, but also provided meaningful signals in its ongoing activity related to the interpretation of ICMS learned by the animal. This involved the stimulated area as a whole, and apparently required large-scale integration in the brain. However, ICMS locally interfered with the ongoing cortical dynamics by suppressing pattern formation near the stimulation sites. The interaction between ICMS and ongoing cortical activity has several implications for the design of ICMS protocols and cortical neuroprostheses, since the meaningful interpretation of ICMS depends on this interaction.

Selective and graded recruitment of cat hamstring muscles with intrafascicular stimulation.

PubMed

Dowden, Brett R; Wilder, Andrew M; Hiatt, Scott D; Normann, Richard A; Brown, Nicholas A T; Clark, Gregory A

2009-12-01

The muscles of the hamstring group can produce different combinations of hip and knee torque. Thus, the ability to activate the different hamstring muscles selectively is of particular importance in eliciting functional movements such as stance and gait in a person with spinal cord injury. We investigated the ability of intrafascicular stimulation of the muscular branch of the sciatic nerve to recruit the feline hamstring muscles in a selective and graded fashion. A Utah Slanted Electrode Array, consisting of 100 penetrating microelectrodes, was implanted into the muscular branch of the sciatic nerve in six cats. Muscle twitches were evoked in the three compartments of biceps femoris (anterior, middle, and posterior), as well as semitendinosus and semimembranosus, using pulse-width modulated constant-voltage pulses. The resultant compound muscle action potentials were recorded using intramuscular fine-wire electrodes. 74% of the electrodes per implant were able to evoke a threshold response in these muscles, and these electrodes were evenly distributed among the instrumented muscles. Of the five muscles instrumented, on average 2.5 could be selectively activated to 90% of maximum EMG, and 3.5 could be selectively activated to 50% of maximum EMG. The muscles were recruited selectively with a mean stimulus dynamic range of 4.14 +/- 5.05 dB between threshold and either spillover to another muscle or a plateau in the response. This selective and graded activation afforded by intrafascicular stimulation of the muscular branch of the sciatic nerve suggests that it is a potentially useful stimulation paradigm for eliciting distinct forces in the hamstring muscle group in motor neuroprosthetic applications.

Bilateral somatosensory evoked potentials following intermittent theta-burst repetitive transcranial magnetic stimulation.

PubMed

Premji, Azra; Ziluk, Angela; Nelson, Aimee J

2010-08-05

Intermittent theta-burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation that may alter cortical excitability in the primary somatosensory cortex (SI). The present study investigated the effects of iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs) recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS. Compared to pre-iTBS, the amplitude of cortical potential N20/P25 was significantly increased for 5 minutes from non-stimulated SI and for 15 to 25 minutes from stimulated SI. Subcortical potentials recorded bilaterally remained unaltered following iTBS. We conclude that iTBS increases the cortical excitability of SI bilaterally and does not alter thalamocortical afferent input to SI. ITBS may provide one avenue to induce cortical plasticity in the somatosensory cortex.

Calcium Dynamics in Basal Dendrites of Layer 5A and 5B Pyramidal Neurons Is Tuned to the Cell-Type Specific Physiological Action Potential Discharge

PubMed Central

Krieger, Patrik; de Kock, Christiaan P. J.; Frick, Andreas

2017-01-01

Layer 5 (L5) is a major neocortical output layer containing L5A slender-tufted (L5A-st) and L5B thick-tufted (L5B-tt) pyramidal neurons. These neuron types differ in their in vivo firing patterns, connectivity and dendritic morphology amongst other features, reflecting their specific functional role within the neocortical circuits. Here, we asked whether the active properties of the basal dendrites that receive the great majority of synaptic inputs within L5 differ between these two pyramidal neuron classes. To quantify their active properties, we measured the efficacy with which action potential (AP) firing patterns backpropagate along the basal dendrites by measuring the accompanying calcium transients using two-photon laser scanning microscopy in rat somatosensory cortex slices. For these measurements we used both “artificial” three-AP patterns and more complex physiological AP patterns that were previously recorded in anesthetized rats in L5A-st and L5B-tt neurons in response to whisker stimulation. We show that AP patterns with relatively few APs (3APs) evoke a calcium response in L5B-tt, but not L5A-st, that is dependent on the temporal pattern of the three APs. With more complex in vivo recorded AP patterns, the average calcium response was similar in the proximal dendrites but with a decay along dendrites (measured up to 100 μm) of L5B-tt but not L5A-st neurons. Interestingly however, the whisker evoked AP patterns—although very different for the two cell types—evoke similar calcium responses. In conclusion, although the effectiveness with which different AP patterns evoke calcium transients vary between L5A-st and L5B-tt cell, the calcium influx appears to be tuned such that whisker-evoked calcium transients are within the same dynamic range for both cell types. PMID:28744201

Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation.

PubMed

Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D

2012-06-01

Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Counterbalanced, crossover study. Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. INTERVENTIONS/OUTCOMES: We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) > 0.2). Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. Wiley Periodicals, Inc.

Membrane potential correlates of sensory perception in mouse barrel cortex.

PubMed

Sachidhanandam, Shankar; Sreenivasan, Varun; Kyriakatos, Alexandros; Kremer, Yves; Petersen, Carl C H

2013-11-01

Neocortical activity can evoke sensory percepts, but the cellular mechanisms remain poorly understood. We trained mice to detect single brief whisker stimuli and report perceived stimuli by licking to obtain a reward. Pharmacological inactivation and optogenetic stimulation demonstrated a causal role for the primary somatosensory barrel cortex. Whole-cell recordings from barrel cortex neurons revealed membrane potential correlates of sensory perception. Sensory responses depended strongly on prestimulus cortical state, but both slow-wave and desynchronized cortical states were compatible with task performance. Whisker deflection evoked an early (<50 ms) reliable sensory response that was encoded through cell-specific reversal potentials. A secondary late (50-400 ms) depolarization was enhanced on hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation. Our data reveal dynamic processing in the sensory cortex during task performance, with an early sensory response reliably encoding the stimulus and later secondary activity contributing to driving the subjective percept.

Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns

PubMed Central

Cruchet, Steeve; Gustafson, Kyle; Benton, Richard; Floreano, Dario

2015-01-01

The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs—locomotor bouts—matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior. PMID:26600381

Neuroimaging and cognitive changes during déjà vu.

PubMed

Kovacs, Norbert; Auer, Tibor; Balas, Istvan; Karadi, Kazmer; Zambo, Katalin; Schwarcz, Attila; Klivenyi, Peter; Jokeit, Hennric; Horvath, Krisztina; Nagy, Ferenc; Janszky, Jozsef

2009-01-01

The cause or the physiological role of déjà vu (DV) in healthy people is unknown. The pathophysiology of DV-type epileptic aura is also unresolved. Here we describe a 22-year-old woman treated with deep brain stimulation (DBS) of the left internal globus pallidus for hemidystonia. At certain stimulation settings, DBS elicited reproducible episodes of DV. Neuropsychological tests and single-photon-emission computed tomography (SPECT) were performed during DBS-evoked DV and during normal DBS stimulation without DV. SPECT during DBS-evoked DV revealed hyperperfusion of the right (contralateral to the electrode) hippocampus and other limbic structures. Neuropsychological examinations performed during several evoked DV episodes revealed disturbances in nonverbal memory. Our results confirm the role of mesiotemporal structures in the pathogenesis of DV. We hypothesize that individual neuroanatomy and disturbances in gamma oscillations or in the dopaminergic system played a role in DBS-elicited DV in our patient.

Functional connectivity between right and left mesial temporal structures.

PubMed

Lacuey, Nuria; Zonjy, Bilal; Kahriman, Emine S; Kaffashi, Farhad; Miller, Jonathan; Lüders, Hans O

2015-09-01

The aim of this study is to investigate functional connectivity between right and left mesial temporal structures using cerebrocerebral evoked potentials. We studied seven patients with drug-resistant focal epilepsy who were explored with stereotactically implanted depth electrodes in bilateral hippocampi. In all patients cerebrocerebral evoked potentials evoked by stimulation of the fornix were evaluated as part of a research project assessing fornix stimulation for control of hippocampal seizures. Stimulation of the fornix elicited responses in the ipsilateral hippocampus in all patients with a mean latency of 4.6 ms (range 2-7 ms). Two patients (29 %) also had contralateral hippocampus responses with a mean latency of 7.5 ms (range 5-12 ms) and without involvement of the contralateral temporal neocortex or amygdala. This study confirms the existence of connections between bilateral mesial temporal structures in some patients and explains seizure discharge spreading between homotopic mesial temporal structures without neocortical involvement.

Functional MRI Detection of Hemodynamic Response of Repeated Median Nerve Stimulation

PubMed Central

Ai, Leo; Oya, Hiroyuki; Howard, Matthew; Xiong, Jinhu

2012-01-01

Median nerve stimulation is a commonly used technique in the clinical setting to determine areas of neuronal function in the brain. Neuronal activity of repeated median nerve stimulation is well studied. The cerebral hemodynamic response of the stimulation, on the other hand, is not very clear. In this study, we investigate how cerebral hemodynamics behaves over time using the same repeated median nerve stimulation. Ten subjects received constant repeated electrical stimulation to the right median nerve. Each subject had fMRI scans while receiving said stimulations for seven runs. Our results show that the BOLD signal significantly decreases across each run. Significant BOLD signal decreases can also be seen within runs. These results are consistent with studies that have studied the hemodynamic habituation effect with other forms of stimulation. However, the results do not completely agree with the findings of studies where evoked potentials were examined. Thus, further inquiry of how evoked potentials and cerebral hemodynamics are coupled when using constant stimulations is needed. PMID:23228312

Radiant energy required for infrared neural stimulation

DOE PAGES

Tan, Xiaodong; Rajguru, Suhrud; Young, Hunter; ...

2015-08-25

Infrared neural stimulation (INS) has been proposed as an alternative method to electrical stimulation because of its spatial selective stimulation. Independent of the mechanism for INS, to translate the method into a device it is important to determine the energy for stimulation required at the target structure. Custom-designed, flat and angle polished fibers, were used to deliver the photons. By rotating the angle polished fibers, the orientation of the radiation beam in the cochlea could be changed. INS-evoked compound action potentials and single unit responses in the central nucleus of the inferior colliculus (ICC) were recorded. X-ray computed tomography wasmore » used to determine the orientation of the optical fiber. Maximum responses were observed when the radiation beam was directed towards the spiral ganglion neurons (SGNs), whereas little responses were seen when the beam was directed towards the basilar membrane. The radiant exposure required at the SGNs to evoke compound action potentials (CAPs) or ICC responses was on average 18.9 ± 12.2 or 10.3 ± 4.9 mJ/cm 2, respectively. For cochlear INS it has been debated whether the radiation directly stimulates the SGNs or evokes a photoacoustic effect. The results support the view that a direct interaction between neurons and radiation dominates the response to INS.« less

Efficient and reliable characterization of the corticospinal system using transcranial magnetic stimulation.

PubMed

Kukke, Sahana N; Paine, Rainer W; Chao, Chi-Chao; de Campos, Ana C; Hallett, Mark

2014-06-01

The purpose of this study is to develop a method to reliably characterize multiple features of the corticospinal system in a more efficient manner than typically done in transcranial magnetic stimulation studies. Forty transcranial magnetic stimulation pulses of varying intensity were given over the first dorsal interosseous motor hot spot in 10 healthy adults. The first dorsal interosseous motor-evoked potential size was recorded during rest and activation to create recruitment curves. The Boltzmann sigmoidal function was fit to the data, and parameters relating to maximal motor-evoked potential size, curve slope, and stimulus intensity leading to half-maximal motor-evoked potential size were computed from the curve fit. Good to excellent test-retest reliability was found for all corticospinal parameters at rest and during activation with 40 transcranial magnetic stimulation pulses. Through the use of curve fitting, important features of the corticospinal system can be determined with fewer stimuli than typically used for the same information. Determining the recruitment curve provides a basis to understand the state of the corticospinal system and select subject-specific parameters for transcranial magnetic stimulation testing quickly and without unnecessary exposure to magnetic stimulation. This method can be useful in individuals who have difficulty in maintaining stillness, including children and patients with motor disorders.

Radiant energy required for infrared neural stimulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Xiaodong; Rajguru, Suhrud; Young, Hunter

Infrared neural stimulation (INS) has been proposed as an alternative method to electrical stimulation because of its spatial selective stimulation. Independent of the mechanism for INS, to translate the method into a device it is important to determine the energy for stimulation required at the target structure. Custom-designed, flat and angle polished fibers, were used to deliver the photons. By rotating the angle polished fibers, the orientation of the radiation beam in the cochlea could be changed. INS-evoked compound action potentials and single unit responses in the central nucleus of the inferior colliculus (ICC) were recorded. X-ray computed tomography wasmore » used to determine the orientation of the optical fiber. Maximum responses were observed when the radiation beam was directed towards the spiral ganglion neurons (SGNs), whereas little responses were seen when the beam was directed towards the basilar membrane. The radiant exposure required at the SGNs to evoke compound action potentials (CAPs) or ICC responses was on average 18.9 ± 12.2 or 10.3 ± 4.9 mJ/cm 2, respectively. For cochlear INS it has been debated whether the radiation directly stimulates the SGNs or evokes a photoacoustic effect. The results support the view that a direct interaction between neurons and radiation dominates the response to INS.« less

On the single sweep processing of auditory brainstem responses: click vs. chirp stimulations and active vs. passive electrodes.

PubMed

Corona-Strauss, Farah I; Delb, Wolfgang; Bloching, Marc; Strauss, Daniel J

2008-01-01

We have recently shown that click evoked auditory brainstem responses (ABRs) single sweeps can efficiently be processed by a hybrid novelty detection system. This approach allowed for the objective detection of hearing thresholds in a fraction of time of conventional schemes, making it appropriate for the efficient implementation of newborn hearing screening procedures. It is the objective of this study to evaluate whether this approach might further be improved by different stimulation paradigms and electrode settings. In particular, we evaluate chirp stimulations which compensate the basilar-membrane dispersion and active electrodes which are less sensitive to movements. This is the first study which is directed to a single sweep processing of chirp evoked ABRs. By concentrating on transparent features and a minimum number of adjustable parameters, we present an objective comparison of click vs.chirp stimulations and active vs. passive electrodes in the ultrafast ABR detection. We show that chirp evoked brainstem responses and active electrodes might improve the single sweeps analysis of ABRs.Consequently, we conclude that a single sweep processing of ABRs for the objective determination of hearing thresholds can further be improved by the use of optimized chirp stimulations and active electrodes.

The steady-state visual evoked potential in vision research: A review

PubMed Central

Norcia, Anthony M.; Appelbaum, L. Gregory; Ales, Justin M.; Cottereau, Benoit R.; Rossion, Bruno

2015-01-01

Periodic visual stimulation and analysis of the resulting steady-state visual evoked potentials were first introduced over 80 years ago as a means to study visual sensation and perception. From the first single-channel recording of responses to modulated light to the present use of sophisticated digital displays composed of complex visual stimuli and high-density recording arrays, steady-state methods have been applied in a broad range of scientific and applied settings.The purpose of this article is to describe the fundamental stimulation paradigms for steady-state visual evoked potentials and to illustrate these principles through research findings across a range of applications in vision science. PMID:26024451

MSG-Evoked c-Fos Activity in the Nucleus of the Solitary Tract Is Dependent upon Fluid Delivery and Stimulation Parameters

PubMed Central

Thompson, John A.

2016-01-01

The marker of neuronal activation, c-Fos, can be used to visualize spatial patterns of neural activity in response to taste stimulation. Because animals will not voluntarily consume aversive tastes, these stimuli are infused directly into the oral cavity via intraoral cannulae, whereas appetitive stimuli are given in drinking bottles. Differences in these 2 methods make comparison of taste-evoked brain activity between results that utilize these methods problematic. Surprisingly, the intraoral cannulae experimental conditions that produce a similar pattern of c-Fos activity in response to taste stimulation remain unexplored. Stimulation pattern (e.g., constant/intermittent) and hydration state (e.g., water-restricted/hydrated) are the 2 primary differences between delivering tastes via bottles versus intraoral cannulae. Thus, we quantified monosodium glutamate (MSG)-evoked brain activity, as measured by c-Fos, in the nucleus of the solitary tract (nTS; primary taste nucleus) across several conditions. The number and pattern of c-Fos neurons in the nTS of animals that were water-restricted and received a constant infusion of MSG via intraoral cannula most closely mimicked animals that consumed MSG from a bottle. Therefore, in order to compare c-Fos activity between cannulae-stimulated and bottle-stimulated animals, cannulated animals should be water restricted prior to stimulation, and receive taste stimuli at a constant flow. PMID:26762887

The development of cortico-motoneuronal projections investigated using magnetic brain stimulation in the infant macaque.

PubMed

Flament, D; Hall, E J; Lemon, R N

1992-02-01

1. The effects of magnetic brain stimulation on electromyographic (EMG) activity recorded from arm and hand muscles have been investigated in five infant and six adult macaque monkeys under ketamine sedation. 2. In the adults, brief, short-latency EMG responses could be readily evoked with magnetic stimuli of 40-50% of the maximum stimulator output (1.5 T). 3. In a cross-sectional study of five infant macaques, it was difficult to evoke EMG responses in young infants (less than 5 months old). Clear short-latency responses were first evoked in an animal 5.75 months old. This change was accompanied by an increase in the probability of occurrence of the responses. 4. In a longitudinal study of two infant monkeys over a period ranging from 2.5 to 14.5 months of age we found that clear short-latency responses were first evoked at 4 and at 5.5 months, respectively. In both animals there was a steady fall in response threshold which reached the adult range at 6.5 and 8 months, respectively. EMG responses in animals older than 8 months were indistinguishable from those in adults. 5. In the longitudinal study we also noted that the latency of EMG responses to magnetic brain stimulation declined with age. Since there were no comparable changes in the peripheral conduction time in these animals, we attribute this result to a decrease in central conduction time. 6. Parallel behavioural observations of the natural behaviour of the same animals within a colony indicated that mature precision movements of the fingers were not used until 5-6 months of age. 7. In two adult monkeys, the latency of EMG responses evoked in the extensor digitorum and first dorsal interosseous muscles by direct stimulation of the corticospinal tract, via electrodes implanted in the medullary pyramids, was found to be 0.7-1.7 ms shorter than that of responses evoked by magnetic stimuli. It is argued that at least the earliest component of these latter responses is conducted over the cortico-motoneuronal pathway. 8. The mechanisms likely to contribute to the late appearance of EMG responses to brain stimulation are discussed. One of these is probably the establishment of mature cortico-motoneuronal connections, which are not present at birth.

Diving Response in Rats: Role of the Subthalamic Vasodilator Area

PubMed Central

Golanov, Eugene V.; Shiflett, James M.; Britz, Gavin W.

2016-01-01

Diving response (DR) is a powerful integrative response targeted toward survival of the hypoxic/anoxic conditions. Being present in all animals and humans, it allows to survive adverse conditions like diving. Earlier, we discovered that forehead stimulation affords neuroprotective effect, decreasing infarction volume triggered by permanent occlusion of the middle cerebral artery in rats. We hypothesized that cold stimulation of the forehead induces DR in rats, which, in turn, exerts neuroprotection. We compared autonomic [AP, heart rate (HR), cerebral blood flow (CBF)] and EEG responses to the known DR-triggering stimulus, ammonia stimulation of the nasal mucosa, cold stimulation of the forehead, and cold stimulation of the glabrous skin of the tail base in anesthetized rats. Responses in AP, HR, CBF, and EEG to cold stimulation of the forehead and ammonia vapors instillation into the nasal cavity were comparable and differed significantly from responses to the cold stimulation of the tail base. Excitotoxic lesion of the subthalamic vasodilator area (SVA), which is known to participate in CBF regulation and to afford neuroprotection upon excitation, failed to affect autonomic components of the DR evoked by forehead cold stimulation or nasal mucosa ammonia stimulation. We conclude that cold stimulation of the forehead triggers physiological response comparable to the response evoked by ammonia vapor instillation into nasal cavity, which is considered as stimulus triggering protective DR. These observations may explain the neuroprotective effect of the forehead stimulation. Data demonstrate that SVA does not directly participate in the autonomic adjustments accompanying DR; however, it is involved in diving-evoked modulation of EEG. We suggest that forehead stimulation can be employed as a stimulus capable of triggering oxygen-conserving DR and can be used for neuroprotective therapy. PMID:27708614

Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission: implications for dopamine dysregulation disorders.

PubMed

Tye, S J; Miller, A D; Blaha, C D

2013-11-12

Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chronoamperometry and fixed potential amperometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 μg/μl) or N-methyl-d-aspartic acid (NMDA; 2 μg/μl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 μg/μl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 μg/μl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

SEPs to finger joint input lack the N20-P20 response that is evoked by tactile inputs: contrast between cortical generators in areas 3b and 2 in humans.

PubMed

Desmedt, J E; Ozaki, I

1991-01-01

A method using a DC servo motor is described to produce brisk angular movements at finger interphalangeal joints in humans. Small passive flexions of 2 degrees elicited sizable somatosensory evoked potentials (SEPs) starting with a contralateral positive P34 parietal response thought to reflect activation of a radial equivalent dipole generator in area 2 which receives joint inputs. By contrast, electric stimulation of tactile (non-joint) inputs from the distal phalanx evoked the usual contralateral negative N20 reflecting a tangential equivalent dipole generator in area 3b. Finger joint inputs also evoked a precentral positivity equivalent to the P22 of motor area 4, and a large frontal negativity equivalent to N30. It is suggested that natural stimulation allows human SEP components to be differentiated in conjunction with distinct cortical somatotopic projections.

Reduction hybrid artifacts of EMG-EOG in electroencephalography evoked by prefrontal transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Bai, Yang; Wan, Xiaohong; Zeng, Ke; Ni, Yinmei; Qiu, Lirong; Li, Xiaoli

2016-12-01

Objective. When prefrontal-transcranial magnetic stimulation (p-TMS) performed, it may evoke hybrid artifact mixed with muscle activity and blink activity in EEG recordings. Reducing this kind of hybrid artifact challenges the traditional preprocessing methods. We aim to explore method for the p-TMS evoked hybrid artifact removal. Approach. We propose a novel method used as independent component analysis (ICA) post processing to reduce the p-TMS evoked hybrid artifact. Ensemble empirical mode decomposition (EEMD) was used to decompose signal into multi-components, then the components were separated with artifact reduced by blind source separation (BSS) method. Three standard BSS methods, ICA, independent vector analysis, and canonical correlation analysis (CCA) were tested. Main results. Synthetic results showed that EEMD-CCA outperformed others as ICA post processing step in hybrid artifacts reduction. Its superiority was clearer when signal to noise ratio (SNR) was lower. In application to real experiment, SNR can be significantly increased and the p-TMS evoked potential could be recovered from hybrid artifact contaminated signal. Our proposed method can effectively reduce the p-TMS evoked hybrid artifacts. Significance. Our proposed method may facilitate future prefrontal TMS-EEG researches.

Substance P release and neurokinin 1 receptor activation in the rat spinal cord increase with the firing frequency of C-fibers.

PubMed

Adelson, D; Lao, L; Zhang, G; Kim, W; Marvizón, J C G

2009-06-30

Both the firing frequency of primary afferents and neurokinin 1 receptor (NK1R) internalization in dorsal horn neurons increase with the intensity of noxious stimulus. Accordingly, we studied how the pattern of firing of primary afferent influences NK1R internalization. In rat spinal cord slices, electrical stimulation of the dorsal root evoked NK1R internalization in lamina I neurons by inducing substance P release from primary afferents. The stimulation frequency had pronounced effects on NK1R internalization, which increased up to 100 Hz and then diminished abruptly at 200 Hz. Peptidase inhibitors increased NK1R internalization at frequencies below 30 Hz, indicating that peptidases limit the access of substance P to the receptor at moderate firing rates. NK1R internalization increased with number of pulses at all frequencies, but maximal internalization was substantially lower at 1-10 Hz than at 30 Hz. Pulses organized into bursts produced the same NK1R internalization as sustained 30 Hz stimulation. To determine whether substance P release induced at high stimulation frequencies was from C-fibers, we recorded compound action potentials in the sciatic nerve of anesthetized rats. We observed substantial NK1R internalization when stimulating at intensities evoking a C-elevation, but not at intensities evoking only an Adelta-elevation. Each pulse in trains at frequencies up to 100 Hz evoked a C-elevation, demonstrating that C-fibers can follow these high frequencies. C-elevation amplitudes declined progressively with increasing stimulation frequency, which was likely caused by a combination of factors including temporal dispersion. In conclusion, the instantaneous firing frequency in C-fibers determines the amount of substance P released by noxious stimuli.

Substance P release and neurokinin 1 receptor activation in the rat spinal cord increases with the firing frequency of C-fibers

PubMed Central

Adelson, David; Lao, Lijun; Zhang, Guohua; Kim, Woojae; Marvizón, Juan Carlos G.

2009-01-01

Both the firing frequency of primary afferents and neurokinin 1 receptor (NK1R) internalization in dorsal horn neurons increase with the intensity of noxious stimulus. Accordingly, we studied how the pattern of firing of primary afferent influences NK1R internalization. In rat spinal cord slices, electrical stimulation of the dorsal root evoked NK1R internalization in lamina I neurons by inducing substance P release from primary afferents. The stimulation frequency had pronounced effects on NK1R internalization, which increased up to 100 Hz and then diminished abruptly at 200 Hz. Peptidase inhibitors increased NK1R internalization at frequencies below 30 Hz, indicating that peptidases limit the access of substance P to the receptor at moderate firing rates. NK1R internalization increased with number of pulses at all frequencies, but maximal internalization was substantially lower at 1–10 Hz than at 30 Hz. Pulses organized into bursts produced the same NK1R internalization as sustained 30 Hz stimulation. To determine whether substance P release induced at high stimulation frequencies was from C-fibers, we recorded compound action potentials in the sciatic nerve of anesthetized rats. We observed substantial NK1R internalization when stimulating at intensities evoking a C-elevation, but not at intensities evoking only an Aδ-elevation. Each pulse in trains at frequencies up to 100 Hz evoked a C-elevation, demonstrating that C-fibers can follow these high frequencies. C-elevation amplitudes declined progressively with increasing stimulation frequency, which was likely caused by a combination of factors including temporal dispersion. In conclusion, the instantaneous firing frequency in C-fibers determines the amount of substance P released by noxious stimuli. PMID:19336248

Neurons of the A5 region are required for the tachycardia evoked by electrical stimulation of the hypothalamic defence area in anaesthetized rats.

PubMed

López-González, M V; Díaz-Casares, A; Peinado-Aragonés, C A; Lara, J P; Barbancho, M A; Dawid-Milner, M S

2013-08-01

In order to assess the possible interactions between the pontine A5 region and the hypothalamic defence area (HDA), we have examined the pattern of double staining for c-Fos protein immunoreactivity (c-Fos-ir) and tyrosine hydroxylase, throughout the rostrocaudal extent of the A5 region in spontaneously breathing anaesthetized male Sprague-Dawley rats during electrical stimulation of the HDA. Activation of the HDA elicited a selective increase in c-Fos-ir with an ipsilateral predominance in catecholaminergic and non-catecholaminergic A5 somata (P < 0.001 in both cases). A second group of experiments was done to examine the importance of the A5 region in modulating the cardiorespiratory response evoked from the HDA. Cardiorespiratory changes were analysed in response to electrical stimulation of the HDA before and after ipsilateral microinjection of muscimol within the A5 region. Stimulation of the HDA evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (P < 0.001) due to a decrease in expiratory time (P < 0.01). The respiratory response was accompanied by a pressor response (P < 0.001) and tachycardia (P < 0.001). After muscimol microinjection within the A5 region, pressor and heart rate responses to HDA stimulation were reduced (P < 0.01 and P < 0.001, respectively). The respiratory response persisted unchanged. Finally, to confirm functional interactions between the HDA and the A5 region, extracellular recordings of putative A5 neurones were obtained during HDA stimulation. Seventy-five A5 cells were recorded, 35 of which were affected by the HDA (47%). These results indicate that neurones of the A5 region participate in the cardiovascular response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

Substance P is a functional neurotransmitter in the rat parotid gland.

PubMed

Gallacher, D V

1983-09-01

The technique of electrical field stimulation was employed to stimulate the intrinsic nerves of isolated rat parotid gland fragments. Responses to field stimulation were recorded as changes in enzyme secretion (amylase release), radiolabelled ion fluxes (86Rb efflux) and electrophysiological effects (changes in acinar cell membrane potential and input resistance). All effects of field stimulation were abolished by the neurotoxin, tetrodotoxin (TTX). Selective use of pharmacological antagonists revealed that both the sympathetic and parasympathetic nerves to this tissue were being excited by field stimulation. Importantly a significant component of the response to field stimulation persisted in the presence of combined autonomic receptor blockade by atropine, phentolamine and propranolol, i.e. due to release of a non-cholinergic, non-adrenergic neurotransmitter. The non-cholinergic, non-adrenergic neurotransmitter evoked amylase release, 86Rb efflux and electrophysiological effects seen as changes in acinar cell membrane potential and conductance, i.e. stimulus-permeability coupled. Two biologically active peptides, substance P (SP) and vasoactive intestinal polypeptide (VIP) were shown to evoke amylase release in the presence of combined autonomic blockade. VIP however did not evoke any increase in 86Rb efflux, i.e. not stimulus-permeability coupled. All the effects of the non-cholinergic, non-adrenergic transmitter were mimicked by substance P which evokes 86Rb efflux and electrophysiological effects in addition to amylase release. The non-cholinergic, non-adrenergic field stimulus effects on amylase release and 86Rb efflux were abolished or markedly attenuated in tissues which had been desensitized by prior exposure to exogenous substance P. In the presence of VIP, however, the non-cholinergic, non-adrenergic effects persisted and were apparently potentiated. Acute application of the neurotoxin capsaicin first stimulated a transient release of amylase and subsequently abolished the non-cholinergic, non-adrenergic field stimulus-evoked enzyme release. The putative substance P antagonist, D-Pro2, D-Trp7,9 substance P, reversibly blocked the response to both non-cholinergic, non-adrenergic nerve stimulation and exogenous substance P. It was demonstrated however that prolonged exposure to this antagonist is associated with non-reversible and, importantly, non-specific neurotoxic effects. It is concluded that substance P or a closely related peptide is a functional neurotransmitter in the rat parotid gland.

Saturation in Phosphene Size with Increasing Current Levels Delivered to Human Visual Cortex.

PubMed

Bosking, William H; Sun, Ping; Ozker, Muge; Pei, Xiaomei; Foster, Brett L; Beauchamp, Michael S; Yoshor, Daniel

2017-07-26

Electrically stimulating early visual cortex results in a visual percept known as a phosphene. Although phosphenes can be evoked by a wide range of electrode sizes and current amplitudes, they are invariably described as small. To better understand this observation, we electrically stimulated 93 electrodes implanted in the visual cortex of 13 human subjects who reported phosphene size while stimulation current was varied. Phosphene size increased as the stimulation current was initially raised above threshold, but then rapidly reached saturation. Phosphene size also depended on the location of the stimulated site, with size increasing with distance from the foveal representation. We developed a model relating phosphene size to the amount of activated cortex and its location within the retinotopic map. First, a sigmoidal curve was used to predict the amount of activated cortex at a given current. Second, the amount of active cortex was converted to degrees of visual angle by multiplying by the inverse cortical magnification factor for that retinotopic location. This simple model accurately predicted phosphene size for a broad range of stimulation currents and cortical locations. The unexpected saturation in phosphene sizes suggests that the functional architecture of cerebral cortex may impose fundamental restrictions on the spread of artificially evoked activity and this may be an important consideration in the design of cortical prosthetic devices. SIGNIFICANCE STATEMENT Understanding the neural basis for phosphenes, the visual percepts created by electrical stimulation of visual cortex, is fundamental to the development of a visual cortical prosthetic. Our experiments in human subjects implanted with electrodes over visual cortex show that it is the activity of a large population of cells spread out across several millimeters of tissue that supports the perception of a phosphene. In addition, we describe an important feature of the production of phosphenes by electrical stimulation: phosphene size saturates at a relatively low current level. This finding implies that, with current methods, visual prosthetics will have a limited dynamic range available to control the production of spatial forms and that more advanced stimulation methods may be required. Copyright © 2017 the authors 0270-6474/17/377188-10$15.00/0.

Intralaminar stimulation of the inferior colliculus facilitates frequency-specific activation in the auditory cortex

NASA Astrophysics Data System (ADS)

Allitt, B. J.; Benjaminsen, C.; Morgan, S. J.; Paolini, A. G.

2013-08-01

Objective. Auditory midbrain implants (AMI) provide inadequate frequency discrimination for open set speech perception. AMIs that can take advantage of the tonotopic laminar of the midbrain may be able to better deliver frequency specific perception and lead to enhanced performance. Stimulation strategies that best elicit frequency specific activity need to be identified. This research examined the characteristic frequency (CF) relationship between regions of the auditory cortex (AC), in response to stimulated regions of the inferior colliculus (IC), comparing monopolar, and intralaminar bipolar electrical stimulation. Approach. Electrical stimulation using multi-channel micro-electrode arrays in the IC was used to elicit AC responses in anaesthetized male hooded Wistar rats. The rate of activity in AC regions with CFs within 3 kHz (CF-aligned) and unaligned CFs was used to assess the frequency specificity of responses. Main results. Both monopolar and bipolar IC stimulation led to CF-aligned neural activity in the AC. Altering the distance between the stimulation and reference electrodes in the IC led to changes in both threshold and dynamic range, with bipolar stimulation with 400 µm spacing evoking the lowest AC threshold and widest dynamic range. At saturation, bipolar stimulation elicited a significantly higher mean spike count in the AC at CF-aligned areas than at CF-unaligned areas when electrode spacing was 400 µm or less. Bipolar stimulation using electrode spacing of 400 µm or less also elicited a higher rate of elicited activity in the AC in both CF-aligned and CF-unaligned regions than monopolar stimulation. When electrodes were spaced 600 µm apart no benefit over monopolar stimulation was observed. Furthermore, monopolar stimulation of the external cortex of the IC resulted in more localized frequency responses than bipolar stimulation when stimulation and reference sites were 200 µm apart. Significance. These findings have implications for the future development of AMI, as a bipolar stimulation strategy may improve the ability of implant users to discriminate between frequencies.

Axono-cortical evoked potentials: A proof-of-concept study.

PubMed

Mandonnet, E; Dadoun, Y; Poisson, I; Madadaki, C; Froelich, S; Lozeron, P

2016-04-01

Awake surgery is currently considered the best method to tailor intraparenchymatous resections according to functional boundaries. However, the exact mechanisms by which electrical stimulation disturbs behavior remain largely unknown. In this case report, we describe a new method to explore the propagation toward cortical sites of a brief pulse applied to an eloquent white matter pathway. We present a patient, operated on in awake condition for removal of a cavernoma of the left ventral premotor cortex. At the end of the resection, the application of 60Hz stimulation in the white matter of the operculum induced anomia. Stimulating the same site at a frequency of 1Hz during 70seconds allowed to record responses on electrodes put over Broca's area and around the inferior part of central sulcus. Axono-cortical evoked potentials were then obtained by averaging unitary responses, time-locked to the stimulus. We then discuss the origin of these evoked axono-cortical potentials and the likely pathway connecting the stimulation site to the recorded cortical sites. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Prostaglandin E(2) stimulates glutamate receptor-dependent astrocyte neuromodulation in cultured hippocampal cells.

PubMed

Sanzgiri, R P; Araque, A; Haydon, P G

1999-11-05

Recent Ca(2+) imaging studies in cell culture and in situ have shown that Ca(2+) elevations in astrocytes stimulate glutamate release and increase neuronal Ca(2+) levels, and that this astrocyte-neuron signaling can be stimulated by prostaglandin E(2) (PGE(2)). We investigated the electrophysiological consequences of the PGE(2)-mediated astrocyte-neuron signaling using whole-cell recordings on cultured rat hippocampal cells. Focal application of PGE(2) to astrocytes evoked a Ca(2+) elevation in the stimulated cell by mobilizing internal Ca(2+) stores, which further propagated as a Ca(2+) wave to neighboring astrocytes. Whole-cell recordings from neurons revealed that PGE(2) evoked a slow inward current in neurons adjacent to astrocytes. This neuronal response required the presence of an astrocyte Ca(2+) wave and was mediated through both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. Taken together with previous studies, these data demonstrate that PGE(2)-evoked Ca(2+) elevations in astrocyte cause the release of glutamate which activates neuronal ionotropic receptors. Copyright 1999 John Wiley & Sons, Inc.

Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

NASA Astrophysics Data System (ADS)

Son, Taeyoon; Wang, Benquan; Lu, Yiming; Chen, Yanjun; Cao, Dingcai; Yao, Xincheng

2017-02-01

It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multimodal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

Motor output evoked by subsaccadic stimulation of primate frontal eye fields.

PubMed

Corneil, Brian D; Elsley, James K; Nagy, Benjamin; Cushing, Sharon L

2010-03-30

In addition to its role in shifting the line of sight, the oculomotor system is also involved in the covert orienting of visuospatial attention. Causal evidence supporting this premotor theory of attention, or oculomotor readiness hypothesis, comes from the effect of subsaccadic threshold stimulation of the oculomotor system on behavior and neural activity in the absence of evoked saccades, which parallels the effects of covert attention. Here, by recording neck-muscle activity from monkeys and systematically titrating the level of stimulation current delivered to the frontal eye fields (FEF), we show that such subsaccadic stimulation is not divorced from immediate motor output but instead evokes neck-muscle responses at latencies that approach the minimal conduction time to the motor periphery. On average, neck-muscle thresholds were approximately 25% lower than saccade thresholds, and this difference is larger for FEF sites associated with progressively larger saccades. Importantly, we commonly observed lower neck-muscle thresholds even at sites evoking saccades

Multiple-input single-output closed-loop isometric force control using asynchronous intrafascicular multi-electrode stimulation.

PubMed

Frankel, Mitchell A; Dowden, Brett R; Mathews, V John; Normann, Richard A; Clark, Gregory A; Meek, Sanford G

2011-06-01

Although asynchronous intrafascicular multi-electrode stimulation (IFMS) can evoke fatigue-resistant muscle force, a priori determination of the necessary stimulation parameters for precise force production is not possible. This paper presents a proportionally-modulated, multiple-input single-output (MISO) controller that was designed and experimentally validated for real-time, closed-loop force-feedback control of asynchronous IFMS. Experiments were conducted on anesthetized felines with a Utah Slanted Electrode Array implanted in the sciatic nerve, either acutely or chronically ( n = 1 for each). Isometric forces were evoked in plantar-flexor muscles, and target forces consisted of up to 7 min of step, sinusoidal, and more complex time-varying trajectories. The controller was successful in evoking steps in force with time-to-peak of less than 0.45 s, steady-state ripple of less than 7% of the mean steady-state force, and near-zero steady-state error even in the presence of muscle fatigue, but with transient overshoot of near 20%. The controller was also successful in evoking target sinusoidal and complex time-varying force trajectories with amplitude error of less than 0.5 N and time delay of approximately 300 ms. This MISO control strategy can potentially be used to develop closed-loop asynchronous IFMS controllers for a wide variety of multi-electrode stimulation applications to restore lost motor function.

The output per stimulus of acetylcholine from cerebral cortical slices in the presence or absence of cholinesterase inhibition

PubMed Central

Bourdois, P.S.; Mitchell, J.F.; Somogyi, G.T.; Szerb, J.C.

1974-01-01

1 The release of endogenous acetylcholine (ACh) from cerebral cortical slices stimulated at 0.25, 1, 4, 16 and 64 Hz was measured in the presence either of physostigmine or of physostigmine and atropine. 2 Atropine potentiated the evoked release of endogenous ACh especially at low frequencies resulting in an output per stimulus which sharply declined with increasing frequency of stimulation, while in the absence of atropine the output of ACh per stimulus was low and fairly constant. 3 The evoked release of [3H]-ACh per stimulus following the incubation of the slices with [3H]-choline, as estimated by means of rate constants of the evoked release of total radioactivity, showed a frequency dependence similar to endogenous ACh when the two were tested under identical conditions. 4 In the absence of an anticholinesterase the evoked release of [3H]-ACh per stimulus was dependent on frequency of stimulation in a similar way to that in the presence of physostigmine and atropine. 5 Results suggest that under physiological conditions, i.e. in the absence of an anti-cholinesterase, the release of ACh per stimulus decreases with increasing frequency of stimulation and that this decrease is due to a lag in the mobilization of stored ACh rather than in the synthesis of new ACh. PMID:4455327

Muscarinic inhibition of [3H]-noradrenaline release on rabbit iris in vitro: effects of stimulation conditions on intrinsic activity of methacholine and pilocarpine.

PubMed Central

Bognar, I. T.; Pallas, S.; Fuder, H.; Muscholl, E.

1988-01-01

1. Rabbit isolated irides were loaded with [3H]-noradrenaline and superfused with Tyrode solution. The inhibition by the muscarinic agonists (+/-)-methacholine and pilocarpine of the [3H]-noradrenaline overflow into the superfusate evoked by field stimulation (pulses of 1 ms duration, 75 mA) was measured as an index of activation of presynaptic muscarinic receptors. 2. The fractional rate of release per pulse during the first stimulation period (S1) was low with 360 pulses at 3 Hz, intermediate with 360 pulses at 10 Hz and high with 1200 pulses at 10 Hz. Upon repetitive stimulation (7 periods at 20 min intervals), the fractional rates of release per pulse during S7 no longer differed, suggesting a 'long-term' regulation of [3H]-noradrenaline release depending on the stimulation conditions. 3. The evoked [3H]-noradrenaline overflow was depressed by (+/-)-methacholine in a concentration-dependent manner. The EC50 ranged from 0.29 to 0.42 microM. Methacholine nearly abolished the transmitter release evoked at 3 Hz but reduced that induced at 10 Hz by only 50%. Under the latter condition the methacholine concentration-inhibition curve was bell-shaped and no muscarinic inhibition was observed in the presence of methacholine 30 microM. After washout of methacholine the evoked [3H]-noradrenaline release was temporarily enhanced. 4. Atropine 0.1 microM enhanced the [3H]-noradrenaline overflow (evoked by stimulation with 360 or 1200 pulses at 10 Hz), probably antagonizing a presynaptic inhibition by endogenous acetylcholine. The inhibition by methacholine was competitively antagonized by atropine 0.1 microM (apparent -log KB = 8.5-9.0). 5. Depending on the concentration, pilocarpine reduced the [3H]-noradrenaline overflow evoked by 360 pulses at 3 Hz up to 63%. However, at 10 Hz stimulation frequency the compound was inactive as an agonist but competitively antagonized the presynaptic inhibition induced by methacholine. The KB under the latter condition (0.95 microM) was very close to the EC50 value determined at 3 Hz (0.85 microM). 6. The results demonstrate a muscarinic inhibition of noradrenaline release from the rabbit isolated iris. The activation by pilocarpine of the presynaptic receptors provides an alternative explanation for the miosis induced in the rabbit in vivo, which might be the result of a decreased sympathetic tone in the iris dilator muscle. PMID:3052680

Olfactory Nerve–Evoked, Metabotropic Glutamate Receptor–Mediated Synaptic Responses in Rat Olfactory Bulb Mitral Cells

PubMed Central

Ennis, Matthew; Zhu, Mingyan; Heinbockel, Thomas; Hayar, Abdallah

2008-01-01

The group I metabotropic glutamate receptor (mGluR) subtype, mGluR1, is highly expressed on the apical dendrites of olfactory bulb mitral cells and thus may be activated by glutamate released from olfactory nerve (ON) terminals. Previous studies have shown that mGluR1 agonists directly excite mitral cells. In the present study, we investigated the involvement of mGluR1 in ON-evoked responses in mitral cells in rat olfactory bulb slices using patch-clamp electrophysiology. In voltage-clamp recordings, the average EPSC evoked by single ON shocks or brief trains of ON stimulation (six pulses at 50 Hz) in normal physiological conditions were not significantly affected by the nonselective mGluR antagonist LY341495 (50–100 μM) or the mGluR1-specific antagonist LY367385 (100 μM); ON-evoked responses were attenuated, however, in a subset (36%) of cells. In the presence of blockers of ionotropic glutamate and GABA receptors, application of the glutamate uptake inhibitors THA (300 μM) and TBOA (100 μM) revealed large-amplitude, long-duration responses to ON stimulation, whereas responses elicited by antidromic activation of mitral/tufted cells were unaffected. Magnitudes of the ON-evoked responses elicited in the presence of THA–TBOA were dependent on stimulation intensity and frequency, and were maximal during high-frequency (50-Hz) bursts of ON spikes, which occur during odor stimulation. ON-evoked responses elicited in the presence of THA–TBOA were significantly reduced or completely blocked by LY341495 or LY367385 (100 μM). These results demonstrate that glutamate transporters tightly regulate access of synaptically evoked glutamate from ON terminals to postsynaptic mGluR1s on mitral cell apical dendrites. Taken together with other findings, the present results suggest that mGluR1s may not play a major role in phasic responses to ON input, but instead may play an important role in shaping slow oscillatory activity in mitral cells and/or activity-dependent regulation of plasticity at ON–mitral cell synapses. PMID:16394070

Effective intracortical microstimulation parameters applied to primary motor cortex for evoking forelimb movements to stable spatial end points

PubMed Central

Van Acker, Gustaf M.; Amundsen, Sommer L.; Messamore, William G.; Zhang, Hongyu Y.; Luchies, Carl W.; Kovac, Anthony

2013-01-01

High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) applied to motor cortex is recognized as a useful and informative method for corticomotor mapping by evoking natural-appearing movements of the limb to consistent stable end-point positions. An important feature of these movements is that stimulation of a specific site in motor cortex evokes movement to the same spatial end point regardless of the starting position of the limb. The goal of this study was to delineate effective stimulus parameters for evoking forelimb movements to stable spatial end points from HFLD-ICMS applied to primary motor cortex (M1) in awake monkeys. We investigated stimulation of M1 as combinations of frequency (30–400 Hz), amplitude (30–200 μA), and duration (0.5–2 s) while concurrently recording electromyographic (EMG) activity from 24 forelimb muscles and movement kinematics with a motion capture system. Our results suggest a range of parameters (80–140 Hz, 80–140 μA, and 1,000-ms train duration) that are effective and safe for evoking forelimb translocation with subsequent stabilization at a spatial end point. The mean time for stimulation to elicit successful movement of the forelimb to a stable spatial end point was 475.8 ± 170.9 ms. Median successful frequency and amplitude were 110 Hz and 110 μA, respectively. Attenuated parameters resulted in inconsistent, truncated, or undetectable movements, while intensified parameters yielded no change to movement end points and increased potential for large-scale physiological spread and adverse focal motor effects. Establishing cortical stimulation parameters yielding consistent forelimb movements to stable spatial end points forms the basis for a systematic and comprehensive mapping of M1 in terms of evoked movements and associated muscle synergies. Additionally, the results increase our understanding of how the central nervous system may encode movement. PMID:23741044

Smooth pursuitlike eye movements evoked by microstimulation in macaque nucleus reticularis tegmenti pontis.

PubMed

Yamada, T; Suzuki, D A; Yee, R D

1996-11-01

1. Smooth pursuitlike eye movements were evoked with low current microstimulation delivered to rostral portions of the nucleus reticularis tegmenti pontis (rNRTP) in alert macaques. Microstimulation sites were selected by the observation of modulations in single-cell firing rates that were correlated with periodic smoothpursuit eye movements. Current intensities ranged from 10 to 120 microA and were routinely < 40 microA. Microstimulation was delivered either in the dark with no fixation, 100 ms after a fixation target was extinguished, or during maintained fixation of a stationary or moving target. Evoked eye movements also were studied under open-loop conditions with the target image stabilized on the retina. 2. Eye movements evoked in the absence of a target rapidly accelerated to a constant velocity that was maintained for the duration of the microstimulation. Evoked eye speeds ranged from 3.7 to 23 deg/s and averaged 11 deg/s. Evoked eye speed appeared to be linearly related to initial eye position with a sensitivity to initial eye position that averaged 0.23 deg.s-1.deg-1. While some horizontal and oblique smooth eye movements were elicited, microstimulation resulted in upward eye movements in 89% of the sites. 3. Evoked eye speed was found to be dependent on microstimulation pulse frequency and current intensity. Within limits, evoked eye speed increased with increases in stimulation frequency or current intensity. For stimulation frequencies < 300-400 Hz, only smooth pursuit-like eye movements were evoked. At higher stimulation frequencies, accompanying saccades consistently were elicited. 4. Feedback of retinal image motion interacted with the evoked eye movements to decrease eye speed if the visual motion was in the opposite direction as the evoked, pursuit-like eye movements. 5. The results implicate rNRTP as part of the neuronal substrate that controls smooth-pursuit eye movements. NRTP appears to be divided functionally into a rostral, pursuit-related portion and a caudal, saccade-related area. rNRTP is a component of a corticopontocerebellar circuit that presumably involves the pursuit area of the frontal eye field and that parallels the middle and medial superior temporal cerebral cortical/dorsalateral pontine nucleus (MT/MST-DLPN-cerebellum) pathway known to be involved also with regulating smooth-pursuit eye movements.

Electrical stimulation of dorsal root entry zone attenuates wide-dynamic range neuronal activity in rats

PubMed Central

Yang, Fei; Zhang, Chen; Xu, Qian; Tiwari, Vinod; He, Shao-Qiu; Wang, Yun; Dong, Xinzhong; Vera-Portocarrero, Louis P.; Wacnik, Paul W.; Raja, Srinivasa N.; Guan, Yun

2014-01-01

Objectives Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. Materials and Methods We conducted in vivo extracellular single-unit recordings of WDR neurons in rats after an L5 spinal nerve ligation (SNL) or sham surgery. We set bipolar electrical stimulation (50 Hz, 0.2 ms, 5 min) of the DREZ at the intensity that activated only Aα/β-fibers by measuring the lowest current at which DREZ stimulation evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ/C-compound action potential (i.e., Ab1). Results The elevated spontaneous activity rate of WDR neurons in SNL rats [n=25; data combined from day 14–16 (n = 15) and day 45–75 post-SNL groups (n=10)] was significantly decreased from the pre-stimulation level (p<0.01) at 0–15 min and 30–45 min post-stimulation. In both sham-operated (n=8) and nerve-injured rats, DREZ stimulation attenuated the C-component, but not A-component, of the WDR neuronal response to graded intracutaneous electrical stimuli (0.1–10 mA, 2 ms) applied to the skin receptive field. Further, DREZ stimulation blocked windup (a short form of neuronal sensitization) to repetitive noxious stimuli (0.5 Hz) at 0–15 min in all groups (p<0.05). Conclusions Attenuation of WDR neuronal activity may contribute to DREZ stimulation-induced analgesia. This finding supports the notion that DREZ may be a useful target for neuromodulatory control of pain. PMID:25308522

Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after Spinal Cord Injury

PubMed Central

Butler, Jane E.; Godfrey, Sharlene; Thomas, Christine K.

2016-01-01

Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury. PMID:27049521

β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum

PubMed Central

Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Xia, Yun; Zou, Fei; Qu, Meihua; Needleman, Bradley J.; Mikami, Dean J.

2015-01-01

Intracellular microelectrodes were used to record neurogenic inhibitory junction potentials in the intestinal circular muscle coat. Electrical field stimulation was used to stimulate intramural neurons and evoke contraction of the smooth musculature. Exposure to β-nicotinamide adenine dinucleotide (β-NAD) did not alter smooth muscle membrane potential in guinea pig colon or human jejunum. ATP, ADP, β-NAD, and adenosine, as well as the purinergic P2Y1 receptor antagonists MRS 2179 and MRS 2500 and the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine, each suppressed inhibitory junction potentials in guinea pig and human preparations. β-NAD suppressed contractile force of twitch-like contractions evoked by electrical field stimulation in guinea pig and human preparations. P2Y1 receptor antagonists did not reverse this action. Stimulation of adenosine A1 receptors with 2-chloro-N6-cyclopentyladenosine suppressed the force of twitch contractions evoked by electrical field stimulation in like manner to the action of β-NAD. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine suppressed the inhibitory action of β-NAD on the force of electrically evoked contractions. The results do not support an inhibitory neurotransmitter role for β-NAD at intestinal neuromuscular junctions. The data suggest that β-NAD is a ligand for the adenosine A1 receptor subtype expressed by neurons in the enteric nervous system. The influence of β-NAD on intestinal motility emerges from adenosine A1 receptor-mediated suppression of neurotransmitter release at inhibitory neuromuscular junctions. PMID:25813057

Deep Brain Stimulation of Heschl Gyrus: Implantation Technique, Intraoperative Localization, and Effects of Stimulation.

PubMed

Donovan, Chris; Sweet, Jennifer; Eccher, Matthew; Megerian, Cliff; Semaan, Maroun; Murray, Gail; Miller, Jonathan

2015-12-01

Tinnitus is a source of considerable morbidity, and neuromodulation has been shown to be a potential treatment option. However, the location of the primary auditory cortex within Heschl gyrus in the temporal operculum presents challenges for targeting and electrode implantation. To determine whether anatomic targeting with intraoperative verification using evoked potentials can be used to implant electrodes directly into the Heschl gyrus (HG). Nine patients undergoing stereo-electroencephalogram evaluation for epilepsy were enrolled. HG was directly targeted on volumetric magnetic resonance imaging, and framed stereotaxy was used to implant an electrode parallel to the axis of the gyrus by using an oblique anterolateral-posteromedial trajectory. Intraoperative evoked potentials from auditory stimuli were recorded from multiple electrode contacts. Postoperatively, stimulation of each electrode was performed and participants were asked to describe the percept. Audiometric analysis was performed for 2 participants during subthreshold stimulation. Sounds presented to the contralateral and ipsilateral ears produced evoked potentials in HG electrodes in all participants intraoperatively. Stimulation produced a reproducible sensation of sound in all participants with perceived volume proportional to amplitude. Four participants reported distinct sounds when different electrodes were stimulated, with more medial contacts producing tones perceived as higher in pitch. Stimulation was not associated with adverse audiometric effects. There were no complications of electrode implantation. Direct anatomic targeting with physiological verification can be used to implant electrodes directly into primary auditory cortex. If deep brain stimulation proves effective for intractable tinnitus, this technique may be useful to assist with electrode implantation. DBS, deep brain stimulatorEEG, electroencephalographyHG, Heschl gyrus.

Submillisecond unmasked subliminal visual stimuli evoke electrical brain responses.

PubMed

Sperdin, Holger F; Spierer, Lucas; Becker, Robert; Michel, Christoph M; Landis, Theodor

2015-04-01

Subliminal perception is strongly associated to the processing of meaningful or emotional information and has mostly been studied using visual masking. In this study, we used high density 256-channel EEG coupled with an liquid crystal display (LCD) tachistoscope to characterize the spatio-temporal dynamics of the brain response to visual checkerboard stimuli (Experiment 1) or blank stimuli (Experiment 2) presented without a mask for 1 ms (visible), 500 µs (partially visible), and 250 µs (subliminal) by applying time-wise, assumption-free nonparametric randomization statistics on the strength and on the topography of high-density scalp-recorded electric field. Stimulus visibility was assessed in a third separate behavioral experiment. Results revealed that unmasked checkerboards presented subliminally for 250 µs evoked weak but detectable visual evoked potential (VEP) responses. When the checkerboards were replaced by blank stimuli, there was no evidence for the presence of an evoked response anymore. Furthermore, the checkerboard VEPs were modulated topographically between 243 and 296 ms post-stimulus onset as a function of stimulus duration, indicative of the engagement of distinct configuration of active brain networks. A distributed electrical source analysis localized this modulation within the right superior parietal lobule near the precuneus. These results show the presence of a brain response to submillisecond unmasked subliminal visual stimuli independently of their emotional saliency or meaningfulness and opens an avenue for new investigations of subliminal stimulation without using visual masking. © 2014 Wiley Periodicals, Inc.

Acute dynamin inhibition dissects synaptic vesicle recycling pathways that drive spontaneous and evoked neurotransmission

PubMed Central

Chung, ChiHye; Barlyko, Barbara; Leitz, Jeremy; Liu, Xinran; Kavalali, Ege T.

2010-01-01

Synapses maintain synchronous, asynchronous and spontaneous forms of neurotransmission that are distinguished by their Ca2+-dependence and time course. Despite recent advances in our understanding of the mechanisms that underlie these three forms of release, it remains unclear whether they originate from the same vesicle population or arise from distinct vesicle pools with diverse propensities for release. Here, we used a reversible inhibitor of dynamin, dynasore, to dissect the vesicle pool dynamics underlying the three forms of neurotransmitter release in hippocampal GABAergic inhibitory synapses. In dynasore, evoked synchronous release and asynchronous neurotransmission detected after activity showed marked and unrecoverable depression within seconds. In contrast, spontaneous release remained intact after intense stimulation in dynasore or during prolonged (~1 hour) application of dynasore at rest, suggesting that separate recycling pathways maintain evoked and spontaneous synaptic vesicle trafficking. In addition, simultaneous imaging of spectrally separable styryl dyes revealed that in a given synapse vesicles that recycle spontaneously and in response to activity do not mix. These findings suggest that evoked synchronous and asynchronous release originate from the same vesicle pool that recycles rapidly in a dynamin-dependent manner, while a distinct vesicle pool sustains spontaneous release independent of dynamin activation. This result lends further support to the notion that synapses harbor distinct vesicle populations with divergent release properties that maintain independent forms of neurotransmission. PMID:20107062

Magnetothermal genetic deep brain stimulation of motor behaviors in awake, freely moving mice

PubMed Central

Zhang, Qian; Castellanos Rubio, Idoia; del Pino, Pablo

2017-01-01

Establishing how neurocircuit activation causes particular behaviors requires modulating the activity of specific neurons. Here, we demonstrate that magnetothermal genetic stimulation provides tetherless deep brain activation sufficient to evoke motor behavior in awake mice. The approach uses alternating magnetic fields to heat superparamagnetic nanoparticles on the neuronal membrane. Neurons, heat-sensitized by expressing TRPV1 are activated with magnetic field application. Magnetothermal genetic stimulation in the motor cortex evoked ambulation, deep brain stimulation in the striatum caused rotation around the body-axis, and stimulation near the ridge between ventral and dorsal striatum caused freezing-of-gait. The duration of the behavior correlated tightly with field application. This approach provides genetically and spatially targetable, repeatable and temporarily precise activation of deep-brain circuits without the need for surgical implantation of any device. PMID:28826470

Infrared neural stimulation (INS) inhibits electrically evoked neural responses in the deaf white cat

NASA Astrophysics Data System (ADS)

Richter, Claus-Peter; Rajguru, Suhrud M.; Robinson, Alan; Young, Hunter K.

2014-03-01

Infrared neural stimulation (INS) has been used in the past to evoke neural activity from hearing and partially deaf animals. All the responses were excitatory. In Aplysia californica, Duke and coworkers demonstrated that INS also inhibits neural responses [1], which similar observations were made in the vestibular system [2, 3]. In deaf white cats that have cochleae with largely reduced spiral ganglion neuron counts and a significant degeneration of the organ of Corti, no cochlear compound action potentials could be observed during INS alone. However, the combined electrical and optical stimulation demonstrated inhibitory responses during irradiation with infrared light.

Evaluating interhemispheric cortical responses to transcranial magnetic stimulation in chronic stroke: A TMS-EEG investigation.

PubMed

Borich, Michael R; Wheaton, Lewis A; Brodie, Sonia M; Lakhani, Bimal; Boyd, Lara A

2016-04-08

TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri-central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15-30Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition

PubMed Central

Duguid, Ian; Branco, Tiago; Chadderton, Paul; Arlt, Charlotte; Powell, Kate; Häusser, Michael

2015-01-01

Classical feed-forward inhibition involves an excitation–inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses. PMID:26432880

Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity.

PubMed

Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah

2014-11-01

More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1-12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n=12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n=39), where a subset (n=11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P=0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P=0.30). Experimental tactile (P=0.012) and noxious (P=0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity

PubMed Central

Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah

2014-01-01

More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1–12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n = 12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n = 39), where a subset (n = 11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P = 0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P = 0.30). Experimental tactile (P = 0.012) and noxious (P = 0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. PMID:25218826

Frames of reference for gaze saccades evoked during stimulation of lateral intraparietal cortex.

PubMed

Constantin, A G; Wang, H; Martinez-Trujillo, J C; Crawford, J D

2007-08-01

Previous studies suggest that stimulation of lateral intraparietal cortex (LIP) evokes saccadic eye movements toward eye- or head-fixed goals, whereas most single-unit studies suggest that LIP uses an eye-fixed frame with eye-position modulations. The goal of our study was to determine the reference frame for gaze shifts evoked during LIP stimulation in head-unrestrained monkeys. Two macaques (M1 and M2) were implanted with recording chambers over the right intraparietal sulcus and with search coils for recording three-dimensional eye and head movements. The LIP region was microstimulated using pulse trains of 300 Hz, 100-150 microA, and 200 ms. Eighty-five putative LIP sites in M1 and 194 putative sites in M2 were used in our quantitative analysis throughout this study. Average amplitude of the stimulation-evoked gaze shifts was 8.67 degrees for M1 and 7.97 degrees for M2 with very small head movements. When these gaze-shift trajectories were rotated into three coordinate frames (eye, head, and body), gaze endpoint distribution for all sites was most convergent to a common point when plotted in eye coordinates. Across all sites, the eye-centered model provided a significantly better fit compared with the head, body, or fixed-vector models (where the latter model signifies no modulation of the gaze trajectory as a function of initial gaze position). Moreover, the probability of evoking a gaze shift from any one particular position was modulated by the current gaze direction (independent of saccade direction). These results provide causal evidence that the motor commands from LIP encode gaze command in eye-fixed coordinates but are also subtly modulated by initial gaze position.

Prolonged deficits in parvalbumin neuron stimulation-evoked network activity despite recovery of dendritic structure and excitability in the somatosensory cortex following global ischemia in mice.

PubMed

Xie, Yicheng; Chen, Shangbin; Wu, Yujin; Murphy, Timothy H

2014-11-05

Relatively few studies have examined plasticity of inhibitory neuronal networks following stroke in vivo, primarily due to the inability to selectively monitor inhibition. We assessed the structure of parvalbumin (PV) interneurons during a 5 min period of global ischemia and reperfusion in mice, which mimicked cerebral ischemia during cardiac arrest or forms of transient ischemic attack. The dendritic structure of PV-neurons in cortical superficial layers was rapidly swollen and beaded during global ischemia, but recovered within 5-10 min following reperfusion. Using optogenetics and a multichannel optrode, we investigated the function of PV-neurons in mouse forelimb somatosensory cortex. We demonstrated pharmacologically that PV-channelrhodopsin-2 (ChR2) stimulation evoked activation in layer IV/V, which resulted in rapid current sinks mediated by photocurrent and action potentials (a measure of PV-neuron excitability), which was then followed by current sources mediated by network GABAergic synaptic activity. During ischemic depolarization, the PV-ChR2-evoked current sinks (excitability) were suppressed, but recovered rapidly following reperfusion concurrent with repolarization of the DC-EEG. In contrast, the current sources reflecting GABAergic synaptic network activity recovered slowly and incompletely, and was coincident with the partial recovery of the forepaw stimulation-evoked current sinks in layer IV/V 30 min post reperfusion. Our in vivo data suggest that the excitability of PV inhibitory neurons was suppressed during global ischemia and rapidly recovered during reperfusion. In contrast, PV-ChR2 stimulation-evoked GABAergic synaptic network activity exhibited a prolonged suppression even ∼1 h after reperfusion, which could contribute to the dysfunction of sensation and cognition following transient global ischemia. Copyright © 2014 the authors 0270-6474/14/3414890-12$15.00/0.

Augmenting responses evoked in area 17 of the cat by intracortical axon collaterals of cortico-geniculate cells.

PubMed Central

Ferster, D; Lindström, S

1985-01-01

Evoked potentials were recorded in the visual cortex of the cat after electrical stimulation of the lateral geniculate nucleus (l.g.n.). The primary response, mediated by geniculo-cortical fibres, was depressed at stimulation frequencies above 7 Hz and replaced by a late potential, the incremental response, which gradually increased in amplitude with successive stimuli. The incremental response was a negative-positive potential in the depth of the cortex with the negative component having maximal amplitude in layer 4. The response reversed polarity in layer 1 to become a positive-negative potential at the surface. The latency of the negative component of the incremental response was about 3.5-4 ms in layer 4, compared to about 1.5 and 2.5 ms for the mono- and disynaptic components of the primary response. The incremental response could only be evoked from the l.g.n. and the optic radiation, not from the optic tract, superior colliculus or other surrounding structures. Within the l.g.n., the effect was only evoked from stimulation sites in approximate retinotopic register with the recording site in the cortex. Low threshold points were found in the A laminae, completely overlapping with the low threshold points for the primary response. Thresholds increased steeply when the stimulation electrode was lowered into the C laminae. The incremental response could still be evoked ten days after the destruction of all cells in the l.g.n. complex by kainic acid. It is concluded that the described incremental response is identical to the augmenting response of Dempsey & Morison (1943) and is mediated by intracortical axon collaterals of antidromically activated cortico-geniculate neurones. Images Plate 1 PMID:4057097

Presynaptic control of transmission along the pathway mediating disynaptic reciprocal inhibition in the cat

PubMed Central

Enríquez-Denton, M; Nielsen, J; Perreault, M-C; Morita, H; Petersen, N; Hultborn, H

2000-01-01

In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. Conditioning stimulation of flexor, but not ankle extensor, nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This depression lasted between 200 and 700 ms and was not accompanied by a depression of the monosynaptic EPSPs evoked by stimulation of descending pathways. These results suggest that flexor, but not ankle extensor, group I afferent fibres can modulate sensory transmission at the synapse between Ia afferent fibres and Ia inhibitory interneurones. Conditioning stimulation of flexor muscle nerves, extensor muscle nerves and cutaneous nerves produced a long-lasting increase in excitability of the terminals of the Ia inhibitory interneurones. The increase in the excitability of the terminals was not secondary to an electrotonic spread of synaptic excitation at the soma. Indeed, concomitant with the excitability increase of the terminals there were signs of synaptic inhibition in the soma. The unitary IPSPs induced in target motoneurones following the spike activity of single Ia inhibitory interneurones were depressed by conditioning stimulation of muscle and cutaneous nerves. Since the conditioning stimulation also evoked compound IPSPs in those motoneurones, a firm conclusion as to whether unitary IPSP depression involved presynaptic inhibitory mechanism of the terminals of the interneurones could not be reached. The possibility that the changes in excitability of the Ia interneuronal terminals reflect the presence of a presynaptic inhibitory mechanism similar to that operating at the terminals of the afferent fibres (presynaptic inhibition) is discussed.1. In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. PMID:10922013

Video-signal synchronizes registration of visual evoked responses.

PubMed

Vít, F; Kuba, M; Kremlácek, J; Kubová, Z; Horevaj, M

1996-01-01

Autodesk Animator software offers the suitable technique for visual stimulation in the registration of visual evoked responses (VERs). However, it is not possible to generate pulses that are synchronous with the animated sequences on any output port of the computer. These pulses are necessary for the synchronization of the computer that makes the registration of the VERs. The principle of the circuit is presented that is able to provide the synchronization of the analyzer with the stimulation computer using Autodesk Animator software.

Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery.

PubMed

Shigematsu, Hideki; Kawaguchi, Masahiko; Hayashi, Hironobu; Takatani, Tsunenori; Iwata, Eiichiro; Tanaka, Masato; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Tanaka, Yuu; Tanaka, Yasuhito

2017-10-01

During spine surgery, the spinal cord is electrophysiologically monitored via transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) to prevent injury. Transcranial electrical stimulation of motor-evoked potential involves the use of either constant-current or constant-voltage stimulation; however, there are few comparative data available regarding their ability to adequately elicit compound motor action potentials. We hypothesized that the success rates of TES-MEP recordings would be similar between constant-current and constant-voltage stimulations in patients undergoing spine surgery. The objective of this study was to compare the success rates of TES-MEP recordings between constant-current and constant-voltage stimulation. This is a prospective, within-subject study. Data from 100 patients undergoing spinal surgery at the cervical, thoracic, or lumbar level were analyzed. The success rates of the TES-MEP recordings from each muscle were examined. Transcranial electrical stimulation with constant-current and constant-voltage stimulations at the C3 and C4 electrode positions (international "10-20" system) was applied to each patient. Compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis (APB), deltoid (Del), abductor hallucis (AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps (Quad) muscles. The success rates of the TES-MEP recordings from the right Del, right APB, bilateral Quad, right TA, right GC, and bilateral AH muscles were significantly higher using constant-voltage stimulation than those using constant-current stimulation. The overall success rates with constant-voltage and constant-current stimulations were 86.3% and 68.8%, respectively (risk ratio 1.25 [95% confidence interval: 1.20-1.31]). The success rates of TES-MEP recordings were higher using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute effects of electromagnetic stimulation of the brain on cortical activity, cortical blood flow, blood pressure and heart rate in the cat: an evaluation of safety.

PubMed Central

Eyre, J A; Flecknell, P A; Kenyon, B R; Koh, T H; Miller, S

1990-01-01

The influence of repeated high intensity electromagnetic stimulation of the brain on cortical activity, cortical blood flow, blood pressure and heart rate has been investigated in the cat, to evaluate the safety of the method. The observations have been made in preparations under propofol anaesthesia before, during and after periods of anoxia. Electromagnetic stimulation of the brain evoked activity in descending motor pathways and was recorded by activity in the median nerve and by muscle twitches. Following repeated series of high intensity stimulation there were no systematic changes in somatosensory evoked potentials or background EEG, nor were there signs of epileptogenic activity during electromagnetic stimulation, before, during or after periods of anoxia. No systematic changes in cortical blood flow, blood pressure or heart rate were observed during electromagnetic stimulation, before or after periods of anoxia. In conclusion, no acute adverse consequences following electromagnetic stimulation in the normal and anoxic cat brain were demonstrated. PMID:2380732

Docking is not a prerequisite but a temporal constraint for fusion of secretory granules.

PubMed

Kasai, Kazuo; Fujita, Takuji; Gomi, Hiroshi; Izumi, Tetsuro

2008-07-01

We examined secretory granule dynamics using total internal reflection fluorescence microscopy in normal pancreatic beta cells and their mutants devoid of Rab27a and/or its effector, granuphilin, which play critical roles in the docking and recruitment of insulin granules to the plasma membrane. In the early phase of glucose stimulation in wild-type cells, we observed marked fusion of granules recruited from a relatively distant area, in parallel with that from granules located underneath the plasma membrane. Furthermore, despite a lack of granules directly attached to the plasma membrane, both spontaneous and evoked fusion was increased in granuphilin-null cells. In addition to these granuphilin-null phenotypes, Rab27a/granuphilin doubly deficient cells showed the decreases in granules located next to the docked area and in fusion from granules near the plasma membrane in the early phase of glucose-stimulated secretion, similar to Rab27a-mutated cells. Thus, the two proteins play nonoverlapping roles in insulin exocytosis: granuphilin acts on the granules underneath the plasma membrane, whereas Rab27a acts on those in a more distal area. These findings demonstrate that, in contrast to our conventional understanding, stable attachment of secretory granules to the plasma membrane is not prerequisite but temporally inhibitory for both spontaneous and evoked fusion.

Cortical Double-Opponent Cells in Color Perception: Perceptual Scaling and Chromatic Visual Evoked Potentials.

PubMed

Nunez, Valerie; Shapley, Robert M; Gordon, James

2018-01-01

In the early visual cortex V1, there are currently only two known neural substrates for color perception: single-opponent and double-opponent cells. Our aim was to explore the relative contributions of these neurons to color perception. We measured the perceptual scaling of color saturation for equiluminant color checkerboard patterns (designed to stimulate double-opponent neurons preferentially) and uniformly colored squares (designed to stimulate only single-opponent neurons) at several cone contrasts. The spatially integrative responses of single-opponent neurons would produce the same response magnitude for checkerboards as for uniform squares of the same space-averaged cone contrast. However, perceived saturation of color checkerboards was higher than for the corresponding squares. The perceptual results therefore imply that double-opponent cells are involved in color perception of patterns. We also measured the chromatic visual evoked potential (cVEP) produced by the same stimuli; checkerboard cVEPs were much larger than those for corresponding squares, implying that double-opponent cells also contribute to the cVEP response. The total Fourier power of the cVEP grew sublinearly with cone contrast. However, the 6-Hz Fourier component's power grew linearly with contrast-like saturation perception. This may also indicate that cortical coding of color depends on response dynamics.

[Unconscious Acoustical Stimuli Effects on Event-related Potentials in Humans].

PubMed

Kopeikina, E A; Choroshich, V V; Aleksandrov, A Y; Ivanova, V Y

2015-01-01

Unconscious perception essentially affects human behavior. The main results in this area obtained in experiments with visual stimuli. However, the acoustical stimuli play not less important role in behavior. The main idea of this paper is the electroencephalographic investigation of unconscious acoustical stimulation effects on electro-physiological activity of the brain. For this purpose, the event-related potentials were acquired under unconscious stimulus priming paradigm. The one syllable, three letter length, Russian words and pseudo-words with single letter substitution were used as primes and targets. As a result, we find out that repetition and alternative priming similarly affects the event-related potential's component with 200 ms latency after target application in frontal parietal and temporal areas. Under alternative priming the direction of potential amplitude modification nearby 400 ms was altered for word and semi-word targets. Alternative priming reliably increase ERP's amplitude in 400 ms locality with pseudo-word targets and decrease it under word targets. Taking into account, that all participants were unable to distinguish the applied prime stimuli, we can assume that the event-related potential changes evoked by unconscious perception of acoustical stimuli. The ERP amplitude dynamics revealed in current investigation demonstrate the opportunity of subliminal acoustical stimuli to modulate the electrical activity evoked by verbal acoustical stimulation.

Cortical Double-Opponent Cells in Color Perception: Perceptual Scaling and Chromatic Visual Evoked Potentials

PubMed Central

Shapley, Robert M.; Gordon, James

2018-01-01

In the early visual cortex V1, there are currently only two known neural substrates for color perception: single-opponent and double-opponent cells. Our aim was to explore the relative contributions of these neurons to color perception. We measured the perceptual scaling of color saturation for equiluminant color checkerboard patterns (designed to stimulate double-opponent neurons preferentially) and uniformly colored squares (designed to stimulate only single-opponent neurons) at several cone contrasts. The spatially integrative responses of single-opponent neurons would produce the same response magnitude for checkerboards as for uniform squares of the same space-averaged cone contrast. However, perceived saturation of color checkerboards was higher than for the corresponding squares. The perceptual results therefore imply that double-opponent cells are involved in color perception of patterns. We also measured the chromatic visual evoked potential (cVEP) produced by the same stimuli; checkerboard cVEPs were much larger than those for corresponding squares, implying that double-opponent cells also contribute to the cVEP response. The total Fourier power of the cVEP grew sublinearly with cone contrast. However, the 6-Hz Fourier component’s power grew linearly with contrast-like saturation perception. This may also indicate that cortical coding of color depends on response dynamics. PMID:29375753

Modification of activity-dependent increases in cerebellar blood flow by extracellular potassium in anaesthetized rats

PubMed Central

Caesar, Kirsten; Akgören, Nuran; Mathiesen, Claus; Lauritzen, Martin

1999-01-01

The hypothesis that potassium ions mediate activity-dependent increases of cerebral blood flow was examined in rat cerebellar cortex using ion-selective microelectrodes and laser-Doppler flowmetry. Increases of cerebellar blood flow (CeBF) and extracellular potassium concentration ([K+]o) were evoked by stimulation of parallel fibres and climbing fibres, and by microinjection of KCl into the cortex. For parallel fibre stimulation, there was a maximal increase in [K+]o to 6.3 ± 0.5 mm and in CeBF of 122 ± 11%. Climbing fibre stimulation gave a maximal increase in [K+]o to 4.4 ± 0.2 mm and in CeBF of 157 ± 20%. This indicates different maxima for [K+]o and CeBF, dependent on the afferent system activated. [K+]o and CeBF responses evoked by parallel or climbing fibre stimulation increased rapidly at the onset of stimulation, but exhibited different time courses during the remainder of the stimulation period and during return to baseline. Microinjections of KCl into the cortex increased [K+]o to levels comparable to those evoked by parallel fibre stimulation. The corresponding CeBF increases were the same as, or smaller than, for parallel fibre stimulation, and much smaller than for climbing fibre stimulation. This suggests that mediators other than [K+]o are important for activity-dependent cerebral blood flow increases. The present study showed that increased [K+]o is involved in CeBF regulation in the parallel fibre system, but is of limited importance for CeBF regulation in the climbing fibre system. The hypothesis that K+ is a major mediator of activity-dependent blood flow increases is probably not generally applicable to all brain regions and all types of neuronal stimulation. PMID:10517819

Evoked Electromyographically Controlled Electrical Stimulation

PubMed Central

Hayashibe, Mitsuhiro

2016-01-01

Time-variant muscle responses under electrical stimulation (ES) are often problematic for all the applications of neuroprosthetic muscle control. This situation limits the range of ES usage in relevant areas, mainly due to muscle fatigue and also to changes in stimulation electrode contact conditions, especially in transcutaneous ES. Surface electrodes are still the most widely used in noninvasive applications. Electrical field variations caused by changes in the stimulation contact condition markedly affect the resulting total muscle activation levels. Fatigue phenomena under functional electrical stimulation (FES) are also well known source of time-varying characteristics coming from muscle response under ES. Therefore, it is essential to monitor the actual muscle state and assess the expected muscle response by ES so as to improve the current ES system in favor of adaptive muscle-response-aware FES control. To deal with this issue, we have been studying a novel control technique using evoked electromyography (eEMG) signals to compensate for these muscle time-variances under ES for stable neuroprosthetic muscle control. In this perspective article, I overview the background of this topic and highlight important points to be aware of when using ES to induce the desired muscle activation regardless of the time-variance. I also demonstrate how to deal with the common critical problem of ES to move toward robust neuroprosthetic muscle control with the Evoked Electromyographically Controlled Electrical Stimulation paradigm. PMID:27471448

Stimulation Efficiency With Decaying Exponential Waveforms in a Wirelessly Powered Switched-Capacitor Discharge Stimulation System.

PubMed

Lee, Hyung-Min; Howell, Bryan; Grill, Warren M; Ghovanloo, Maysam

2018-05-01

The purpose of this study was to test the feasibility of using a switched-capacitor discharge stimulation (SCDS) system for electrical stimulation, and, subsequently, determine the overall energy saved compared to a conventional stimulator. We have constructed a computational model by pairing an image-based volume conductor model of the cat head with cable models of corticospinal tract (CST) axons and quantified the theoretical stimulation efficiency of rectangular and decaying exponential waveforms, produced by conventional and SCDS systems, respectively. Subsequently, the model predictions were tested in vivo by activating axons in the posterior internal capsule and recording evoked electromyography (EMG) in the contralateral upper arm muscles. Compared to rectangular waveforms, decaying exponential waveforms with time constants >500 μs were predicted to require 2%-4% less stimulus energy to activate directly models of CST axons and 0.4%-2% less stimulus energy to evoke EMG activity in vivo. Using the calculated wireless input energy of the stimulation system and the measured stimulus energies required to evoke EMG activity, we predict that an SCDS implantable pulse generator (IPG) will require 40% less input energy than a conventional IPG to activate target neural elements. A wireless SCDS IPG that is more energy efficient than a conventional IPG will reduce the size of an implant, require that less wireless energy be transmitted through the skin, and extend the lifetime of the battery in the external power transmitter.

MSG-Evoked c-Fos Activity in the Nucleus of the Solitary Tract Is Dependent upon Fluid Delivery and Stimulation Parameters.

PubMed

Stratford, Jennifer M; Thompson, John A

2016-03-01

The marker of neuronal activation, c-Fos, can be used to visualize spatial patterns of neural activity in response to taste stimulation. Because animals will not voluntarily consume aversive tastes, these stimuli are infused directly into the oral cavity via intraoral cannulae, whereas appetitive stimuli are given in drinking bottles. Differences in these 2 methods make comparison of taste-evoked brain activity between results that utilize these methods problematic. Surprisingly, the intraoral cannulae experimental conditions that produce a similar pattern of c-Fos activity in response to taste stimulation remain unexplored. Stimulation pattern (e.g., constant/intermittent) and hydration state (e.g., water-restricted/hydrated) are the 2 primary differences between delivering tastes via bottles versus intraoral cannulae. Thus, we quantified monosodium glutamate (MSG)-evoked brain activity, as measured by c-Fos, in the nucleus of the solitary tract (nTS; primary taste nucleus) across several conditions. The number and pattern of c-Fos neurons in the nTS of animals that were water-restricted and received a constant infusion of MSG via intraoral cannula most closely mimicked animals that consumed MSG from a bottle. Therefore, in order to compare c-Fos activity between cannulae-stimulated and bottle-stimulated animals, cannulated animals should be water restricted prior to stimulation, and receive taste stimuli at a constant flow. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Captured by the pain: pain steady-state evoked potentials are not modulated by selective spatial attention.

PubMed

Blöchl, Maria; Franz, Marcel; Miltner, Wolfgang H R; Weiss, Thomas

2015-04-07

Attention has been shown to affect the neural processing of pain. However, the exact mechanisms underlying this modulation remain unknown. Here, we used a new method called pain steady-state evoked potentials (PSSEPs) to investigate whether selective spatial attention affects EEG responses to tonic painful stimuli. In general, steady-state evoked potentials reflect changes in the EEG spectrum at a certain frequency that correspond to the frequency of a train of applied stimuli. In this study, high intensity transcutaneous electrical stimulation was delivered to both hands simultaneously with 31 Hz and 37 Hz, respectively. Subject׳s attention was directed to one of the two trains of stimulation in order to detect a small gap that was occasionally interspersed into the stimulus trains. Thereby, they had to ignore the stimulation applied to the other hand. Results show that PSSEPs were induced at 31 Hz and 37 Hz at frontal and central electrodes. PSSEPs occurred contralaterally to the respective hand stimulated with that frequency. Surprisingly, the magnitude of PSSEPs was not modulated by spatial attention towards one of the two stimuli. Our results indicate that attention can hardly be shifted between two simultaneously applied tonic painful stimulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Parabrachial complex glutamate receptors modulate the cardiorespiratory response evoked from hypothalamic defense area.

PubMed

Díaz-Casares, A; López-González, M V; Peinado-Aragonés, C A; González-Barón, S; Dawid-Milner, M S

2012-08-16

To characterize the possible role of glutamate in the interaction between Hypothalamic Defense Area (HDA) and Parabrachial complex (PBc) nuclei, cardiorespiratory changes were analyzed in response to electrical stimulation of the HDA (1 ms pulses, 30-50 μA given at 100 Hz for 5s) before and after the microinjection of the nonspecific glutamate receptor antagonist kynurenic acid (50 nl, 5 nmol), NMDA receptor antagonist MK-801 (50 nl, 50 nmol), non-NMDA receptor antagonist CNQX (50 nl, 50 nmol) or metabotropic glutamate receptor antagonist MCPG (50 nl, 5 nmol) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (p<0.001) due to a decrease in expiratory time (p<0.01). The respiratory response was accompanied by a pressor (p<0.001) and a tachycardic response (p<0.001). Kynurenic acid within the lateral parabrachial region (lPB) abolished the tachycardia (p<0.001) and decreased the magnitude of blood pressure response (p<0.001) to HDA stimulation. Similarly, the magnitude of the tachycardia and the pressor response was decreased after the microinjection of MK-801 (p<0.01 and p<0.001, respectively) and CNQX (p<0.05 in both cases) into the lPB. Kynurenic acid microinjection in this region produced an inhibition of the tachypnea (p<0.001) to HDA stimulation but the respiratory response persisted unchanged after MK-801 or CNQX microinjection into the lPB. Kynurenic acid within the medial parabrachial region (mPB) abolished the tachycardia (p<0.01) and decreased the magnitude of the pressor response (p<0.001) to HDA stimulation. MK-801 and CNQX microinjection in this region decreased the magnitude of the tachycardia (p<0.05, in both cases) and pressor response (p<0.05, in both cases). The respiratory response evoked by HDA stimulation was not changed after the microinjection of kynurenic acid, MK-801 or CNQX within the mPB. No changes were observed in the cardiorespiratory response evoked to HDA stimulation after MCPG microinjection within lPB and mPB. These results indicate that glutamate PBc receptors are involved in the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

EEG Brain Wave Activity at Rest and during Evoked Attention in Children with Attention-Deficit/Hyperactivity Disorder and Effects of Methylphenidate.

PubMed

Thomas, Bianca Lee; Viljoen, Margaretha

2016-01-01

The aim of this study was to assess baseline EEG brain wave activity in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of evoked attention and methylphenidate on this activity. Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulant (methylphenidate) medication. Control subjects (n = 18) were tested once. EEG brain wave activity was tested both at baseline and during focussed attention. Attention was evoked and EEG brain wave activity was determined by means of the BioGraph Infiniti biofeedback apparatus. The main finding of this study was that control subjects and stimulant-free children with ADHD exhibited the expected reactivity in high alpha-wave activity (11-12 Hz) from baseline to focussed attention; however, methylphenidate appeared to abolish this reactivity. Methylphenidate attenuates the normal cortical response to a cognitive challenge. © 2016 S. Karger AG, Basel.

Electrophysiological characterization of activation state-dependent Ca(v)2 channel antagonist TROX-1 in spinal nerve injured rats.

PubMed

Patel, R; Rutten, K; Valdor, M; Schiene, K; Wigge, S; Schunk, S; Damann, N; Christoph, T; Dickenson, A H

2015-06-25

Prialt, a synthetic version of Ca(v)2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Ca(v)2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Ca(v)2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Role of the Outer Pore Domain in Transient Receptor Potential Vanilloid 1 Dynamic Permeability to Large Cations*

PubMed Central

Munns, Clare H.; Chung, Man-Kyo; Sanchez, Yuly E.; Amzel, L. Mario; Caterina, Michael J.

2015-01-01

Transient receptor potential vanilloid 1 (TRPV1) has been shown to alter its ionic selectivity profile in a time- and agonist-dependent manner. One hallmark of this dynamic process is an increased permeability to large cations such as N-methyl-d-glucamine (NMDG). In this study, we mutated residues throughout the TRPV1 pore domain to identify loci that contribute to dynamic large cation permeability. Using resiniferatoxin (RTX) as the agonist, we identified multiple gain-of-function substitutions within the TRPV1 pore turret (N628P and S629A), pore helix (F638A), and selectivity filter (M644A) domains. In all of these mutants, maximum NMDG permeability was substantially greater than that recorded in wild type TRPV1, despite similar or even reduced sodium current density. Two additional mutants, located in the pore turret (G618W) and selectivity filter (M644I), resulted in significantly reduced maximum NMDG permeability. M644A and M644I also showed increased and decreased minimum NMDG permeability, respectively. The phenotypes of this panel of mutants were confirmed by imaging the RTX-evoked uptake of the large cationic fluorescent dye YO-PRO1. Whereas none of the mutations selectively altered capsaicin-induced changes in NMDG permeability, the loss-of-function phenotypes seen with RTX stimulation of G618W and M644I were recapitulated in the capsaicin-evoked YO-PRO1 uptake assay. Curiously, the M644A substitution resulted in a loss, rather than a gain, in capsaicin-evoked YO-PRO1 uptake. Modeling of our mutations onto the recently determined TRPV1 structure revealed several plausible mechanisms for the phenotypes observed. We conclude that side chain interactions at a few specific loci within the TRPV1 pore contribute to the dynamic process of ionic selectivity. PMID:25568328

Role of the outer pore domain in transient receptor potential vanilloid 1 dynamic permeability to large cations.

PubMed

Munns, Clare H; Chung, Man-Kyo; Sanchez, Yuly E; Amzel, L Mario; Caterina, Michael J

2015-02-27

Transient receptor potential vanilloid 1 (TRPV1) has been shown to alter its ionic selectivity profile in a time- and agonist-dependent manner. One hallmark of this dynamic process is an increased permeability to large cations such as N-methyl-D-glucamine (NMDG). In this study, we mutated residues throughout the TRPV1 pore domain to identify loci that contribute to dynamic large cation permeability. Using resiniferatoxin (RTX) as the agonist, we identified multiple gain-of-function substitutions within the TRPV1 pore turret (N628P and S629A), pore helix (F638A), and selectivity filter (M644A) domains. In all of these mutants, maximum NMDG permeability was substantially greater than that recorded in wild type TRPV1, despite similar or even reduced sodium current density. Two additional mutants, located in the pore turret (G618W) and selectivity filter (M644I), resulted in significantly reduced maximum NMDG permeability. M644A and M644I also showed increased and decreased minimum NMDG permeability, respectively. The phenotypes of this panel of mutants were confirmed by imaging the RTX-evoked uptake of the large cationic fluorescent dye YO-PRO1. Whereas none of the mutations selectively altered capsaicin-induced changes in NMDG permeability, the loss-of-function phenotypes seen with RTX stimulation of G618W and M644I were recapitulated in the capsaicin-evoked YO-PRO1 uptake assay. Curiously, the M644A substitution resulted in a loss, rather than a gain, in capsaicin-evoked YO-PRO1 uptake. Modeling of our mutations onto the recently determined TRPV1 structure revealed several plausible mechanisms for the phenotypes observed. We conclude that side chain interactions at a few specific loci within the TRPV1 pore contribute to the dynamic process of ionic selectivity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Evoked Pain Analgesia in Chronic Pelvic Pain Patients using Respiratory-gated Auricular Vagal Afferent Nerve Stimulation

PubMed Central

Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D.

2012-01-01

Objective Previous Vagus Nerve Stimulation (VNS) studies have demonstrated anti-nociceptive effects, and recent non-invasive approaches; termed transcutaneous-VNS, or t-VNS, have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Design counterbalanced, crossover study. Patients patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. Interventions/Outcomes We evaluated evoked pain analgesia for Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) compared with Non-Vagal Auricular Stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least one week apart. Outcome measures included deep tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. Results RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N=15 CPP patients, compared to NVAS, with moderate to large effect sizes (eta2>0.2). Conclusion Chronic pain disorders such as CPP are in great need of effective, non-pharmacological options for treatment. RAVANS produced promising anti-nociceptive effects for QST outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. PMID:22568773

Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats

PubMed Central

Kim, Eun Joo; Horovitz, Omer; Pellman, Blake A.; Tan, Lancy Mimi; Li, Qiuling; Richter-Levin, Gal; Kim, Jeansok J.

2013-01-01

The periaqueductal gray (PAG) and amygdala are known to be important for defensive responses, and many contemporary fear-conditioning models present the PAG as downstream of the amygdala, directing the appropriate behavior (i.e., freezing or fleeing). However, empirical studies of this circuitry are inconsistent and warrant further examination. Hence, the present study investigated the functional relationship between the PAG and amygdala in two different settings, fear conditioning and naturalistic foraging, in rats. In fear conditioning, electrical stimulation of the dorsal PAG (dPAG) produced unconditional responses (URs) composed of brief activity bursts followed by freezing and 22-kHz ultrasonic vocalization. In contrast, stimulation of ventral PAG and the basolateral amygdalar complex (BLA) evoked freezing and/or ultrasonic vocalization. Whereas dPAG stimulation served as an effective unconditional stimulus for fear conditioning to tone and context conditional stimuli, neither ventral PAG nor BLA stimulation supported fear conditioning. The conditioning effect of dPAG, however, was abolished by inactivation of the BLA. In a foraging task, dPAG and BLA stimulation evoked only fleeing toward the nest. Amygdalar lesion/inactivation blocked the UR of dPAG stimulation, but dPAG lesions did not block the UR of BLA stimulation. Furthermore, in vivo recordings demonstrated that electrical priming of the dPAG can modulate plasticity of subiculum–BLA synapses, providing additional evidence that the amygdala is downstream of the dPAG. These results suggest that the dPAG conveys unconditional stimulus information to the BLA, which directs both innate and learned fear responses, and that brain stimulation-evoked behaviors are modulated by context. PMID:23959880

ERAASR: an algorithm for removing electrical stimulation artifacts from multielectrode array recordings

NASA Astrophysics Data System (ADS)

O'Shea, Daniel J.; Shenoy, Krishna V.

2018-04-01

Objective. Electrical stimulation is a widely used and effective tool in systems neuroscience, neural prosthetics, and clinical neurostimulation. However, electrical artifacts evoked by stimulation prevent the detection of spiking activity on nearby recording electrodes, which obscures the neural population response evoked by stimulation. We sought to develop a method to clean artifact-corrupted electrode signals recorded on multielectrode arrays in order to recover the underlying neural spiking activity. Approach. We created an algorithm, which performs estimation and removal of array artifacts via sequential principal components regression (ERAASR). This approach leverages the similar structure of artifact transients, but not spiking activity, across simultaneously recorded channels on the array, across pulses within a train, and across trials. The ERAASR algorithm requires no special hardware, imposes no requirements on the shape of the artifact or the multielectrode array geometry, and comprises sequential application of straightforward linear methods with intuitive parameters. The approach should be readily applicable to most datasets where stimulation does not saturate the recording amplifier. Main results. The effectiveness of the algorithm is demonstrated in macaque dorsal premotor cortex using acute linear multielectrode array recordings and single electrode stimulation. Large electrical artifacts appeared on all channels during stimulation. After application of ERAASR, the cleaned signals were quiescent on channels with no spontaneous spiking activity, whereas spontaneously active channels exhibited evoked spikes which closely resembled spontaneously occurring spiking waveforms. Significance. We hope that enabling simultaneous electrical stimulation and multielectrode array recording will help elucidate the causal links between neural activity and cognition and facilitate naturalistic sensory protheses.

Electrical stimulation of the midbrain excites the auditory cortex asymmetrically.

PubMed

Quass, Gunnar Lennart; Kurt, Simone; Hildebrandt, Jannis; Kral, Andrej

2018-05-17

Auditory midbrain implant users cannot achieve open speech perception and have limited frequency resolution. It remains unclear whether the spread of excitation contributes to this issue and how much it can be compensated by current-focusing, which is an effective approach in cochlear implants. The present study examined the spread of excitation in the cortex elicited by electric midbrain stimulation. We further tested whether current-focusing via bipolar and tripolar stimulation is effective with electric midbrain stimulation and whether these modes hold any advantage over monopolar stimulation also in conditions when the stimulation electrodes are in direct contact with the target tissue. Using penetrating multielectrode arrays, we recorded cortical population responses to single pulse electric midbrain stimulation in 10 ketamine/xylazine anesthetized mice. We compared monopolar, bipolar, and tripolar stimulation configurations with regard to the spread of excitation and the characteristic frequency difference between the stimulation/recording electrodes. The cortical responses were distributed asymmetrically around the characteristic frequency of the stimulated midbrain region with a strong activation in regions tuned up to one octave higher. We found no significant differences between monopolar, bipolar, and tripolar stimulation in threshold, evoked firing rate, or dynamic range. The cortical responses to electric midbrain stimulation are biased towards higher tonotopic frequencies. Current-focusing is not effective in direct contact electrical stimulation. Electrode maps should account for the asymmetrical spread of excitation when fitting auditory midbrain implants by shifting the frequency-bands downward and stimulating as dorsally as possible. Copyright © 2018 Elsevier Inc. All rights reserved.

Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque

NASA Astrophysics Data System (ADS)

Davis, T. S.; Parker, R. A.; House, P. A.; Bagley, E.; Wendelken, S.; Normann, R. A.; Greger, B.

2012-12-01

Objective. It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. Approach. An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. Main results. The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

Vestibular Evoked Myogenic Potential Produced by Bone-Conducted Stimuli: A Study on its Basics and Clinical Applications in Patients with Conductive and Sensorineural Hearing Loss and a Group with Vestibular Schawannoma.

PubMed

Mahdi, Parvane; Amali, Amin; Pourbakht, Akram; Karimi Yazdi, Alireza; Bassam, Ali

2013-06-01

Vestibular evoked myogenic potential (VEMP) has recently been broadly studied in vestibular disorders. As it is evoked by loud sound stimulation, even mild conductive hearing loss may affect VEMP results. Bone-conducted (BC) stimulus is an alternative stimulation for evoking this response. This study aims to assess the characteristics of BC-VEMP in different groups of patients. We performed a cross sectional analysis on 20 healthy volunteers with normal pure-tone audiometry as a control group; and on a group of patients consisted of 20 participants with conductive hearing loss, five with bilateral sensorineural hearing loss and four with vestibular schawannoma. AC and BC-VEMP were performed in all participants. In control group the VEMP responses to both kinds of stimuli had an acceptable morphology and consisted of p13 and n23 waves. Latency value of these main components in each type of stimulus was not significantly different (P>0.05). However, the mean amplitude was larger in BC modality than AC stimulation (P=0.025). In the group with conductive hearing loss, the VEMP response was absent in fifteen (46.87%) of the 32 ears using the AC method, whereas all (100%) displayed positive elicitability of VEMP by BC method. Normal VEMP responses in both stimuli were evoked in all patients with sensorineural hearing loss. In patients with unilateral vestibular schwannomas (VS), 2 (50.00%) had neither AC-VEMP nor BC-VEMP. Auditory stimuli delivered by bone conduction can evoke VEMP response. These responses are of vestibular origin and can be used in vestibular evaluation of patients with conductive hearing loss.

Vestibular Evoked Myogenic Potential Produced by Bone-Conducted Stimuli: A Study on its Basics and Clinical Applications in Patients with Conductive and Sensorineural Hearing Loss and a Group with Vestibular Schawannoma

PubMed Central

Mahdi, Parvane; Amali, Amin; Pourbakht, Akram; Karimi Yazdi, Alireza; Bassam, Ali

2013-01-01

Introduction: Vestibular evoked myogenic potential (VEMP) has recently been broadly studied in vestibular disorders. As it is evoked by loud sound stimulation, even mild conductive hearing loss may affect VEMP results. Bone-conducted (BC) stimulus is an alternative stimulation for evoking this response. This study aims to assess the characteristics of BC-VEMP in different groups of patients. Materials and Methods: We performed a cross sectional analysis on 20 healthy volunteers with normal pure-tone audiometry as a control group; and on a group of patients consisted of 20 participants with conductive hearing loss, five with bilateral sensorineural hearing loss and four with vestibular schawannoma. AC and BC-VEMP were performed in all participants. Results: In control group the VEMP responses to both kinds of stimuli had an acceptable morphology and consisted of p13 and n23 waves. Latency value of these main components in each type of stimulus was not significantly different (P>0.05). However, the mean amplitude was larger in BC modality than AC stimulation (P=0.025). In the group with conductive hearing loss, the VEMP response was absent in fifteen (46.87%) of the 32 ears using the AC method, whereas all (100%) displayed positive elicitability of VEMP by BC method. Normal VEMP responses in both stimuli were evoked in all patients with sensorineural hearing loss. In patients with unilateral vestibular schwannomas (VS), 2 (50.00%) had neither AC-VEMP nor BC-VEMP. Conclusion: Auditory stimuli delivered by bone conduction can evoke VEMP response. These responses are of vestibular origin and can be used in vestibular evaluation of patients with conductive hearing loss. PMID:24303434

Kinematics and eye-head coordination of gaze shifts evoked from different sites in the superior colliculus of the cat.

PubMed

Guillaume, Alain; Pélisson, Denis

2006-12-15

Shifting gaze requires precise coordination of eye and head movements. It is clear that the superior colliculus (SC) is involved with saccadic gaze shifts. Here we investigate its role in controlling both eye and head movements during gaze shifts. Gaze shifts of the same amplitude can be evoked from different SC sites by controlled electrical microstimulation. To describe how the SC coordinates the eye and the head, we compare the characteristics of these amplitude-matched gaze shifts evoked from different SC sites. We show that matched amplitude gaze shifts elicited from progressively more caudal sites are progressively slower and associated with a greater head contribution. Stimulation at more caudal SC sites decreased the peak velocity of the eye but not of the head, suggesting that the lower peak gaze velocity for the caudal sites is due to the increased contribution of the slower-moving head. Eye-head coordination across the SC motor map is also indicated by the relative latencies of the eye and head movements. For some amplitudes of gaze shift, rostral stimulation evoked eye movement before head movement, whereas this reversed with caudal stimulation, which caused the head to move before the eyes. These results show that gaze shifts of similar amplitude evoked from different SC sites are produced with different kinematics and coordination of eye and head movements. In other words, gaze shifts evoked from different SC sites follow different amplitude-velocity curves, with different eye-head contributions. These findings shed light on mechanisms used by the central nervous system to translate a high-level motor representation (a desired gaze displacement on the SC map) into motor commands appropriate for the involved body segments (the eye and the head).

Temperature perception on the hand during static vs. dynamic contact with a surface

PubMed Central

Green, Barry G.

2010-01-01

Innocuous cooling or heating of the forearm can evoke nociceptive sensations such as burning, stinging, and pricking (‘low-threshold thermal nociception’, LTN) that are inhibited by dynamic contact. The present study investigated whether LTN can also be perceived on the hand, and if so, whether it is normally suppressed by active touching. Innocuous cold (28°, 25° and 18°C) and warm (38°, 40° and 43°C) temperatures were delivered to the distal metacarpal pads and intermediate and distal phalanges of the fingers via a handgrip thermode that subjects either statically held or actively grasped. The same temperatures were delivered to the forearm via another thermode that either rested on the arm or was touched to the arm. Subjects rated the intensity of thermal (warmth, cold) and nociceptive (e.g., burning) sensations and indicated the qualities of sensation experienced. The results showed that LTN can be perceived on the hand, although less frequently and less intensely than on the forearm. Dynamic contact inhibited nociceptive and thermal sensations on the hand, though less strongly than on the forearm. These findings indicate that temperature perception on the hand is attenuated and its quality changed when thermal stimulation is accompanied by dynamic tactile stimulation, as during haptic exploration. PMID:19525547

A voltage-controlled capacitive discharge method for electrical activation of peripheral nerves.

PubMed

Rosellini, Will M; Yoo, Paul B; Engineer, Navzer; Armstrong, Scott; Weiner, Richard L; Burress, Chester; Cauller, Larry

2011-01-01

A voltage-controlled capacitive discharge (VCCD) method was investigated as an alternative to rectangular stimulus pulses currently used in peripheral nerve stimulation therapies.  In two anesthetized Gottingen mini pigs, the threshold (total charge per phase) for evoking a compound nerve action potential (CNAP) was compared between constant current (CC) and VCCD methods. Electrical pulses were applied to the tibial and posterior cutaneous femoralis nerves using standard and modified versions of the Medtronic 3778 Octad.  In contrast to CC stimulation, the combined application of VCCD pulses with a modified Octad resulted in a marked decrease (-73 ± 7.4%) in the stimulation threshold for evoking a CNAP. This was consistent for different myelinated fiber types and locations of stimulation.  The VCCD method provides a highly charge-efficient means of activating myelinated fibers that could potentially be used within a wireless peripheral nerve stimulator system. © 2011 International Neuromodulation Society.

Distributed stimulation increases force elicited with functional electrical stimulation

NASA Astrophysics Data System (ADS)

Buckmire, Alie J.; Lockwood, Danielle R.; Doane, Cynthia J.; Fuglevand, Andrew J.

2018-04-01

Objective. The maximum muscle forces that can be evoked using functional electrical stimulation (FES) are relatively modest. The reason for this weakness is not fully understood but could be partly related to the widespread distribution of motor nerve branches within muscle. As such, a single stimulating electrode (as is conventionally used) may be incapable of activating the entire array of motor axons supplying a muscle. Therefore, the objective of this study was to determine whether stimulating a muscle with more than one source of current could boost force above that achievable with a single source. Approach. We compared the maximum isometric forces that could be evoked in the anterior deltoid of anesthetized monkeys using one or two intramuscular electrodes. We also evaluated whether temporally interleaved stimulation between two electrodes might reduce fatigue during prolonged activity compared to synchronized stimulation through two electrodes. Main results. We found that dual electrode stimulation consistently produced greater force (~50% greater on average) than maximal stimulation with single electrodes. No differences, however, were found in the fatigue responses using interleaved versus synchronized stimulation. Significance. It seems reasonable to consider using multi-electrode stimulation to augment the force-generating capacity of muscles and thereby increase the utility of FES systems.

Release of substance P from the cat spinal cord.

PubMed Central

Go, V L; Yaksh, T L

1987-01-01

1. The present experiments examine the physiology and pharmacology of the release of substance P-like immunoreactivity (SP-l.i.), from the spinal cord in the halothane-anaesthetized, artificially ventilated cat. 2. Resting release of SP-l.i. was 36 +/- 4 fmol/30 min (mean +/- S.E.; n = 106). Bilateral stimulation of the sciatic nerves at intensities which evoked activity in fibres conducting at A beta conduction velocities (greater than 40 m/s), resulted in no change in blood pressure, pupil diameter or release of SP-l.i. Stimulation intensities which activate fibres conducting at velocities less than 2 m/s resulted in increased blood pressure, miosis and elevated release of SP-l.i. (278 +/- 16% of control). 3. The relationship between nerve-stimulation frequency and release was monotonic up to approximately 20 Hz. Higher stimulation frequencies did not increase the amounts of SP-l.i. released. At 200 Hz there was a reduction. 4. Capsaicin (0.1 mM) increased the release of SP-l.i. from the spinal cord and resulted in an acute desensitization to subsequent nerve stimulation. This acute effect was not accompanied by a reduction in spinal levels of SP-l.i. measured 2 h after stimulation. 5. Cold block of the cervical spinal cord resulted in an increase in the amounts of SP-l.i. released by nerve stimulation. 6. Pre-treatment with intrathecal 5,6-dihydroxytryptamine (300 micrograms) 7 days prior to the experiment caused a reduction in the dorsal and ventral horn stores of SP-l.i., but had no effect on the release of SP-l.i. evoked by nerve stimulation. Similar pre-treatment with intrathecal capsaicin (300 micrograms) resulted in depletion of SP-l.i. in the dorsal but not in the ventral horn of the spinal cord and diminished the release of SP-l.i. evoked by nerve stimulation. 7. Intense thermal stimulation of the flank resulted in small (20-35%), but reliable increases in the release of SP-l.i. above control. 8. Putative agonists for the opioid mu-receptor (morphine, 10-100 microM; sufentanil, 1 microM), and for the delta-receptor (D-Ala2-D-Leu5-enkephalin, 1-10 microM; D-Pen2-D-Pen5-enkephalin, 10 microM), but not the kappa-receptor (U50488H, 100-1000 microM), produced a dose-dependent, naloxone-reversible reduction of the evoked, but not of the resting release of SP-l.i. (-)-Naloxone, but not (+)-naloxone, resulted in a significant increase in evoked but not resting SP-l.i. release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2451003

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation.

PubMed

Neuling, Toralf; Ruhnau, Philipp; Fuscà, Marco; Demarchi, Gianpaolo; Herrmann, Christoph S; Weisz, Nathan

2015-09-01

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior. Copyright © 2015. Published by Elsevier Inc.

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation

PubMed Central

Neuling, Toralf; Ruhnau, Philipp; Fuscà, Marco; Demarchi, Gianpaolo; Herrmann, Christoph S.; Weisz, Nathan

2015-01-01

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior. PMID:26080310

A Micro-Electrode Array device coupled to a laser-based system for the local stimulation of neurons by optical release of glutamate.

PubMed

Ghezzi, Diego; Menegon, Andrea; Pedrocchi, Alessandra; Valtorta, Flavia; Ferrigno, Giancarlo

2008-10-30

Optical stimulation is a promising approach to investigate the local dynamic responses of cultured neurons. In particular, flash photolysis of caged compounds offers the advantage of allowing the rapid change of concentration of either extracellular or intracellular molecules, such as neurotransmitters or second messengers, for the stimulation or modulation of neuronal activity. We describe here the use of an ultra-violet (UV) laser diode coupled to an optical fibre for the local activation of caged compounds combined with a Micro-Electrode Array (MEA) device. Local uncaging was achieved by UV irradiation through the optical fibre previously positioned by using a red laser diode. The size of the stimulation was determined using caged fluorescein, whereas its efficacy was tested by studying the effect of uncaging the neurotransmitter glutamate. Uncaged glutamate evoked neuronal responses that were recorded using either fluorescence measurements or electrophysiological recordings with MEAs, thus showing the ability of our system to induce local neuronal excitation. This method allows overcoming the limitations of the MEA system related to unfocused electrical stimulation and induction of electrical artefacts. In addition, the coupling of a UV laser diode to an optical fibre allows a precise local stimulation and a quick change of the stimulation point.

Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus tractus solitarii.

PubMed Central

Silva-Carvalho, L; Dawid-Milner, M S; Goldsmith, G E; Spyer, K M

1995-01-01

1. There is evidence in the literature of a mutual facilitatory interaction between the arterial chemoreceptor reflex and the alerting stage of the defence reaction, particularly in relation to the patterning of cardiorespiratory activity. The present study has been designed to test the hypothesis that a portion of this interaction involves synaptic interactions within the nucleus tractus solitarii (NTS). 2. The study has involved an analysis of the effective interactions between the stimulation of the arterial chemoreceptors and the hypothalamic defence area (HDA) on the activity of NTS neurones recorded in anaesthetized, paralysed and artificially ventilated cats. 3. A group of eighteen NTS neurones was classified as chemosensitive, on the basis of displaying EPSPs on sinus nerve stimulation (SN) and their failure to show an excitatory response to baroreceptor stimulation. Thirteen of these neurones displayed pronounced excitatory responses to chemoreceptor stimulation. In sixteen of these neurones HDA stimulation elicited an EPSP; in four of these sixteen neurones this early EPSP was followed by an IPSP. In the remaining two (of 18) neurones HDA stimulation provoked no obvious synaptic response but facilitated the efficacy of both chemoreceptor inputs and SN stimulation. 4. Neurones shown to receive convergent inputs from the arterial chemoreceptors (and SN stimulation) and HDA, often displayed excitatory responses to stimulation of other peripheral inputs. Vagally evoked EPSPs were observed in nine neurones, SLN-evoked responses in seven neurones and aortic nerve-evoked EPSPs in three neurones. 5. The organization of these synaptic interactions is discussed and these data are used to explain the pattern of interaction between chemoreceptor, baroreceptor and HDA inputs within the NTS. Conclusions are drawn regarding the functional role of different classes of NTS neurone, based on the findings in this and the accompanying two papers. PMID:8544136

Multifunctional System for Observing, Measuring and Analyzing Stimulation-Evoked Neurochemical Signaling

PubMed Central

Kimble, Christopher J.; Boesche, Joshua B.; Eaker, Diane R.; Kressin, Kenneth R.; Trevathan, James K.; Paek, Seungleal; Asp, Anders J.; McIntosh, Malcolm B.; Lujan, J. Luis

2017-01-01

The ability to measure neurotransmitter activity using implanted electrochemical sensors offers researchers a potent technique for analyzing neural activity across specific neural circuitry. We have developed a wirelessly controlled device, WINCS Harmoni, to observe and measure neurotransmitter dynamics at up to four separate sensors, with high temporal and spatial resolution. WINCS Harmoni also incorporates a versatile neurostimulator that can be synchronized with electrochemical recording. The WINCS Harmoni platform is thus optimally suited for probing the neurochemical effects of neurostimulation, and may in turn enable the development of personalized therapies for multiple brain disorders. PMID:29202131

Changes in mechanical, chemical, and thermal sensitivity of the cornea after topical application of nonsteroidal anti-inflammatory drugs.

PubMed

Acosta, M Carmen; Berenguer-Ruiz, Leticia; García-Gálvez, Alberto; Perea-Tortosa, David; Gallar, Juana; Belmonte, Carlos

2005-01-01

In addition to their well-known anti-inflammatory actions, some of the nonsteroidal anti-inflammatory drugs (NSAIDs) appear to have an analgesic effect. In human subjects, the changes in threshold and intensity of sensations evoked by mechanical, chemical, and thermal stimulation of the cornea induced by topical administration of two commercial NSAIDs, diclofenac sodium (Voltaren; Novartis, Basel, Switzerland) and flurbiprofen (Ocuflur; Allergan, Irvine, CA), were studied. Corneal sensitivity was measured in 10 young, healthy subjects with a gas esthesiometer. Chemical (10%-70% CO2 in air), mechanical (0-264 mL/min), and thermal (corneal temperature changes between -4.5 degrees C and +3 degrees C around the normal value) stimuli were applied to the center of the cornea. The intensity and perceived magnitude of the psychophysical attributes of the evoked sensation were scored at the end of the pulse in a 10-cm, continuous visual analog scale (VAS). The threshold was expressed as the stimulus intensity that evoked a VAS score >0.5. Sensitivity was measured in both eyes of each subject on two separate days, one without treatment and the other 30 minutes after topical application of 0.03% flurbiprofen (seven subjects) or 0.1% diclofenac sodium (six subjects). Diclofenac attenuated significantly all the sensation parameters evoked by high-intensity mechanical, chemical, and thermal stimuli. Flurbiprofen produced a slight reduction of the sensations evoked by mechanical and chemical stimulation that became significant only for the irritation caused by chemical stimuli of maximum intensity (70% CO2). None of the drugs modified significantly the detection threshold of the different stimuli. Flurbiprofen had a very limited effect on sensations evoked by corneal stimulation, whereas diclofenac reduced the intensity of sensations evoked by stimuli of different modality, suggesting a mild local anesthetic effect of this drug on all types of corneal sensory fibers. Such anesthetic action could explain the analgesic effect that has been reported after topical application of diclofenac in inflamed human eyes.

Interaction between protein kinase C and protein kinase A can modulate transmitter release at the rat neuromuscular synapse.

PubMed

Santafé, M M; Garcia, N; Lanuza, M A; Tomàs, M; Tomàs, J

2009-02-15

We used intracellular recording to investigate the functional interaction between protein kinase C (PKC) and protein kinase A (PKA) signal transduction cascades in the control of transmitter release in the neuromuscular synapses from adult rats. Our results indicate that: 1) PKA and PKC are independently involved in asynchronous release. 2) Evoked acetylcholine (ACh) release is enhanced with the PKA agonist Sp-8-BrcAMP and the PKC agonist phorbol ester (PMA). 3) PKA has a constitutive role in promoting a component of normal evoked transmitter release because, when the kinase is inhibited with H-89, the release diminishes. However, the PKC inhibitor calphostin C (CaC) does not affect ACh release. 4) PKA regulates neurotransmission without PKC involvement because, after PMA or CaC modulation of the PKC activity, coupling to the ACh release of PKA can normally be stimulated with Sp-8-BrcAMP or inhibited with H-89. 5) After PKA inhibition with H-89, PKC stimulation with PMA (or inhibition with CaC) does not lead to any change in evoked ACh release. However, in PKA-stimulated preparations with Sp-8-BrcAMP, PKC becomes tonically active, thus potentiating a component of release that can now be blocked with CaC. In normal conditions, therefore, PKA was able to modulate ACh release independently of PKC activity, whereas PKA stimulation caused the PKC coupling to evoked release. In contrast, PKA inhibition prevent PKC stimulation (with the phorbol ester) and coupling to ACh output. There was therefore some dependence of PKC on PKA activity in the fine control of the neuromuscular synaptic functionalism and ACh release.

Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei

PubMed Central

Brunert, Daniela; Tsuno, Yusuke; Rothermel, Markus; Shipley, Michael T.

2016-01-01

Serotonergic neurons in the brainstem raphe nuclei densely innervate the olfactory bulb (OB), where they can modulate the initial representation and processing of olfactory information. Serotonergic modulation of sensory responses among defined OB cell types is poorly characterized in vivo. Here, we used cell-type-specific expression of optical reporters to visualize how raphe stimulation alters sensory responses in two classes of GABAergic neurons of the mouse OB glomerular layer, periglomerular (PG) and short axon (SA) cells, as well as mitral/tufted (MT) cells carrying OB output to piriform cortex. In PG and SA cells, brief (1–4 s) raphe stimulation elicited a large increase in the magnitude of responses linked to inhalation of ambient air, as well as modest increases in the magnitude of odorant-evoked responses. Near-identical effects were observed when the optical reporter of glutamatergic transmission iGluSnFR was expressed in PG and SA cells, suggesting enhanced excitatory input to these neurons. In contrast, in MT cells imaged from the dorsal OB, raphe stimulation elicited a strong increase in resting GCaMP fluorescence with only a slight enhancement of inhalation-linked responses to odorant. Finally, optogenetically stimulating raphe serotonergic afferents in the OB had heterogeneous effects on presumptive MT cells recorded extracellularly, with an overall modest increase in resting and odorant-evoked responses during serotonergic afferent stimulation. These results suggest that serotonergic afferents from raphe dynamically modulate olfactory processing through distinct effects on multiple OB targets, and may alter the degree to which OB output is shaped by inhibition during behavior. SIGNIFICANCE STATEMENT Modulation of the circuits that process sensory information can profoundly impact how information about the external world is represented and perceived. This study investigates how the serotonergic system modulates the initial processing of olfactory information by the olfactory bulb, an obligatory relay between sensory neurons and cortex. We find that serotonergic projections from the raphe nuclei to the olfactory bulb dramatically enhance the responses of two classes of inhibitory interneurons to sensory input, that this effect is mediated by increased glutamatergic drive onto these neurons, and that serotonergic afferent activation alters the responses of olfactory bulb output neurons in vivo. These results elucidate pathways by which neuromodulatory systems can dynamically regulate brain circuits during behavior. PMID:27335411

Vomiting Center reanalyzed: An electrical stimulation study

NASA Technical Reports Server (NTRS)

Miller, A. D.; Wilson, V. J.

1982-01-01

Electrical stimulation of the brainstem of 15 decerebrate cats produced stimulus-bound vomiting in only 4 animals. Vomiting was reproducible in only one cat. Effective stimulating sites were located in the solitary tract and reticular formation. Restricted localization of a vomiting center, stimulation of which evoked readily reproducible results, could not be obtained.

Direct sensorimotor corticospinal modulation of dorsal horn neuronal C-fiber responses in the rat.

PubMed

Rojas-Piloni, Gerardo; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rodríguez-Jiménez, Javier

2010-09-10

Clinically, the stimulation of motor cortical areas has been used to alleviate certain pain conditions. However, the attempts to understand the mechanisms of cortical nociceptive modulation at the spinal cord level have yielded controversial results. The objectives of the present work were to: 1) determine the effects of activating and suppressing the activity of sensorimotor cortical neurons on the nociceptive electrophysiological responses of the segmental C-fibers, and 2) evaluate the contribution of direct and indirect corticospinal projections in segmental nociceptive modulation. By means of a bipolar matrix of stimulation electrodes we mapped the stimulation of cortical areas that modulate C-fiber evoked field potentials in the dorsal horn. In addition, suppressing the cortical activity by means of cortical spreading depression, we observed that the C-fiber evoked field potentials in the dorsal horn are facilitated when cortical activity is suppressed specifically in sensorimotor cortex. Moreover, the C-fiber evoked field potentials were inhibited during spontaneous activation of cortical projecting neurons. Furthermore, after a lesion of the pyramidal tract contralateral to the spinal cord recording sites, the cortical action was suppressed. Our results show that corticospinal tract fibers arising from the sensorimotor cortex modulate directly the nociceptive C-fiber evoked responses of the dorsal horn. 2010. Published by Elsevier B.V.

Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex

PubMed Central

Sreenivasan, Varun; Kyriakatos, Alexandros; Mateo, Celine; Jaeger, Dieter; Petersen, Carl C.H.

2016-01-01

Abstract. The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs. PMID:27921067

Temporal Code-Driven Stimulation: Definition and Application to Electric Fish Signaling

PubMed Central

Lareo, Angel; Forlim, Caroline G.; Pinto, Reynaldo D.; Varona, Pablo; Rodriguez, Francisco de Borja

2016-01-01

Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox. PMID:27766078

Temporal Code-Driven Stimulation: Definition and Application to Electric Fish Signaling.

PubMed

Lareo, Angel; Forlim, Caroline G; Pinto, Reynaldo D; Varona, Pablo; Rodriguez, Francisco de Borja

2016-01-01

Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox.

Pulsed laser versus electrical energy for peripheral nerve stimulation

PubMed Central

Wells, Jonathon; Konrad, Peter; Kao, Chris; Jansen, E. Duco; Mahadevan-Jansen, Anita

2010-01-01

Transient optical neural stimulation has previously been shown to elicit highly controlled, artifact-free potentials within the nervous system in a non-contact fashion without resulting in damage to tissue. This paper presents the physiologic validity of elicited nerve and muscle potentials from pulsed laser induced stimulation of the peripheral nerve in a comparative study with the standard method of electrically evoked potentials. Herein, the fundamental physical properties underlying the two techniques are contrasted. Key laser parameters for efficient optical stimulation of the peripheral nerve are detailed. Strength response curves are shown to be linear for each stimulation modality, although fewer axons can be recruited with optically evoked potentials. Results compare the relative transient energy requirements for stimulation using each technique and demonstrate that optical methods can selectively excite functional nerve stimulation. Adjacent stimulation and recording of compound nerve potentials in their entirety from optical and electrical stimulation are presented, with optical responses shown to be free of any stimulation artifact. Thus, use of a pulsed laser exhibits some advantages when compared to standard electrical means for excitation of muscle potentials in the peripheral nerve in the research domain and possibly for clinical diagnostics in the future. PMID:17537515

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network.

PubMed

Segers, L S; Nuding, S C; Ott, M M; Dean, J B; Bolser, D C; O'Connor, R; Morris, K F; Lindsey, B G

2015-01-01

Models of brain stem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that "tonic" pericolumnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multielectrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by cross-correlogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pairwise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In five animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons. Copyright © 2015 the American Physiological Society.

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network

PubMed Central

Segers, L. S.; Nuding, S. C.; Ott, M. M.; Dean, J. B.; Bolser, D. C.; O'Connor, R.; Morris, K. F.

2014-01-01

Models of brain stem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that “tonic” pericolumnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multielectrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by cross-correlogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pairwise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In five animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons. PMID:25343784

Chronic Electrical Stimulation with a Suprachoroidal Retinal Prosthesis: A Preclinical Safety and Efficacy Study

PubMed Central

Nayagam, David A. X.; Williams, Richard A.; Allen, Penelope J.; Shivdasani, Mohit N.; Luu, Chi D.; Salinas-LaRosa, Cesar M.; Finch, Sue; Ayton, Lauren N.; Saunders, Alexia L.; McPhedran, Michelle; McGowan, Ceara; Villalobos, Joel; Fallon, James B.; Wise, Andrew K.; Yeoh, Jonathan; Xu, Jin; Feng, Helen; Millard, Rodney; McWade, Melanie; Thien, Patrick C.; Williams, Chris E.; Shepherd, Robert K.

2014-01-01

Purpose To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis. Methods Seven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue. Results All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses. Conclusions Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents. PMID:24853376

Torque decrease during submaximal evoked contractions of the quadriceps muscle is linked not only to muscle fatigue.

PubMed

Matkowski, Boris; Lepers, Romuald; Martin, Alain

2015-05-01

The aim of this study was to analyze the neuromuscular mechanisms involved in the torque decrease induced by submaximal electromyostimulation (EMS) of the quadriceps muscle. It was hypothesized that torque decrease after EMS would reflect the fatigability of the activated motor units (MUs), but also a reduction in the number of MUs recruited as a result of changes in axonal excitability threshold. Two experiments were performed on 20 men to analyze 1) the supramaximal twitch superimposed and evoked at rest during EMS (Experiment 1, n = 9) and 2) the twitch response and torque-frequency relation of the MUs activated by EMS (Experiment 2, n = 11). Torque loss was assessed by 15 EMS-evoked contractions (50 Hz; 6 s on/6 s off), elicited at a constant intensity that evoked 20% of the maximal voluntary contraction (MVC) torque. The same stimulation intensity delivered over the muscles was used to induce the torque-frequency relation and the single electrical pulse evoked after each EMS contraction (Experiment 2). In Experiment 1, supramaximal twitch was induced by femoral nerve stimulation. Torque decreased by ~60% during EMS-evoked contractions and by only ~18% during MVCs. This was accompanied by a rightward shift of the torque-frequency relation of MUs activated and an increase of the ratio between the superimposed and posttetanic maximal twitch evoked during EMS contraction. These findings suggest that the torque decrease observed during submaximal EMS-evoked contractions involved muscular mechanisms but also a reduction in the number of MUs recruited due to changes in axonal excitability. Copyright © 2015 the American Physiological Society.

The development and modeling of devices and paradigms for transcranial magnetic stimulation

PubMed Central

Goetz, Stefan M.; Deng, Zhi-De

2017-01-01

Magnetic stimulation is a noninvasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modeling. PMID:28443696

The development and modelling of devices and paradigms for transcranial magnetic stimulation.

PubMed

Goetz, Stefan M; Deng, Zhi-De

2017-04-01

Magnetic stimulation is a non-invasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain, as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modelling.

WITHIN-SESSION CHANGES IN PEAK N160 AMPLITUDE OF FLASH EVOKED POTENTIALS IN RATS

EPA Science Inventory

The negative peak occurring approximately 160 msec after stimulation (peak N 160) flash evoked potentials (FEPS) of rats changes with repeated testing. abituation, sensitization, and arousal have all been invoked to explain these changes, but few studies have directly tested thes...

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss.

PubMed

Li, L P H; Shiao, A S; Chen, L F; Niddam, D M; Chang, S Y; Lien, C F; Lee, S K; Hsieh, J C

2006-08-01

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.

Combination of High-density Microelectrode Array and Patch Clamp Recordings to Enable Studies of Multisynaptic Integration.

PubMed

Jäckel, David; Bakkum, Douglas J; Russell, Thomas L; Müller, Jan; Radivojevic, Milos; Frey, Urs; Franke, Felix; Hierlemann, Andreas

2017-04-20

We present a novel, all-electric approach to record and to precisely control the activity of tens of individual presynaptic neurons. The method allows for parallel mapping of the efficacy of multiple synapses and of the resulting dynamics of postsynaptic neurons in a cortical culture. For the measurements, we combine an extracellular high-density microelectrode array, featuring 11'000 electrodes for extracellular recording and stimulation, with intracellular patch-clamp recording. We are able to identify the contributions of individual presynaptic neurons - including inhibitory and excitatory synaptic inputs - to postsynaptic potentials, which enables us to study dendritic integration. Since the electrical stimuli can be controlled at microsecond resolution, our method enables to evoke action potentials at tens of presynaptic cells in precisely orchestrated sequences of high reliability and minimum jitter. We demonstrate the potential of this method by evoking short- and long-term synaptic plasticity through manipulation of multiple synaptic inputs to a specific neuron.

Thoracic vagal efferent nerve stimulation evokes substance P-induced early airway bronchonstriction and late proinflammatory and oxidative injury in the rat respiratory tract.

PubMed

Li, Ping-Chia; Li, Sheng-Chung; Lin, Yuan-Ju; Liang, Jin-Tung; Chien, Chiang-Ting; Shaw, Chen-Fu

2005-01-01

Electrical stimulation of efferent thoracic vagus nerve (TVN) evoked neurogenic inflammation in respiratory tract of atropine-treated rats by an undefined mechanism. We explored whether efferent TVN stimulation via substance P facilitates neurogenic inflammation via action of nuclear factor-kappaB (NF-kappaB) activation and reactive oxygen species (ROS) production. Our results showed that increased frequency of TVN stimulation concomitantly increased substance P-enhanced hypotension, and bronchoconstriction (increases in smooth muscle electromyographic activity and total pulmonary resistance). The enhanced SP release evoked the appearance of endothelial gap in silver-stained leaky venules, India-ink labeled extravasation, and accumulations of inflammatory cells in the respiratory tract, contributing to trachea plasma extravasation as well as increases in blood O (2)(-) and H(2)O(2) ROS amount. L-732138 (NK(1) receptor antagonist), SR-48968 (NK(2) receptor antagonist), dimethylthiourea (H(2)O(2) scavenger) or catechins (O (2)(-) and H(2)O(2) scavenger) pretreatment reduced efferent TVN stimulation-enhanced hypotension, bronchoconstriction, and plasma extravasation. Increased frequency of TVN stimulation significantly upregulated the expression of nuclear factor-kappaB (NF-kappaB) in nuclear protein and intercellular adhesion molecule-1 (ICAM-1) in total protein of the lower respiratory tract tissue. The upregulation of NF-kappaB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants. In conclusion, TVN efferent stimulation increases substance P release to trigger NF-kappaB mediated ICAM-1 expression and O (2)(-) and H(2)O(2) ROS production in the respiratory tract.

Keep Away from Danger: Dangerous Objects in Dynamic and Static Situations

PubMed Central

Anelli, Filomena; Nicoletti, Roberto; Bolzani, Roberto; Borghi, Anna M.

2013-01-01

Behavioral and neuroscience studies have shown that objects observation evokes specific affordances (i.e., action possibilities) and motor responses. Recent findings provide evidence that even dangerous objects can modulate the motor system evoking aversive affordances. This sounds intriguing since so far the majority of behavioral, brain imaging, and transcranial magnetic stimulation studies with painful and dangerous stimuli strictly concerned the domain of pain, with the exception of evidence suggesting sensitivity to objects’ affordances when neutral objects are located in participants’ peripersonal space. This study investigates whether the observation of a neutral or dangerous object in a static or dynamic situation differently influences motor responses, and the time-course of the dangerous objects’ processing. In three experiments we manipulated: object dangerousness (neutral vs. dangerous); object category (artifact vs. natural); manual response typology (press vs. release a key); object presentation (Experiment 1: dynamic, Experiments 2 and 3: static); object movement direction (Experiment 1: away vs. toward the participant) or size (Experiments 2 and 3: big vs. normal vs. small). The task required participants to decide whether the object was an artifact or a natural object, by pressing or releasing one key. Results showed a facilitation for neutral over dangerous objects in the static situation, probably due to an affordance effect. Instead, in the dynamic condition responses were modulated by the object movement direction, with a dynamic affordance effect elicited by neutral objects and an escape-avoidance effect provoked by dangerous objects (neutral objects were processed faster when they moved toward-approached the participant, whereas dangerous objects were processed faster when they moved away from the participant). Moreover, static stimuli influenced the manual response typology. These data indicate the emergence of dynamic affordance and escaping-avoidance effects. PMID:23847512

Keep away from danger: dangerous objects in dynamic and static situations.

PubMed

Anelli, Filomena; Nicoletti, Roberto; Bolzani, Roberto; Borghi, Anna M

2013-01-01

Behavioral and neuroscience studies have shown that objects observation evokes specific affordances (i.e., action possibilities) and motor responses. Recent findings provide evidence that even dangerous objects can modulate the motor system evoking aversive affordances. This sounds intriguing since so far the majority of behavioral, brain imaging, and transcranial magnetic stimulation studies with painful and dangerous stimuli strictly concerned the domain of pain, with the exception of evidence suggesting sensitivity to objects' affordances when neutral objects are located in participants' peripersonal space. This study investigates whether the observation of a neutral or dangerous object in a static or dynamic situation differently influences motor responses, and the time-course of the dangerous objects' processing. In three experiments we manipulated: object dangerousness (neutral vs. dangerous); object category (artifact vs. natural); manual response typology (press vs. release a key); object presentation (Experiment 1: dynamic, Experiments 2 and 3: static); object movement direction (Experiment 1: away vs. toward the participant) or size (Experiments 2 and 3: big vs. normal vs. small). The task required participants to decide whether the object was an artifact or a natural object, by pressing or releasing one key. Results showed a facilitation for neutral over dangerous objects in the static situation, probably due to an affordance effect. Instead, in the dynamic condition responses were modulated by the object movement direction, with a dynamic affordance effect elicited by neutral objects and an escape-avoidance effect provoked by dangerous objects (neutral objects were processed faster when they moved toward-approached the participant, whereas dangerous objects were processed faster when they moved away from the participant). Moreover, static stimuli influenced the manual response typology. These data indicate the emergence of dynamic affordance and escaping-avoidance effects.

Botulinum Toxin Injections Reduce Associative Plasticity in Patients with Primary Dystonia

PubMed Central

Kojovic, Maja; Caronni, Antonio; Bologna, Matteo; Rothwell, John C.; Bhatia, Kailash P.; Edwards, Mark J.

2014-01-01

Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions. We asked if botulinum toxin injections in dystonia patients might also affect the integrity of sensorimotor cortical plasticity, one of the key pathophysiological features of dystonia. We applied a paired associative stimulation protocol, known to induce long-term potentiation–like changes in the primary motor cortex hand area to 12 patients with cervical dystonia before and 1 and 3 months after botulinum toxin injections to the neck muscles. Primary motor cortex excitability was probed by measuring transcranial magnetic stimulation-evoked motor evoked potentials before and after paired associative stimulation. We also measured the input–output curve, short-interval intracortical inhibition, intracortical facilitation, short afferent inhibition, and long afferent inhibition in hand muscles and the clinical severity of dystonia. Before botulinum toxin injections, paired associative stimulation significantly facilitated motor evoked potentials in hand muscles. One month after injections, this effect was abolished, with partial recovery after 3 months. There were significant positive correlations between the facilitation produced by paired associative stimulation and (1) the time elapsed since botulinum toxin injections and (2) the clinical dystonia score. One effect of botulinum toxin injection treatment is to modulate afferent input from the neck. We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity. PMID:21469207

The efficiency of simultaneous binaural ocular vestibular evoked myogenic potentials: a comparative study with monaural acoustic stimulation in healthy subjects.

PubMed

Kim, Min-Beom; Ban, Jae Ho

2012-12-01

To evaluate the test-retest reliability and convenience of simultaneous binaural acoustic-evoked ocular vestibular evoked myogenic potentials (oVEMP). Thirteen healthy subjects with no history of ear diseases participated in this study. All subjects underwent oVEMP test with both separated monaural acoustic stimulation and simultaneous binaural acoustic stimulation. For evaluating test-retest reliability, three repetitive sessions were performed in each ear for calculating the intraclass correlation coefficient (ICC) for both monaural and binaural tests. We analyzed data from the biphasic n1-p1 complex, such as latency of peak, inter-peak amplitude, and asymmetric ratio of amplitude in both ears. Finally, we checked the total time required to complete each test for evaluating test convenience. No significant difference was observed in amplitude and asymmetric ratio in comparison between monaural and binaural oVEMP. However, latency was slightly delayed in binaural oVEMP. In test-retest reliability analysis, binaural oVEMP showed excellent ICC values ranging from 0.68 to 0.98 in latency, asymmetric ratio, and inter-peak amplitude. Additionally, the test time was shorter in binaural than monaural oVEMP. oVEMP elicited from binaural acoustic stimulation yields similar satisfactory results as monaural stimulation. Further, excellent test-retest reliability and shorter test time were achieved in binaural than in monaural oVEMP.

From cognitive networks to seizures: Stimulus evoked dynamics in a coupled cortical network

NASA Astrophysics Data System (ADS)

Lee, Jaejin; Ermentrout, Bard; Bodner, Mark

2013-12-01

Epilepsy is one of the most common neuropathologies worldwide. Seizures arising in epilepsy or in seizure disorders are characterized generally by uncontrolled spread of excitation and electrical activity to a limited region or even over the entire cortex. While it is generally accepted that abnormal excessive firing and synchronization of neuron populations lead to seizures, little is known about the precise mechanisms underlying human epileptic seizures, the mechanisms of transitions from normal to paroxysmal activity, or about how seizures spread. Further complication arises in that seizures do not occur with a single type of dynamics but as many different phenotypes and genotypes with a range of patterns, synchronous oscillations, and time courses. The concept of preventing, terminating, or modulating seizures and/or paroxysmal activity through stimulation of brain has also received considerable attention. The ability of such stimulation to prevent or modulate such pathological activity may depend on identifiable parameters. In this work, firing rate networks with inhibitory and excitatory populations were modeled. Network parameters were chosen to model normal working memory behaviors. Two different models of cognitive activity were developed. The first model consists of a single network corresponding to a local area of the brain. The second incorporates two networks connected through sparser recurrent excitatory connectivity with transmission delays ranging from approximately 3 ms within local populations to 15 ms between populations residing in different cortical areas. The effect of excitatory stimulation to activate working memory behavior through selective persistent activation of populations is examined in the models, and the conditions and transition mechanisms through which that selective activation breaks down producing spreading paroxysmal activity and seizure states are characterized. Specifically, we determine critical parameters and architectural changes that produce the different seizure dynamics in the networks. This provides possible mechanisms for seizure generation. Because seizures arise as attractors in a multi-state system, the system may possibly be returned to its baseline state through some particular stimulation. The ability of stimulation to terminate seizure dynamics in the local and distributed models is studied. We systematically examine when this may occur and the form of the stimulation necessary for the range of seizure dynamics. In both the local and distributed network models, termination is possible for all seizure types observed by stimulation possessing some particular configuration of spatial and temporal characteristics.

Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report.

PubMed

Hylands-White, Nicholas; Duarte, Rui V; Beeson, Paul; Mayhew, Stephen D; Raphael, Jon H

2016-12-01

Pain is a subjective response that limits assessment. The purpose of this case report was to explore how the objectivity of the electroencephalographic response to thermal stimuli would be affected by concurrent spinal cord stimulation. A patient had been implanted with a spinal cord stimulator for the management of complex regional pain syndrome of both hands for 8 years. Following ethical approval and written informed consent we induced thermal stimuli using the Medoc PATHWAY Pain & Sensory Evaluation System on the right hand of the patient with the spinal cord stimulator switched off and with the spinal cord stimulator switched on. The patient reported a clinically significant reduction in thermal induced pain using the numerical rating scale (71.4 % reduction) with spinal cord stimulator switched on. Analysis of electroencephalogram recordings indicated the occurrence of contact heat evoked potentials (N2-P2) with spinal cord stimulator off, but not with spinal cord stimulator on. This case report suggests that thermal pain can be reduced in complex regional pain syndrome patients with the use of spinal cord stimulation and offers objective validation of the reported outcomes with this treatment.

Control theory-based regulation of hippocampal CA1 nonlinear dynamics.

PubMed

Hsiao, Min-Chi; Song, Dong; Berger, Theodore W

2008-01-01

We are developing a biomimetic electronic neural prosthesis to replace regions of the hippocampal brain area that have been damaged by disease or insult. Our previous study has shown that the VLSI implementation of a CA3 nonlinear dynamic model can functionally replace the CA3 subregion of the hippocampal slice. As a result, the propagation of temporal patterns of activity from DG-->VLSI-->CA1 reproduces the activity observed experimentally in the biological DG-->CA3-->CA1 circuit. In this project, we incorporate an open-loop controller to optimize the output (CA1) response. Specifically, we seek to optimize the stimulation signal to CA1 using a predictive dentate gyrus (DG)-CA1 nonlinear model (i.e., DG-CA1 trajectory model) and a CA1 input-output model (i.e., CA1 plant model), such that the ultimate CA1 response (i.e., desired output) can be first predicted by the DG-CA1 trajectory model and then transformed to the desired stimulation through the inversed CA1 plant model. Lastly, the desired CA1 output is evoked by the estimated optimal stimulation. This study will be the first stage of formulating an integrated modeling-control strategy for the hippocampal neural prosthetic system.

Dynamical entrainment of corticospinal excitability during rhythmic movement observation: a Transcranial Magnetic Stimulation study.

PubMed

Varlet, Manuel; Novembre, Giacomo; Keller, Peter E

2017-06-01

Spontaneous modulations of corticospinal excitability during action observation have been interpreted as evidence for the activation of internal motor representations equivalent to the observed action. Alternatively or complementary to this perspective, growing evidence shows that motor activity during observation of rhythmic movements can be modulated by direct visuomotor couplings and dynamical entrainment. In-phase and anti-phase entrainment spontaneously occur, characterized by cyclic movements proceeding simultaneously in the same (in-phase) or opposite (anti-phase) direction. Here we investigate corticospinal excitability during the observation of vertical oscillations of an index finger using Transcranial Magnetic Stimulation (TMS). Motor-evoked potentials (MEPs) were recorded from participants' flexor and extensor muscles of the right index finger, placed in either a maximal steady flexion or extension position, with stimulations delivered at maximal flexion, maximal extension or mid-trajectory of the observed finger oscillations. Consistent with the occurrence of dynamical motor entrainment, increased and decreased MEP responses - suggesting the facilitation of stable in-phase and anti-phase relations but not an unstable 90° phase relation - were found in participants' flexors. Anti-phase motor facilitation contrasts with the activation of internal motor representation as it involves activity in the motor system opposite from activity required for the execution of the observed movement. These findings demonstrate the relevance of dynamical entrainment theories and methods for understanding spontaneous motor activity in the brain during action observation and the mechanisms underpinning coordinated movements during social interaction. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.

PubMed

Qu, Mei-Hua; Ji, Wan-Sheng; Zhao, Ting-Kun; Fang, Chun-Yan; Mao, Shu-Mei; Gao, Zhi-Qin

2016-02-15

To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.

Properties of synaptic transmission from the reticular formation dorsal to the facial nucleus to trigeminal motoneurons during early postnatal development in rats.

PubMed

Gemba-Nishimura, A; Inoue, T; Nakamura, S; Nakayama, K; Mochizuki, A; Shintani, S; Yoshimura, S

2010-03-31

We previously reported that electrical stimulation of the reticular formation dorsal to the facial nucleus (RdVII) elicited excitatory masseter responses at short latencies and that RdVII neurons were antidromically activated by stimulation of the trigeminal motor nucleus (MoV), suggesting that excitatory premotor neurons targeting the MoV are likely located in the RdVII. We thus examined the properties of synaptic transmission from the RdVII to jaw-closing and jaw-opening motoneurons in horizontal brainstem preparations from developing rats using voltage-sensitive dye, patch-clamp recordings and laser photostimulation. Electrical stimulation of the RdVII evoked optical responses in the MoV. Combined bath application of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV) reduced these optical responses, and addition of the glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline further reduced the remaining responses. Electrical stimulation of the RdVII evoked postsynaptic currents (PSCs) in all 19 masseter motoneurons tested in postnatal day (P)1-4 rats, and application of CNQX and the NMDA receptor antagonist (+/-)-3(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced the PSC amplitudes by more than 50%. In the presence of CNQX and CPP, the GABA(A) receptor antagonist SR95531 further reduced PSC amplitude, and addition of strychnine abolished the remaining PSCs. Photostimulation of the RdVII with caged glutamate also evoked PSCs in masseter motoneurons of P3-4 rats. In P8-11 rats, electrical stimulation of the RdVII also evoked PSCs in all 14 masseter motoneurons tested, and the effects of the antagonists on the PSCs were similar to those in P1-4 rats. On the other hand, RdVII stimulation evoked PSCs in only three of 16 digastric motoneurons tested. These results suggest that both neonatal and juvenile jaw-closing motoneurons receive strong synaptic inputs from the RdVII through activation of glutamate, glycine and GABA(A) receptors, whereas inputs from the RdVII to jaw-opening motoneurons seem to be weak. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Electrically-evoked frequency-following response (EFFR) in the auditory brainstem of guinea pigs.

PubMed

He, Wenxin; Ding, Xiuyong; Zhang, Ruxiang; Chen, Jing; Zhang, Daoxing; Wu, Xihong

2014-01-01

It is still a difficult clinical issue to decide whether a patient is a suitable candidate for a cochlear implant and to plan postoperative rehabilitation, especially for some special cases, such as auditory neuropathy. A partial solution to these problems is to preoperatively evaluate the functional integrity of the auditory neural pathways. For evaluating the strength of phase-locking of auditory neurons, which was not reflected in previous methods using electrically evoked auditory brainstem response (EABR), a new method for recording phase-locking related auditory responses to electrical stimulation, called the electrically evoked frequency-following response (EFFR), was developed and evaluated using guinea pigs. The main objective was to assess feasibility of the method by testing whether the recorded signals reflected auditory neural responses or artifacts. The results showed the following: 1) the recorded signals were evoked by neuron responses rather than by artifact; 2) responses evoked by periodic signals were significantly higher than those evoked by the white noise; 3) the latency of the responses fell in the expected range; 4) the responses decreased significantly after death of the guinea pigs; and 5) the responses decreased significantly when the animal was replaced by an electrical resistance. All of these results suggest the method was valid. Recording obtained using complex tones with a missing fundamental component and using pure tones with various frequencies were consistent with those obtained using acoustic stimulation in previous studies.

Adolescent binge-like alcohol alters sensitivity to acute alcohol effects on dopamine release in the nucleus accumbens of adult rats

PubMed Central

Shnitko, Tatiana A.; Spear, Linda P.; Robinson, Donita L.

2015-01-01

Rationale Early onset of alcohol drinking has been associated with alcohol abuse in adulthood. The neurobiology of this phenomenon is unclear, but mesolimbic dopamine pathways, which are dynamic during adolescence, may play a role. Objectives We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. Methods Rats received intermittent intragastric ethanol, water or nothing during adolescence. In adulthood, electrically-evoked dopamine release and subsequent uptake were measured in the nucleus accumbens core at baseline and after acute challenge of ethanol or saline. Results Adolescent ethanol exposure did not alter basal measures of evoked dopamine release or uptake. Ethanol challenge dose-dependently decreased the amplitude of evoked dopamine release in rats by 30–50% in control groups, as previously reported, but did not alter evoked release in ethanol-exposed animals. To address the mechanism by which ethanol altered dopamine signaling, the evoked signals were modeled to estimate dopamine efflux per impulse and the velocity of the dopamine transporter. Dopamine uptake was slower in all exposure groups after ethanol challenge compared to saline, while dopamine efflux per pulse of electrical stimulation was reduced by ethanol only in ethanol-naive rats. Conclusions The results demonstrate that exposure to binge levels of ethanol during adolescence blunts the effect of ethanol challenge to reduce the amplitude of phasic dopamine release in adulthood. Large dopamine transients may result in more extracellular dopamine after alcohol challenge in adolescent-exposed rats, and may be one mechanism by which alcohol is more reinforcing in people who initiated drinking at an early age. PMID:26487039

Optogenetic noise-photostimulation on the brain increases somatosensory spike firing responses.

PubMed

Huidobro, Nayeli; De la Torre-Valdovinos, Braniff; Mendez, Abraham; Treviño, Mario; Arias-Carrion, Oscar; Chavez, Fermin; Gutierrez, Ranier; Manjarrez, Elias

2018-01-18

We examined whether the optogenetic noise-photostimulation (ONP) of the barrel cortex (BC) of anesthetized Thy1-ChR2-YFP transgenic mice increases the neuronal multiunit-activity response evoked by whisker mechanical stimulation (whisker-evoked MUA). In all transgenic mice, we found that the signal-to-noise ratio (SNR) of such whisker-evoked MUA signals exhibited an inverted U-like shape as a function of the ONP level. Numerical simulations of a ChR2-expressing neuron model qualitatively support our experimental data. These results show that the application of an intermediate intensity of ONP in the brain can increase cortical somatosensory spike responses to whisker protraction. These findings suggest that ONP of the mice-BC could produce improvements in somatosensory perception to whisker stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebellar interaction with the acoustic reflex.

PubMed

Jastreboff, P J

1981-01-01

The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc.

Effect of neck flexion on somatosensory and motor evoked potentials in Hirayama disease.

PubMed

Abraham, A; Gotkine, M; Drory, V E; Blumen, S C

2013-11-15

Hirayama disease (HD) is a rare motor disorder mainly affecting young men, characterized by atrophy and weakness of forearm and hand muscles corresponding to a C7-T1 myotome distribution. The weakness is usually unilateral or asymmetric and progression usually stops within several years. The etiology of HD is not well understood. One hypothesis, mainly based on MRI findings, is that the weakness is a consequence of cervical flexion myelopathy. The aim of this study was to explore the function of corticospinal and ascending somatosensory pathways during neck flexion using evoked responses. 15 men with HD and 7 age-matched control male subjects underwent somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP) studies with the neck in neutral position and fully flexed. SSEP studies included electrical stimulation of median and ulnar nerves at the wrist, and tibial nerve at the ankle with recording over the ipsilateral Erb's point, cervical spine, and contralateral sensory cortex. MEP recordings were obtained by magnetic stimulation of the motor cortex and the cervical lower spinal roots; the evoked responses were recorded from the contralateral thenar and abductor hallucis muscles. MEP recordings demonstrated significant lower amplitudes, and slightly prolonged latencies in HD patients on cervical stimulation, compared to control subjects. During neck flexion, MEP studies also demonstrated a statistically significant drop in mean upper limb amplitude on cervical stimulation in HD patients, as well as in control subjects, although to a lesser degree. In contrast, no significant differences were found in SSEP studies in HD patients compared to control subjects, or between neutral and flexed position in these groups. The study shows a negative effect of cervical flexion on MEP amplitudes in HD patients as well as in control subjects, requiring more studies to investigate its significance. Neck flexion did not have an influence on any SSEP parameters in patients or controls. © 2013 Elsevier B.V. All rights reserved.

Band limited chirp stimulation in vestibular evoked myogenic potentials.

PubMed

Walther, Leif Erik; Cebulla, Mario

2016-10-01

Air conducted vestibular evoked myogenic potentials (VEMP) can be elicited by various low frequency and intense sound stimuli, mainly clicks or short tone bursts (STB). Chirp stimuli are increasingly used in diagnostic audiological evaluations as an effective means to obtain acoustically evoked responses in narrowed or extended frequency ranges. We hypothesized in this study that band limited chirp stimulation, which covers the main sensitivity range of sound sensitive otolithic afferents (around 500 Hz), might be useful for application in cervical and ocular VEMP to air conduction. For this purpose we designed a chirp stimulus ranging 250-1000 Hz (up chirp). The chirp stimulus was delivered with a stimulus intensity of 100 dB nHL in normal subjects (n = 10) and patients with otolith involvement (vestibular neuritis) (n = 6). Amplitudes of the designed chirp ("CW-VEMP-chirp, 250-1000 Hz") were compared with amplitudes of VEMPs evoked by click stimuli (0.1 ms) and a short tone burst (STB, 1-2-1, 8 ms, 500 Hz). CVEMPs and oVEMPs were detectable in 9 of 10 normal individuals. Statistical evaluation in healthy patients revealed significantly larger cVEMP and oVEMP amplitudes for CW-VEMP-chirp (250-1000 Hz) stimuli. CVEMP amplitudes evoked by CW-VEMP-chirp (250-1000 Hz) showed a high stability in comparison with click and STB stimulation. CW-VEMP-chirp (250-1000 Hz) showed abnormal cVEMP and oVEMP amplitudes in patients with vestibular neuritis, with the same properties as click and STB stimulated VEMPs. We conclude that the designed CW-VEMP-chirp (250-1000 Hz) is an effective stimulus which can be further used in VEMP diagnostic. Since a chirp stimulus can be easily varied in its properties, in particular with regard to frequency, this might be a promising tool for further investigations.

Identification of spinal circuits involved in touch-evoked dynamic mechanical pain

PubMed Central

Cheng, Longzhen; Duan, Bo; Huang, Tianwen; Zhang, Yan; Chen, Yangyang; Britz, Olivier; Garcia-Campmany, Lidia; Ren, Xiangyu; Vong, Linh; Lowell, Bradford B.; Goulding, Martyn; Wang, Yun; Ma, Qiufu

2017-01-01

Mechanical hypersensitivity is a debilitating symptom associated with millions of chronic pain patients. It exists in distinct forms, including brush-evoked dynamic and filament-evoked punctate. Here we report that dynamic mechanical hypersensitivity induced by nerve injury or inflammation was compromised in mice with ablation of spinal VT3Lbx1 neurons defined by coexpression of VGLUT3Cre and Lbx1Flpo, as indicated by the loss of brush-evoked nocifensive responses and conditional place aversion. Electrophysiological recordings show that VT3Lbx1 neurons form morphine-resistant polysynaptic pathways relaying inputs from low-threshold Aβ mechanoreceptors to lamina I output neurons. Meanwhile, the subset of somatostatin (SOM) lineage neurons preserved in VT3Lbx1 neuron-ablated mice is largely sufficient to mediate von Frey filament-evoked punctate mechanical hypersensitivity, including both morphine-sensitive and morphine-resistant forms. Furthermore, acute silencing of VT3Lbx1 neurons attenuated pre-established dynamic mechanical hypersensitivity induced by nerve injury, suggesting these neurons as a potential cellular target for treating this form of neuropathic pain. PMID:28436981

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units

PubMed Central

Sanchez, Gabriel N.; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L.; Schnitzer, Mark J.

2017-01-01

SUMMARY Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle’s contractile units. Despite the motor unit’s centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. PMID:26687220

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units.

PubMed

Sanchez, Gabriel N; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L; Schnitzer, Mark J

2015-12-16

Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. Copyright © 2015 Elsevier Inc. All rights reserved.

In vivo correlation between c-Fos expression and corticotroph stimulation by adrenocorticotrophic hormone secretagogues in rat anterior pituitary gland.

PubMed

Takigami, Shu; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

2008-03-01

In the anterior pituitary gland, c-Fos expression is evoked by various stimuli. However, whether c-Fos expression is directly related to the stimulation of anterior pituitary cells by hypothalamic secretagogues is unclear. To confirm whether the reception of hormone-releasing stimuli evokes c-Fos expression in anterior pituitary cells, we have examined c-Fos expression of anterior pituitary glands in rats administered with synthetic corticotrophin-releasing hormone (CRH) intravenously or subjected to restraint stress. Single intravenous administration of CRH increases the number of c-Fos-expressing cells, and this number does not change even if the dose is increased. Double-immunostaining has revealed that most of the c-Fos-expressing cells contain adrenocorticotrophic hormone (ACTH); corticotrophs that do not express c-Fos in response to CRH have also been found. However, restraint stress evokes c-Fos expression in most of the corticotrophs and in a partial population of lactotrophs. These results suggest that c-Fos expression increases in corticotrophs stimulated by ACTH secretagogues, including CRH. Furthermore, we have found restricted numbers of corticotrophs expressing c-Fos in response to CRH. Although the mechanism underlying the different responses to CRH is not apparent, c-Fos is probably a useful immunohistochemical marker for corticotrophs stimulated by ACTH secretagogues.

Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function.

PubMed

Cabib, Christopher; Ortega, Omar; Kumru, Hatice; Palomeras, Ernest; Vilardell, Natalia; Alvarez-Berdugo, Daniel; Muriana, Desirée; Rofes, Laia; Terré, Rosa; Mearin, Fermín; Clavé, Pere

2016-09-01

Oropharyngeal dysphagia (OD) is very prevalent among poststroke patients, causing severe complications but lacking specific neurorehabilitation treatment. This review covers advances in the pathophysiology, diagnosis, and physiologically based neurorehabilitation strategies for poststroke OD. The pathophysiology of oropharyngeal biomechanics can be assessed by videofluoroscopy, as delayed laryngeal vestibule closure is closely associated with aspiration. Stroke may affect afferent or efferent neuronal circuits participating in deglutition. The integrity of oropharyngeal-cortical afferent pathways can be assessed by electroencephalography through sensory-evoked potentials by pharyngeal electrical stimulation, while corticopharyngeal efferent pathways can be characterized by electromyography through motor-evoked potentials by transcranial magnetic stimulation. Dysfunction in both cortico-mediated evoked responses is associated with delayed swallow response and aspiration. Studies have reported hemispherical asymmetry on motor control of swallowing and the relevance of impaired oropharyngeal sensitivity on aspiration. Advances in treatment include improvements in compensatory strategies but are mainly focused on (1) peripheral stimulation strategies and (2) central, noninvasive stimulation strategies with evidence of their clinical benefits. Characterization of poststroke OD is evolving from the assessment of impaired biomechanics to the sensorimotor integration processes involved in deglutition. Treatment is also changing from compensatory strategies to promoting brain plasticity, both to recover swallow function and to improve brain-related swallowing dysfunction. © 2016 New York Academy of Sciences.

Inhibitory effect of the nucleus reticularis pontis oralis on the pontine micturition center and pontine urine storage center in decerebrate cats.

PubMed

Sugaya, Kimio; Nishijima, Saori; Miyazato, Minoru; Oda, Masami; Ogawa, Yoshihide

2006-10-01

The influence of the nucleus reticularis pontis oralis (PoO) on the pontine micturition center (PMC) and pontine urine storage center (PUSC) was examined in decerebrate cats by electrical and chemical stimulations of the PMC, PUSC or PoO. Microinjection of carbachol into the rostral and dorsolateral part of the PoO rapidly inhibited reflex micturition and external urethral sphincter (EUS) activity. After confirming the inhibition of reflex micturition and EUS activity by microinjection of carbachol into the PoO, intravenous injection of atropine sulfate or its microinjection into the PoO recovered both reflex micturition and EUS activity. Microinjection of carbachol into the PMC evoked micturition and then inhibited reflex micturition, but intravenous injection of atropine or its microinjection into the PoO recovered reflex micturition. After confi rming the inhibition of reflex micturition and EUS activity by microinjection of carbachol into the PoO, electrical stimulation of the PUSC enhanced EUS activity, but electrical stimulation of the PMC failed to evoke micturition. However, electrical stimulation of the PMC evoked micturition after microinjection of atropine into the PoO. These results suggest that the PoO strongly inhibits the PMC and less strongly inhibits the PUSC. Therefore, the PoO seems to be the pontine micturition inhibitory area.

Motor evoked responses from the thigh muscles to the stimulation of the upper limb nerves in patients with late poliomyelitis.

PubMed

Ertekin, Cumhur; On, Arzu Yagiz; Kirazli, Yeşim; Kurt, Tülay; Gürgör, Nevin

2002-04-01

To demonstrate a clear-cut M response recorded from the severely affected thigh muscles to the stimulation of the upper limb nerves in a serial of patients with late poliomyelitis. Fifteen patients with late poliomyelitis, 7 patients with spinal cord disorders and 11 control subjects were included. Evoked muscle responses were investigated in quadriceps femoris and/or thigh adductor muscles to the stimulation of the brachial plexus, median and ulnar nerves. Evoked muscle responses were obtained from the thigh muscles in all 12 late polio patients with proximal lower extremity involvement. The response could not be recorded from the thigh muscles neither in the 3 polio patients with upper extremity involvement nor in the healthy control subjects and in patients with other spinal cord disorders of anterior horn cell. It is proposed that the electrical stimulation of the arm nerves produce interlimb descending muscle responses in the severely affected atrophic thigh muscles of the patients with late polio. This finding suggests that there might be a focal and/or specific loss of inhibitory interneurons between injured and normal motor neurons and increased facilitatory synaptic action at the end of long propriospinal descending fibers in the case of late poliomyelitis.

Granger causal time-dependent source connectivity in the somatosensory network

NASA Astrophysics Data System (ADS)

Gao, Lin; Sommerlade, Linda; Coffman, Brian; Zhang, Tongsheng; Stephen, Julia M.; Li, Dichen; Wang, Jue; Grebogi, Celso; Schelter, Bjoern

2015-05-01

Exploration of transient Granger causal interactions in neural sources of electrophysiological activities provides deeper insights into brain information processing mechanisms. However, the underlying neural patterns are confounded by time-dependent dynamics, non-stationarity and observational noise contamination. Here we investigate transient Granger causal interactions using source time-series of somatosensory evoked magnetoencephalographic (MEG) elicited by air puff stimulation of right index finger and recorded using 306-channel MEG from 21 healthy subjects. A new time-varying connectivity approach, combining renormalised partial directed coherence with state space modelling, is employed to estimate fast changing information flow among the sources. Source analysis confirmed that somatosensory evoked MEG was mainly generated from the contralateral primary somatosensory cortex (SI) and bilateral secondary somatosensory cortices (SII). Transient Granger causality shows a serial processing of somatosensory information, 1) from contralateral SI to contralateral SII, 2) from contralateral SI to ipsilateral SII, 3) from contralateral SII to contralateral SI, and 4) from contralateral SII to ipsilateral SII. These results are consistent with established anatomical connectivity between somatosensory regions and previous source modeling results, thereby providing empirical validation of the time-varying connectivity analysis. We argue that the suggested approach provides novel information regarding transient cortical dynamic connectivity, which previous approaches could not assess.

Evoked EMG versus Muscle Torque during Fatiguing Functional Electrical Stimulation-Evoked Muscle Contractions and Short-Term Recovery in Individuals with Spinal Cord Injury

PubMed Central

Estigoni, Eduardo H.; Fornusek, Che; Hamzaid, Nur Azah; Hasnan, Nazirah; Smith, Richard M.; Davis, Glen M.

2014-01-01

This study investigated whether the relationship between muscle torque and m-waves remained constant after short recovery periods, between repeated intervals of isometric muscle contractions induced by functional electrical stimulation (FES). Eight subjects with spinal cord injury (SCI) were recruited for the study. All subjects had their quadriceps muscles group stimulated during three sessions of isometric contractions separated by 5 min of recovery. The evoked-electromyographic (eEMG) signals, as well as the produced torque, were synchronously acquired during the contractions and during short FES bursts applied during the recovery intervals. All analysed m-wave variables changed progressively throughout the three contractions, even though the same muscle torque was generated. The peak to peak amplitude (PtpA), and the m-wave area (Area) were significantly increased, while the time between the stimulus artefact and the positive peak (PosT) were substantially reduced when the muscles became fatigued. In addition, all m-wave variables recovered faster and to a greater extent than did torque after the recovery intervals. We concluded that rapid recovery intervals between FES-evoked exercise sessions can radically interfere in the use of m-waves as a proxy for torque estimation in individuals with SCI. This needs to be further investigated, in addition to seeking a better understanding of the mechanisms of muscle fatigue and recovery. PMID:25479324

Evoked EMG versus muscle torque during fatiguing functional electrical stimulation-evoked muscle contractions and short-term recovery in individuals with spinal cord injury.

PubMed

Estigoni, Eduardo H; Fornusek, Che; Hamzaid, Nur Azah; Hasnan, Nazirah; Smith, Richard M; Davis, Glen M

2014-12-03

This study investigated whether the relationship between muscle torque and m-waves remained constant after short recovery periods, between repeated intervals of isometric muscle contractions induced by functional electrical stimulation (FES). Eight subjects with spinal cord injury (SCI) were recruited for the study. All subjects had their quadriceps muscles group stimulated during three sessions of isometric contractions separated by 5 min of recovery. The evoked-electromyographic (eEMG) signals, as well as the produced torque, were synchronously acquired during the contractions and during short FES bursts applied during the recovery intervals. All analysed m-wave variables changed progressively throughout the three contractions, even though the same muscle torque was generated. The peak to peak amplitude (PtpA), and the m-wave area (Area) were significantly increased, while the time between the stimulus artefact and the positive peak (PosT) were substantially reduced when the muscles became fatigued. In addition, all m-wave variables recovered faster and to a greater extent than did torque after the recovery intervals. We concluded that rapid recovery intervals between FES-evoked exercise sessions can radically interfere in the use of m-waves as a proxy for torque estimation in individuals with SCI. This needs to be further investigated, in addition to seeking a better understanding of the mechanisms of muscle fatigue and recovery.

Neural hijacking: action of high-frequency electrical stimulation on cortical circuits.

PubMed

Cheney, P D; Griffin, D M; Van Acker, G M

2013-10-01

Electrical stimulation of the brain was one of the first experimental methods applied to understanding brain organization and function and it continues as a highly useful method both in research and clinical applications. Intracortical microstimulation (ICMS) involves applying electrical stimuli through a microelectrode suitable for recording the action potentials of single neurons. ICMS can be categorized into single-pulse stimulation; high-frequency, short-duration stimulation; and high-frequency, long-duration stimulation. For clinical and experimental reasons, considerable interest focuses on the mechanism of neural activation by electrical stimuli. In this article, we discuss recent results suggesting that action potentials evoked in cortical neurons by high-frequency electrical stimulation do not sum with the natural, behaviorally related background activity; rather, high-frequency stimulation eliminates and replaces natural activity. We refer to this as neural hijacking. We propose that a major component of the mechanism underlying neural hijacking is excitation of axons by ICMS and elimination of natural spikes by antidromic collision with stimulus-driven spikes evoked at high frequency. Evidence also supports neural hijacking as an important mechanism underlying the action of deep brain stimulation in the subthalamic nucleus and its therapeutic effect in treating Parkinson's disease.

Novel pH-Sensitive Lipid Based Exo-Endocytosis Tracers Reveal Fast Intermixing of Synaptic Vesicle Pools

PubMed Central

Kahms, Martin; Klingauf, Jürgen

2018-01-01

Styryl dyes and genetically encoded pH-sensitive fluorescent proteins like pHluorin are well-established tools for the optical analysis of synaptic vesicle (SV) recycling at presynaptic boutons. Here, we describe the development of a new class of fluorescent probes based on pH-sensitive organic dyes covalently bound to lipids, providing a promising complementary assay to genetically encoded fluorescent probes. These new optical tracers allow a pure read out of membrane turnover during synaptic activity and visualization of multiple rounds of stimulation-dependent SV recycling without genetic perturbation. Measuring the incorporation efficacy of different dye-labeled lipids into budding SVs, we did not observe an enrichment of lipids with affinity for liquid ordered membrane domains. But most importantly, we found no evidence for a static segregation of SVs into recycling and resting pools. A small but significant fraction of SVs that is reluctant to release during a first round of evoked activity can be exocytosed during a second bout of stimulation, showing fast intermixing of SV pools within seconds. Furthermore, we found that SVs recycling spontaneously have a higher chance to re-occupy release sites than SVs recycling during high-frequency evoked activity. In summary, our data provide strong evidence for a highly dynamic and use-dependent control of the fractions of releasable or resting SVs. PMID:29456492

Using Transcranial Magnetic Stimulation to Evaluate the Motor Pathways After an Intraoperative Spinal Cord Injury and to Predict the Recovery of Intraoperative Transcranial Electrical Motor Evoked Potentials: A Case Report.

PubMed

Grover, Helen J; Thornton, Rachel; Lutchman, Lennel N; Blake, Julian C

2016-06-01

The authors report a case of unilateral loss of intraoperative transcranial electrical motor evoked potentials (TES MEP) associated with a spinal cord injury during scoliosis correction and the subsequent use of extraoperative transcranial magnetic stimulation to monitor the recovery of spinal cord function. The authors demonstrate the absence of TES MEPs and absent transcranial magnetic stimulation responses in the immediate postoperative period, and document the partial recovery of transcranial magnetic stimulation responses, which corresponded to partial recovery of TES MEPs. Intraoperative TES MEPs were enhanced using spatial facilitation technique, which enabled the patient to undergo further surgery to stabilize the spine and correct her scoliosis. This case report supports evidence of the use of extraoperative transcranial magnetic stimulation to predict the presence of intraoperative TES responses and demonstrates the usefulness of spatial facilitation to monitor TES MEPs in a patient with a preexisting spinal cord injury.

Basic Hearing and Echolocation Mechanisms of Marine Mammals: Measured Auditory Evoked Potential and Behavioral Experiments FY 2007

DTIC Science & Technology

2007-01-01

Breese, M. (2007) Evoked-potential recovery during double click stimulation in a whale: A possibility of biosonar automatic gain control. Journal of...Yokohama Japan (published) Supin A.Ya, Nachtigall, P.E., and Breese, M. Source level to sensation level ratio of transmitted biosonar pulses in an

Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

ERIC Educational Resources Information Center

Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

2010-01-01

Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

BRAIN CHOLINESTERASE INHIBITION PRODUCED BY PROPOXUR AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS IN LONG EVANS RATS.

EPA Science Inventory

Propoxur is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response following stimulation of the visual system with flashes of light. They ar...

Phase stability analysis of chirp evoked auditory brainstem responses by Gabor frame operators.

PubMed

Corona-Strauss, Farah I; Delb, Wolfgang; Schick, Bernhard; Strauss, Daniel J

2009-12-01

We have recently shown that click evoked auditory brainstem responses (ABRs) can be efficiently processed using a novelty detection paradigm. Here, ABRs as a large-scale reflection of a stimulus locked neuronal group synchronization at the brainstem level are detected as novel instance-novel as compared to the spontaneous activity which does not exhibit a regular stimulus locked synchronization. In this paper we propose for the first time Gabor frame operators as an efficient feature extraction technique for ABR single sweep sequences that is in line with this paradigm. In particular, we use this decomposition technique to derive the Gabor frame phase stability (GFPS) of sweep sequences of click and chirp evoked ABRs. We show that the GFPS of chirp evoked ABRs provides a stable discrimination of the spontaneous activity from stimulations above the hearing threshold with a small number of sweeps, even at low stimulation intensities. It is concluded that the GFPS analysis represents a robust feature extraction method for ABR single sweep sequences. Further studies are necessary to evaluate the value of the presented approach for clinical applications.

Non-provocative diagnostics of photosensitivity using visual evoked potentials.

PubMed

Vermeulen, Joost; Kalitzin, Stiliyan; Parra, Jaime; Dekker, Erwin; Vossepoel, Albert; da Silva, Fernando Lopes

2008-04-01

Photosensitive epilepsy (PSE) is the most common form of reflex epilepsy. Usually, to find out whether a patient is sensitive, he/she is stimulated visually with, e.g. a stroboscopic light stimulus at variable frequency and intensity until a photo paroxysmal response (PPR) occurs. The research described in this work aims to find whether photosensitivity can be detected without provoking a PPR. Twenty-two subjects, 15 with known photosensitivity, were stimulated with visual stimuli that did not provoke a PPR. Using an "evoked response representation", 18 features were analytically derived from EEG signals. Single- and multi-feature classification paradigms were applied to extract those features that separate best subjects with PSE from controls. Two variables in the "evoked response representation", a frequency term and a goodness of fit term to a particular template, appeared to be best suited to make a prediction about the photosensitivity of a subject. Evoked responses appear to carry information about potential PSE. This result can be useful for screening patients for photosensitivity and it may also help to assess in a quantitative way the effectiveness of medical therapy.

The Effectiveness of FES-Evoked EMG Potentials to Assess Muscle Force and Fatigue in Individuals with Spinal Cord Injury

PubMed Central

Ibitoye, Morufu Olusola; Estigoni, Eduardo H.; Hamzaid, Nur Azah; Wahab, Ahmad Khairi Abdul; Davis, Glen M.

2014-01-01

The evoked electromyographic signal (eEMG) potential is the standard index used to monitor both electrical changes within the motor unit during muscular activity and the electrical patterns during evoked contraction. However, technical and physiological limitations often preclude the acquisition and analysis of the signal especially during functional electrical stimulation (FES)-evoked contractions. Hence, an accurate quantification of the relationship between the eEMG potential and FES-evoked muscle response remains elusive and continues to attract the attention of researchers due to its potential application in the fields of biomechanics, muscle physiology, and rehabilitation science. We conducted a systematic review to examine the effectiveness of eEMG potentials to assess muscle force and fatigue, particularly as a biofeedback descriptor of FES-evoked contractions in individuals with spinal cord injury. At the outset, 2867 citations were identified and, finally, fifty-nine trials met the inclusion criteria. Four hypotheses were proposed and evaluated to inform this review. The results showed that eEMG is effective at quantifying muscle force and fatigue during isometric contraction, but may not be effective during dynamic contractions including cycling and stepping. Positive correlation of up to r = 0.90 (p < 0.05) between the decline in the peak-to-peak amplitude of the eEMG and the decline in the force output during fatiguing isometric contractions has been reported. In the available prediction models, the performance index of the eEMG signal to estimate the generated muscle force ranged from 3.8% to 34% for 18 s to 70 s ahead of the actual muscle force generation. The strength and inherent limitations of the eEMG signal to assess muscle force and fatigue were evident from our findings with implications in clinical management of spinal cord injury (SCI) population. PMID:25025551

Visual evoked potentials in patients after methanol poisoning.

PubMed

Urban, Pavel; Zakharov, Sergey; Diblík, Pavel; Pelclová, Daniela; Ridzoň, Petr

2016-01-01

We report the results of the visual evoked potentials (VEP) examination in patients after severe poisoning by methanol. The group of 47 patients (38 males and 9 females) was assembled out of persons who survived an outbreak of poisoning by the methanol adulterated alcohol beverages, which happened in the Czech Republic in 2012-2013. The visual evoked potentials examination was performed using monocular checkerboard pattern-reversal stimulation. Two criteria of abnormality were chosen: missing evoked response, and wave P1 latency > 117 ms. Non-parametric statistical methods (median, range, and the median test) were used to analyze factors influencing the VEP abnormality. The visual evoked potential was abnormal in 20 patients (43%), 5 of them had normal visual acuity on the Snellen chart. The VEP abnormality did not correlate significantly with initial serum concentrations of methanol, formic acid or lactate; however, it showed statistically significant inverse relation to the initial serum pH: the subgroup with the abnormal VEP had significantly lower median pH in comparison with the subgroup with the normal VEP (7.16 vs. 7.34, p = 0.04). The abnormality was not related to chronic alcohol abuse. The visual evoked potentials examination appeared sensitive enough to detected even subclinical impairment of the optic system. Metabolic acidosis is likely to be the key factor related to the development of visual damage induced by methanol. The examination performed with a delay of 1-9 months after the poisoning documented the situation relatively early after the event. It is considered as a baseline for the planned long-term follow-up of the patients, which will make it possible to assess the dynamics of the observed changes, their reversibility, and the occurrence of potential late sequelae. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Don't forget the lyrics! Spatiotemporal dynamics of neural mechanisms spontaneously evoked by gaps of silence in familiar and newly learned songs.

PubMed

Gabriel, Damien; Wong, Thian Chiew; Nicolier, Magali; Giustiniani, Julie; Mignot, Coralie; Noiret, Nicolas; Monnin, Julie; Magnin, Eloi; Pazart, Lionel; Moulin, Thierry; Haffen, Emmanuel; Vandel, Pierre

2016-07-01

The vast majority of people experience musical imagery, the sensation of reliving a song in absence of any external stimulation. Internal perception of a song can be deliberate and effortful, but also may occur involuntarily and spontaneously. Moreover, musical imagery is also involuntarily used for automatically completing missing parts of music or lyrics from a familiar song. The aim of our study was to explore the onset of musical imagery dynamics that leads to the automatic completion of missing lyrics. High-density electroencephalography was used to record the cerebral activity of twenty healthy volunteers while they were passively listening to unfamiliar songs, very familiar songs, and songs previously listened to for two weeks. Silent gaps inserted into these songs elicited a series of neural activations encompassing perceptual, attentional and cognitive mechanisms (range 100-500ms). Familiarity and learning effects emerged as early as 100ms and lasted 400ms after silence occurred. Although participants reported more easily mentally imagining lyrics in familiar rather than passively learnt songs, the onset of neural mechanisms and the power spectrum underlying musical imagery were similar for both types of songs. This study offers new insights into the musical imagery dynamics evoked by gaps of silence and on the role of familiarity and learning processes in the generation of these dynamics. The automatic and effortless method presented here is a potentially useful tool to understand failure in the familiarity and learning processes of pathological populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Dynamics of Multistable States during Ongoing and Evoked Cortical Activity

PubMed Central

Mazzucato, Luca

2015-01-01

Single-trial analyses of ensemble activity in alert animals demonstrate that cortical circuits dynamics evolve through temporal sequences of metastable states. Metastability has been studied for its potential role in sensory coding, memory, and decision-making. Yet, very little is known about the network mechanisms responsible for its genesis. It is often assumed that the onset of state sequences is triggered by an external stimulus. Here we show that state sequences can be observed also in the absence of overt sensory stimulation. Analysis of multielectrode recordings from the gustatory cortex of alert rats revealed ongoing sequences of states, where single neurons spontaneously attain several firing rates across different states. This single-neuron multistability represents a challenge to existing spiking network models, where typically each neuron is at most bistable. We present a recurrent spiking network model that accounts for both the spontaneous generation of state sequences and the multistability in single-neuron firing rates. Each state results from the activation of neural clusters with potentiated intracluster connections, with the firing rate in each cluster depending on the number of active clusters. Simulations show that the model's ensemble activity hops among the different states, reproducing the ongoing dynamics observed in the data. When probed with external stimuli, the model predicts the quenching of single-neuron multistability into bistability and the reduction of trial-by-trial variability. Both predictions were confirmed in the data. Together, these results provide a theoretical framework that captures both ongoing and evoked network dynamics in a single mechanistic model. PMID:26019337

Suppression of bulboreticular unit responses to noxious stimuli by analgesic mesencephalic stimulation.

PubMed

Morrow, T J; Casey, K L

1983-01-01

The responses of 302 neurons in the medial medullary reticular formation (MRF) to a variety of noxious and innocuous somatic stimuli were studied in anesthetized and awake rats. In addition, the effects of analgesic electrical stimulation in the mesencephalon (MES) on unit responses were examined. Tail shock was the most effective stimulus, exciting more than 80% of all units recorded. This stimulus was considered separately during data analysis, since it could not be classified as noxious or innocuous. Noxious somatic stimuli (including pinch, firm pressure, pin prick, and radiant heating of the tail above 45 degrees C were especially effective in eliciting discharge in a significant fraction of all cells in both awake (123/205) and anesthetized (45/97) animals. Nociceptive neurons could be classified as nociceptive specific (NS) or wide dynamic range (WDR) depending on their responses to all somatic stimuli tested. Nociceptive neurons showed no preferential anatomical distribution. Most neurons, including those responsive to noxious inputs, exhibited large, often bilateral receptive fields which frequently covered the tail, one or more limbs, and extensive areas of the body or head. Electrical stimulation within or adjacent to the mesencephalic periaqueductal gray matter depressed the spontaneous and evoked discharge of MRF neurons in both acute and chronic preparations. This inhibition showed a significant preference (p less than 0.001, chi-square statistic) for units that were excited by somatic and especially noxious stimuli. No units were facilitated by MES stimulation. In the awake rat, unit suppression closely followed the time course and level of MES-induced analgesia. Excitability data from the acute experiments suggest that this response inhibition may be the result of a direct action on MRF neurons. Anesthesia severely depressed the spontaneous discharge of MRF neurons as well as the activity evoked by innocuous somatic stimulation. Our data suggest that analgesia produced by MES stimulation is at least in part due to the depression of MRF unit activity, and support the hypothesis that MRF neurons play a critical role in the mediation of behavioral responses to noxious stimuli.

Transcutaneous Electrical Nerve Stimulation Effects on Neglect: A Visual-Evoked Potential Study

PubMed Central

Pitzalis, Sabrina; Spinelli, Donatella; Vallar, Giuseppe; Di Russo, Francesco

2013-01-01

We studied the effects of transcutaneous electrical nerve stimulation (TENS) in six right-brain-damaged patients with left unilateral spatial neglect (USN), using both standard clinical tests (reading, line, and letter cancelation, and line bisection), and electrophysiological measures (steady-state visual-evoked potentials, SSVEP). TENS was applied on left neck muscles for 15′, and measures were recorded before, immediately after, and 60′ after stimulation. Behavioral results showed that the stimulation temporarily improved the deficit in all patients. In cancelation tasks, omissions and performance asymmetries between the two hand-sides were reduced, as well as the rightward deviation in line bisection. Before TENS, SSVEP average latency to stimuli displayed in the left visual half-field [LVF (160 ms)] was remarkably longer than to stimuli shown in the right visual half-field [RVF (120 ms)]. Immediately after TENS, latency to LVF stimuli was 130 ms; 1 h after stimulation the effect of TENS faded, with latency returning to baseline. TENS similarly affected also the latency SSVEP of 12 healthy participants, and their line bisection performance, with effects smaller in size. The present study, first, replicates evidence concerning the positive behavioral effects of TENS on the manifestations of left USN in right-brain-damaged patients; second, it shows putatively related electrophysiological effects on the SSVEP latency. These behavioral and novel electrophysiological results are discussed in terms of specific directional effects of left somatosensory stimulation on egocentric coordinates, which in USN patients are displaced toward the side of the cerebral lesion. Showing that visual-evoked potentials latency is modulated by proprioceptive stimulation, we provide electrophysiological evidence to the effect that TENS may improve some manifestations of USN, with implications for its rehabilitation. PMID:23966919

Age-related changes in laser-evoked potentials following trigeminal and hand stimulation in healthy subjects.

PubMed

de Tommaso, M; Ricci, K; Montemurno, A; Vecchio, E

2017-07-01

This study aimed to evaluate age-related changes in laser-evoked potential (LEP) features, including habituation, via trigeminal and hand stimulation in a large group of healthy volunteers. We recorded the LEPs by right-hand stimulation in 237 healthy subjects and by stimulation of the right supraorbital zone in 170 cases. The subjects ranged in age from 7 to 72 years and were divided into six groups by age. At the trigeminal level, the N2 and P2 latencies were significantly shorter and the N2-P2 amplitude was significantly larger in the 7-17 age group than in the other groups. The N2-P2 amplitude of the responses evoked by hand stimulation was significantly larger in the 7-40 age range than in the older subjects. The N1 amplitude and latency were not significantly different among the groups. The N2-P2 habituation increased with age, but no significant changes among groups were revealed by the Bonferroni test. Trigeminal vertex LEPs have greater amplitudes and appear earlier in children, while a progressive age-related amplitude decrease characterizes the N2-P2 waves associated with hand stimulation. The N2-P2 habituation increases in older people. The N1 latency and amplitude seem to remain stable during ageing and are therefore potentially reliable and useful patterns for nociceptive system examination. Standardization of age-related changes in trigeminal and hand LEPs is possible and should improve their reliability in the objective assessment of pain pathways. © 2017 European Pain Federation - EFIC®.

Parasympathetic reflex vasodilation in the cerebral hemodynamics of rats.

PubMed

Ishii, Hisayoshi; Sato, Toshiya; Izumi, Hiroshi

2014-04-01

We investigated the role of parasympathetic reflex vasodilation in the regulation of the cerebral hemodynamics, and whether GABAA receptors modulate the response. We examined the effects of activation of the parasympathetic fibers through trigeminal afferent inputs on blood flow in the internal carotid artery (ICABF) and the cerebral blood vessels (rCBF) in parietal cortex in urethane-anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited intensity- and frequency-dependent increases in ICABF that were independent of changes in external carotid artery blood flow. Increases in ICABF were elicited by LN stimulation regardless of the presence or absence of sympathetic innervation. The ICABF increases evoked by LN stimulation were almost abolished by the intravenous administration of hexamethonium (10 mg kg(-1)) and were reduced significantly by atropine administration (0.1 mg kg(-1)). Although the LN stimulation alone had no significant effect on rCBF, LN stimulation in combination with a blocker of the GABAA receptor pentylenetetrazole increased the rCBF markedly. This increase in rCBF was reduced significantly by the administration of hexamethonium and atropine. These observations indicate that the increases in both ICABF and rCBF are evoked by parasympathetic activation via the trigeminal-mediated reflex. The rCBF increase evoked by LN stimulation is thought to be limited by the GABAA receptors in the central nervous system. These results suggest that the parasympathetic reflex vasodilation and its modulation mediated by GABA receptors within synaptic transmission in the brainstem are involved in the regulation of the cerebral hemodynamics during trigeminal afferent inputs.

Modulation of Neurally Mediated Vasodepression and Bradycardia by Electroacupuncture through Opioids in Nucleus Tractus Solitarius.

PubMed

Tjen-A-Looi, Stephanie C; Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

2018-01-30

Stimulation of vagal afferent endings with intravenous phenylbiguanide (PBG) causes both bradycardia and vasodepression, simulating neurally mediated syncope. Activation of µ-opioid receptors in the nucleus tractus solitarius (NTS) increases blood pressure. Electroacupuncture (EA) stimulation of somatosensory nerves underneath acupoints P5-6, ST36-37, LI6-7 or G37-39 selectively but differentially modulates sympathoexcitatory responses. We therefore hypothesized that EA-stimulation at P5-6 or ST36-37, but not LI6-7 or G37-39 acupoints, inhibits the bradycardia and vasodepression through a µ-opioid receptor mechanism in the NTS. We observed that stimulation at acupoints P5-6 and ST36-37 overlying the deep somatosensory nerves and LI6-7 and G37-39 overlying cutaneous nerves differentially evoked NTS neural activity in anesthetized and ventilated animals. Thirty-min of EA-stimulation at P5-6 or ST36-37 reduced the depressor and bradycardia responses to PBG while EA at LI6-7 or G37-39 did not. Congruent with the hemodynamic responses, EA at P5-6 and ST36-37, but not at LI6-7 and G37-39, reduced vagally evoked activity of cardiovascular NTS cells. Finally, opioid receptor blockade in the NTS with naloxone or a specific μ-receptor antagonist reversed P5-6 EA-inhibition of the depressor, bradycardia and vagally evoked NTS activity. These data suggest that point specific EA stimulation inhibits PBG-induced vasodepression and bradycardia responses through a μ-opioid mechanism in the NTS.

Peripheral functional organisation of vagally evoked gastric motor responses in the ferret.

PubMed Central

Andrews, P L; Lawes, I N; Bower, A J

1980-01-01

The aims of the present study were to determine the relative amplitudes of intragastric motor responses evoked by different vagal branches and to establish whether the effects of acute or chronic vagotomy could be predicted from these data. Intragastric pressure responses to electrical stimulation of the vagus were measured in urethane-anaesthetised ferrets and acute or chronic vagotomies were performed. The results show that the left and right cervical vagi were equipotential and fully overlaped each other. Their contributions to the dorsal trunk were equipotential and fully overlapping and so were their contributions to the ventral trunk. The dorsal trunk was more effective than the ventral trunk and there was total functional overlap between these two trunks. Vagal evoked gastric motor responses of the ferret are apparently organised in a different way from vagally induced acid secretion or hormone release in the cat. Acute removal of a trunk led to a reduction in evoked responses that was not linear function of the effect of stimulation of that trunk. In contrast, chronic removal caused a relative increase in evoked responses that ws inversely related to the decrease caused by acute removal. The implications of total functional overlap and neuromuscular reorganisation after chronic vagotomy are discussed. PMID:7439800

Evaluation of afferent pain pathways in adrenomyeloneuropathic patients.

PubMed

Yagüe, Sara; Veciana, Misericordia; Casasnovas, Carlos; Ruiz, Montserrat; Pedro, Jordi; Valls-Solé, Josep; Pujol, Aurora

2018-03-01

Patients with adrenomyeloneuropathy may have dysfunctions of visual, auditory, motor and somatosensory pathways. We thought on examining the nociceptive pathways by means of laser evoked potentials (LEPs), to obtain additional information on the pathophysiology of this condition. In 13 adrenomyeloneuropathic patients we examined LEPs to leg, arm and face stimulation. Normative data were obtained from 10 healthy subjects examined in the same experimental conditions. We also examined brainstem auditory evoked potentials (BAEPs), pattern reversal full-field visual evoked potentials (VEPs), motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs). Upper and lower limb MEPs and SEPs, as well as BAEPs, were abnormal in all patients, while VEPs were abnormal in 3 of them (23.1%). LEPs revealed abnormalities to stimulation of the face in 4 patients (30.7%), the forearm in 4 patients (30.7%) and the leg in 10 patients (76.9%). The pathologic process of adrenomyeloneuropathy is characterized by a preferential involvement of auditory, motor and somatosensory tracts and less severely of the visual and nociceptive pathways. This non-inflammatory distal axonopathy preferably damages large myelinated spinal tracts but there is also partial involvement of small myelinated fibres. LEPs studies can provide relevant information about afferent pain pathways involvement in adrenomyeloneuropathic patients. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

PubMed

Sato, Masaki; Ogura, Kazuhiro; Kimura, Maki; Nishi, Koichi; Ando, Masayuki; Tazaki, Masakazu; Shibukawa, Yoshiyuki

2018-06-01

Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X 3 ), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B 4 -negative medium-sized neurons. Action potentials in these isolectin B 4 -negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X 3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X 3 receptors induced an action potential in the Aδ neurons, underlying a sensory generation mechanism of dentinal pain. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography.

PubMed

Harrison, Thomas C; Ayling, Oliver G S; Murphy, Timothy H

2012-04-26

Cortical motor maps are the basis of voluntary movement, but they have proven difficult to understand in the context of their underlying neuronal circuits. We applied light-based motor mapping of Channelrhodopsin-2 mice to reveal a functional subdivision of the forelimb motor cortex based on the direction of movement evoked by brief (10 ms) pulses. Prolonged trains of electrical or optogenetic stimulation (100-500 ms) targeted to anterior or posterior subregions of motor cortex evoked reproducible complex movements of the forelimb to distinct positions in space. Blocking excitatory cortical synaptic transmission did not abolish basic motor map topography, but the site-specific expression of complex movements was lost. Our data suggest that the topography of movement maps arises from their segregated output projections, whereas complex movements evoked by prolonged stimulation require intracortical synaptic transmission. Copyright © 2012 Elsevier Inc. All rights reserved.

What Makes the Muscle Twitch: Motor System Connectivity and TMS-Induced Activity.

PubMed

Volz, Lukas J; Hamada, Masashi; Rothwell, John C; Grefkes, Christian

2015-09-01

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) evokes several volleys of corticospinal activity. While the earliest wave (D-wave) originates from axonal activation of cortico-spinal neurons (CSN), later waves (I-waves) result from activation of mono- and polysynaptic inputs to CSNs. Different coil orientations preferentially stimulate cortical elements evoking different outputs: latero-medial-induced current (LM) elicits D-waves and short-latency electromyographic responses (MEPs); posterior-anterior current (PA) evokes early I-waves. Anterior-posterior current (AP) is more variable and tends to recruit later I-waves, featuring longer onset latencies compared with PA-TMS. We tested whether the variability in response to AP-TMS was related to functional connectivity of the stimulated M1 in 20 right-handed healthy subjects who underwent functional magnetic resonance imaging while performing an isometric contraction task. The MEP-latency after AP-TMS (relative to LM-TMS) was strongly correlated with functional connectivity between the stimulated M1 and a network involving cortical premotor areas. This indicates that stronger premotor-M1 connectivity increases the probability that AP-TMS recruits shorter latency input to CSNs. In conclusion, our data strongly support the hypothesis that TMS of M1 activates distinct neuronal pathways depending on the orientation of the stimulation coil. Particularly, AP currents seem to recruit short latency cortico-cortical projections from premotor areas. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Optical responses evoked by white matter stimulation in rat visual cortical slices and their relation to neural activities.

PubMed

Tanifuji, M; Yamanaka, A; Sunaba, R; Terakawa, S; Toyama, K

1996-10-28

To characterize optical responses (ORs) evoked by white matter (WM) stimulation in slices of rat visual cortex (VC) stained with voltage sensitive dyes, time course of ORs in each layer was investigated by recording ORs with a linearly aligned photodiode array, and the spatial patterns of the ORs at specified time after stimulation were investigated by a CCD camera in combination with stroboscopic illumination. The ORs recorded by the photodiode array were an increase in absorption at 700 nm and a decrease in the wavelength below 650 nm, suggesting that the ORs were dye related. The ORs were compared with field potentials (FPs) to clarify that neural events were represented by the ORs, and in support of this view, we found that the first order spatial differentials of ORs and that of FPs were in good agreement. We further compared ORs with intracellular responses, and found that the ORs mainly represent postsynaptic potentials (PSPs) of VC neurons except for the deeper part of layer VI, where a component representing action potentials in fibers stimulated directly was observed. The time-lapse imaging of ORs showed that excitation first propagated vertically up to layer I and subsequently in the horizontal direction along layers II-III and V-VI as in previous investigations. Spatio-temporal patterns of ORs under blockade of synaptic transmission were also investigated to reveal activity of fibers evoked by WM stimulation which produced such patterns of propagation.

Potentiation by choline of basal and electrically evoked acetylcholine release, as studied using a novel device which both stimulates and perfuses rat corpus striatum

NASA Technical Reports Server (NTRS)

Farber, S. A.; Kischka, U.; Marshall, D. L.; Wurtman, R. J.

1993-01-01

We examined the release of acetylcholine (ACh) and dopamine (DA) using a novel probe through which striatal neurons could be both superfused and stimulated electrically in both anesthetized and freely moving awake animals. Optimal stimulation parameters for eliciting ACh release from cholinergic neurons differed from those required for eliciting DA release from dopaminergic terminals: at 0.6 ms pulse duration, 20 Hz and 200 microA, ACh release increased to 357 +/- 30% (P < 0.01) of baseline and was blocked by the addition of tetrodotoxin (TTX). Pulse durations of 2.0 ms or greater were required to increase DA release. Unlike ACh release, DA release showed no frequency dependence above 5 Hz. The maximal evoked releases of ACh and DA were 556 +/- 94% (P < 0.01) and 254 +/- 38% (P < 0.05) of baseline, respectively. Peripheral administration of choline (Ch) chloride (30-120 mg/kg) to anesthetized animals caused dose-related (r = 0.994, P < 0.01) increases in ACh release; basal release rose from 117 +/- 7% to 141 +/- 5% of initial baseline levels (P < 0.05) and electrically evoked ACh release rose from 386 +/- 38% to 600 +/- 34% (P < 0.01) in rats given 120 mg/kg. However, Ch failed to affect basal or evoked DA release although neostigmine (10 microM) significantly elevated basal DA release (from 36.7 fmol/10 min to 71.5 fmol/10 min; P < 0.05). In awake animals, Ch (120 mg/kg) also elevated both basal (from 106 +/- 7% to 154 +/- 17%; P < 0.05) and electrically evoked (from 146 +/- 13 to 262 +/- 16%; P < 0.01) ACh release.(ABSTRACT TRUNCATED AT 250 WORDS).

Electrical stimulation induces IL-6 in skeletal muscle through extracellular ATP by activating Ca(2+) signals and an IL-6 autocrine loop.

PubMed

Bustamante, Mario; Fernández-Verdejo, Rodrigo; Jaimovich, Enrique; Buvinic, Sonja

2014-04-15

Interleukin-6 (IL-6) is an important myokine that is highly expressed in skeletal muscle cells upon exercise. We assessed IL-6 expression in response to electrical stimulation (ES) or extracellular ATP as a known mediator of the excitation-transcription mechanism in skeletal muscle. We examined whether the canonical signaling cascade downstream of IL-6 (IL-6/JAK2/STAT3) also responds to muscle cell excitation, concluding that IL-6 influences its own expression through a positive loop. Either ES or exogenous ATP (100 μM) increased both IL-6 expression and p-STAT3 levels in rat myotubes, a process inhibited by 100 μM suramin and 2 U/ml apyrase. ATP also evoked IL-6 expression in both isolated skeletal fibers and extracts derived from whole FDB muscles. ATP increased IL-6 release up to 10-fold. STAT3 activation evoked by ATP was abolished by the JAK2 inhibitor HBC. Blockade of secreted IL-6 with a neutralizing antibody or preincubation with the STAT3 inhibitor VIII reduced STAT3 activation evoked by extracellular ATP by 70%. Inhibitor VIII also reduced by 70% IL-6 expression evoked by ATP, suggesting a positive IL-6 loop. In addition, ATP increased up to 60% the protein levels of SOCS3, a negative regulator of the IL-6 signaling pathway. On the other hand, intracellular calcium chelation or blockade of IP3-dependent calcium signals abolished STAT3 phosphorylation evoked by either extracellular ATP or ES. These results suggest that expression of IL-6 in stimulated skeletal muscle cells is mediated by extracellular ATP and nucleotide receptors, involving IP3-dependent calcium signals as an early step that triggers a positive IL-6 autocrine loop.

The area postrema (AP) and the parabrachial nucleus (PBN) are important sites for salmon calcitonin (sCT) to decrease evoked phasic dopamine release in the nucleus accumbens (NAc).

PubMed

Whiting, Lynda; McCutcheon, James E; Boyle, Christina N; Roitman, Mitchell F; Lutz, Thomas A

2017-07-01

The pancreatic hormone amylin and its agonist salmon calcitonin (sCT) act via the area postrema (AP) and the lateral parabrachial nucleus (PBN) to reduce food intake. Investigations of amylin and sCT signaling in the ventral tegmental area (VTA) and nucleus accumbens (NAc) suggest that the eating inhibitory effect of amylin is, in part, mediated through the mesolimbic 'reward' pathway. Indeed, administration of the sCT directly to the VTA decreased phasic dopamine release (DA) in the NAc. However, it is not known if peripheral amylin modulates the mesolimbic system directly or whether this occurs via the AP and PBN. To determine whether and how peripheral amylin or sCT affect mesolimbic reward circuitry we utilized fast scan cyclic voltammetry under anesthesia to measure phasic DA release in the NAc evoked by electrical stimulation of the VTA in intact, AP lesioned and bilaterally PBN lesioned rats. Amylin (50μg/kg i.p.) did not change phasic DA responses compared to saline control rats. However, sCT (50μg/kg i.p.) decreased evoked DA release to VTA-stimulation over 1h compared to saline treated control rats. Further investigations determined that AP and bilateral PBN lesions abolished the ability of sCT to suppress evoked phasic DA responses to VTA-stimulation. These findings implicate the AP and the PBN as important sites for peripheral sCT to decrease evoked DA release in the NAc and suggest that these nuclei may influence hedonic and motivational processes to modulate food intake. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective inhibition of histamine-evoked Ca2+ signals by compartmentalized cAMP in human bronchial airway smooth muscle cells.

PubMed

Dale, Philippa; Head, Victoria; Dowling, Mark R; Taylor, Colin W

2018-05-01

Intracellular Ca 2+ and cAMP typically cause opposing effects on airway smooth muscle contraction. Receptors that stimulate these pathways are therapeutic targets in asthma and chronic obstructive pulmonary disease. However, the interactions between different G protein-coupled receptors (GPCRs) that evoke cAMP and Ca 2+ signals in human bronchial airway smooth muscle cells (hBASMCs) are poorly understood. We measured Ca 2+ signals in cultures of fluo-4-loaded hBASMCs alongside measurements of intracellular cAMP using mass spectrometry or [ 3 H]-adenine labeling. Interactions between the signaling pathways were examined using selective ligands of GPCRs, and inhibitors of Ca 2+ and cAMP signaling pathways. Histamine stimulated Ca 2+ release through inositol 1,4,5-trisphosphate (IP 3 ) receptors in hBASMCs. β 2 -adrenoceptors, through cAMP and protein kinase A (PKA), substantially inhibited histamine-evoked Ca 2+ signals. Responses to other Ca 2+ -mobilizing stimuli were unaffected by cAMP (carbachol and bradykinin) or minimally affected (lysophosphatidic acid). Prostaglandin E 2 (PGE 2 ), through EP 2 and EP 4 receptors, stimulated formation of cAMP and inhibited histamine-evoked Ca 2+ signals. There was no consistent relationship between the inhibition of Ca 2+ signals and the amounts of intracellular cAMP produced by different stimuli. We conclude that β-adrenoceptors, EP 2 and EP 4 receptors, through cAMP and PKA, selectively inhibit Ca 2+ signals evoked by histamine in hBASMCs, suggesting that PKA inhibits an early step in H 1 receptor signaling. Local delivery of cAMP within hyperactive signaling junctions mediates the inhibition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Noxious lingual stimulation influences the excitability of the face primary motor cerebral cortex (face MI) in the rat.

PubMed

Adachi, K; Murray, G M; Lee, J-C; Sessle, B J

2008-09-01

The mechanisms whereby orofacial pain affects motor function are poorly understood. The aims were to determine whether 1) lingual algesic chemical stimulation affected face primary motor cerebral cortex (face MI) excitability defined by intracortical microstimulation (ICMS); and 2) any such effects were limited to the motor efferent MI zones driving muscles in the vicinity of the noxious stimulus. Ketamine-anesthetized Sprague-Dawley male rats were implanted with electromyographic (EMG) electrodes into anterior digastric, masseter, and genioglossus muscles. In 38 rats, three microelectrodes were located in left face MI at ICMS-defined sites for evoking digastric and/or genioglossus responses. ICMS thresholds for evoking EMG activity from each site were determined every 15 min for 1 h, then the right anterior tongue was infused (20 microl, 120 microl/h) with glutamate (1.0 M, n = 18) or isotonic saline (n = 7). Subsequently, ICMS thresholds were determined every 15 min for 4 h. In intact control rats (n = 13), ICMS thresholds were recorded over 5 h. Only left and right genioglossus ICMS thresholds were significantly increased (< or =350%) in the glutamate infusion group compared with intact and isotonic saline groups (P < 0.05). These dramatic effects of glutamate on ICMS-evoked genioglossus activity contrast with its weak effects only on right genioglossus activity evoked from the internal capsule or hypoglossal nucleus. This is the first documentation that intraoral noxious stimulation results in prolonged neuroplastic changes manifested as a decrease in face MI excitability. These changes appear to occur predominantly in those parts of face MI that provide motor output to the orofacial region receiving the noxious stimulation.

A short latency vestibular evoked potential (VsEP) produced by bone-conducted acoustic stimulation

NASA Astrophysics Data System (ADS)

McAngus Todd, Neil P.; Rosengren, Sally M.; Colebatch, James G.

2003-12-01

In this paper data are presented from an experiment which provides evidence for the existence of a short latency, acoustically evoked potential of probable vestibular origin. The experiment was conducted in two phases using bone-conducted acoustic stimulation. In the first phase subjects were stimulated with 6-ms, 500-Hz tone bursts in order to obtain the threshold VT for vestibular evoked myogenic potentials (VEMP). It was confirmed that the difference between bone-conducted auditory and acoustic vestibular thresholds was slightly over 30 dB. The estimated threshold was then used as a reference value in the second part of the experiment to stimulate subjects over a range of intensities from -6 to +18 dB (re:VT). Averaged EEG recordings were made with eight Ag/AgCl electrodes placed on the scalp at Fpz, F3, F4, F7, F8, Cz, T3, and T4 according to the 10-20 system. Below VT auditory midlatency responses (MLRs) were observed. Above VT two additional potentials appeared: a positivity at about 10 ms (P10) which was maximal at Cz, and a negativity at about 15 ms (N15) which was maximal at Fpz. Extrapolation of the growth functions for the P10 and N15 indicated a threshold close to VT, consistent with a vestibular origin of these potentials. Given the low threshold of vestibular acoustic sensitivity it is possible that this mode may make a contribution to the detection of and affective responses to loud low frequency sounds. The evoked potentials may also have application as a noninvasive and nontraumatic test of vestibular projections to the cortex.

Handedness-related asymmetry in transmission in a system of human cervical premotoneurones.

PubMed

Marchand-Pauvert, V; Mazevet, D; Pierrot-Deseilligny, E; Pol, S; Pradat-Diehl, P

1999-04-01

The possibility was investigated that human handedness is associated with an asymmetrical cortical and/or peripheral control of the cervical premotoneurones (PreMNs) that have been shown to mediate part of the descending command to motoneurones of forearm muscles. Heteronymous facilitation evoked in the ongoing voluntary extensor carpi radialis (ECR) electromyographic activity (EMG) by weak (0.8 times motor threshold) stimulation of the musculo-cutaneous (MC) nerve was assessed during tonic co-contraction of biceps and ECR. Suppression evoked by stimulation of a cutaneous nerve (superficial radial, SR) at 4 times perception threshold in both the voluntary EMG and in the motor evoked potential (MEP) elicited in ECR by transcranial magnetic stimulation (TMS) was investigated during isolated ECR contraction. Measurements were performed within time windows or at interstimulus intervals where peripheral and cortical inputs may interact at the level of PreMNs. Results obtained on both sides were compared in consistent right- and left-handers. MC-induced facilitation of the voluntary ECR EMG was significantly larger on the preferred side, whereas there was no asymmetry in the SR-evoked depression of the ongoing ECR EMG. In addition, the suppression of the ECR MEP by the same SR stimulation was more pronounced on the dominant side during unilateral, but not during bilateral, ECR contraction. It is argued that (1) asymmetry in MC-induced facilitation of the voluntary EMG reflects a greater efficiency of the peripheral heteronymous volley in facilitating PreMNs on the dominant side; (2) asymmetry in SR-induced suppression of the MEP during unilateral ECR contraction, which is not paralleled by a similar asymmetry of voluntary EMG suppression, reflects a higher excitability of cortical neurones controlling inhibitory spinal pathways to cervical PreMNs on the preferred side.

Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves.

PubMed

Davis, T S; Wark, H A C; Hutchinson, D T; Warren, D J; O'Neill, K; Scheinblum, T; Clark, G A; Normann, R A; Greger, B

2016-06-01

An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject's phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback.

Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves

NASA Astrophysics Data System (ADS)

Davis, T. S.; Wark, H. A. C.; Hutchinson, D. T.; Warren, D. J.; O'Neill, K.; Scheinblum, T.; Clark, G. A.; Normann, R. A.; Greger, B.

2016-06-01

Objective. An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. Approach. Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject’s phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. Main results. The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. Significance. This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback.

Low-frequency rTMS inhibitory effects in the primary motor cortex: Insights from TMS-evoked potentials.

PubMed

Casula, Elias P; Tarantino, Vincenza; Basso, Demis; Arcara, Giorgio; Marino, Giuliana; Toffolo, Gianna Maria; Rothwell, John C; Bisiacchi, Patrizia S

2014-09-01

The neuromodulatory effects of repetitive transcranial magnetic stimulation (rTMS) have been mostly investigated by peripheral motor-evoked potentials (MEPs). New TMS-compatible EEG systems allow a direct investigation of the stimulation effects through the analysis of TMS-evoked potentials (TEPs). We investigated the effects of 1-Hz rTMS over the primary motor cortex (M1) of 15 healthy volunteers on TEP evoked by single pulse TMS over the same area. A second experiment in which rTMS was delivered over the primary visual cortex (V1) of 15 healthy volunteers was conducted to examine the spatial specificity of the effects. Single-pulse TMS evoked four main components: P30, N45, P60 and N100. M1-rTMS resulted in a significant decrease of MEP amplitude and in a significant increase of P60 and N100 amplitude. There was no effect after V1-rTMS. 1-Hz rTMS appears to increase the amount of inhibition following a TMS pulse, as demonstrated by the higher N100 and P60, which are thought to originate from GABAb-mediated inhibitory post-synaptic potentials. Our results confirm the reliability of the TMS-evoked N100 as a marker of cortical inhibition and provide insight into the neuromodulatory effects of 1-Hz rTMS. The present finding could be of relevance for therapeutic and diagnostic purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

Developing and Evaluating a Flexible Wireless Microcoil Array Based Integrated Interface for Epidural Cortical Stimulation.

PubMed

Wang, Xing; Chaudhry, Sharjeel A; Hou, Wensheng; Jia, Xiaofeng

2017-02-05

Stroke leads to serious long-term disability. Electrical epidural cortical stimulation has made significant improvements in stroke rehabilitation therapy. We developed a preliminary wireless implantable passive interface, which consists of a stimulating surface electrode, receiving coil, and single flexible passive demodulated circuit printed by flexible printed circuit (FPC) technique and output pulse voltage stimulus by inductively coupling an external circuit. The wireless implantable board was implanted in cats' unilateral epidural space for electrical stimulation of the primary visual cortex (V1) while the evoked responses were recorded on the contralateral V1 using a needle electrode. The wireless implantable board output stable monophasic voltage stimuli. The amplitude of the monophasic voltage output could be adjusted by controlling the voltage of the transmitter circuit within a range of 5-20 V. In acute experiment, cortico-cortical evoked potential (CCEP) response was recorded on the contralateral V1. The amplitude of N2 in CCEP was modulated by adjusting the stimulation intensity of the wireless interface. These results demonstrated that a wireless interface based on a microcoil array can offer a valuable tool for researchers to explore electrical stimulation in research and the dura mater-electrode interface can effectively transmit electrical stimulation.

Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat.

PubMed

Hurteau, Marie-France; Thibaudier, Yann; Dambreville, Charline; Danner, Simon M; Rybak, Ilya A; Frigon, Alain

2018-04-25

When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response. SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the contacted limb and opposite homologous limb help maintain balance and forward progression. Here, we investigated reflexes during quadrupedal locomotion in the cat by electrically stimulating cutaneous nerves in each of the four limbs. Functionally, responses appear to modify the trajectory or stabilize the movement of the stimulated limb while modifying the support phase of the other limbs. Reflexes between limbs are mediated by fast-conducting pathways that involve excitatory and inhibitory circuits controlling each limb. The comparatively stronger descending pathways from cervical to lumbar circuits controlling the forelimbs and hindlimbs, respectively, could serve a protective function. Copyright © 2018 the authors 0270-6474/18/384104-19$15.00/0.

Torque and mechanomyogram relationships during electrically-evoked isometric quadriceps contractions in persons with spinal cord injury.

PubMed

Ibitoye, Morufu Olusola; Hamzaid, Nur Azah; Hasnan, Nazirah; Abdul Wahab, Ahmad Khairi; Islam, Md Anamul; Kean, Victor S P; Davis, Glen M

2016-08-01

The interaction between muscle contractions and joint loading produces torques necessary for movements during activities of daily living. However, during neuromuscular electrical stimulation (NMES)-evoked contractions in persons with spinal cord injury (SCI), a simple and reliable proxy of torque at the muscle level has been minimally investigated. Thus, the purpose of this study was to investigate the relationships between muscle mechanomyographic (MMG) characteristics and NMES-evoked isometric quadriceps torques in persons with motor complete SCI. Six SCI participants with lesion levels below C4 [(mean (SD) age, 39.2 (7.9) year; stature, 1.71 (0.05) m; and body mass, 69.3 (12.9) kg)] performed randomly ordered NMES-evoked isometric leg muscle contractions at 30°, 60° and 90° knee flexion angles on an isokinetic dynamometer. MMG signals were detected by an accelerometer-based vibromyographic sensor placed over the belly of rectus femoris muscle. The relationship between MMG root mean square (MMG-RMS) and NMES-evoked torque revealed a very high association (R(2)=0.91 at 30°; R(2)=0.98 at 60°; and R(2)=0.97 at 90° knee angles; P<0.001). MMG peak-to-peak (MMG-PTP) and stimulation intensity were less well related (R(2)=0.63 at 30°; R(2)=0.67 at 60°; and R(2)=0.45 at 90° knee angles), although were still significantly associated (P≤0.006). Test-retest interclass correlation coefficients (ICC) for the dependent variables ranged from 0.82 to 0.97 for NMES-evoked torque, between 0.65 and 0.79 for MMG-RMS, and from 0.67 to 0.73 for MMG-PTP. Their standard error of measurements (SEM) ranged between 10.1% and 31.6% (of mean values) for torque, MMG-RMS and MMG-PTP. The MMG peak frequency (MMG-PF) of 30Hz approximated the stimulation frequency, indicating NMES-evoked motor unit firing rate. The results demonstrated knee angle differences in the MMG-RMS versus NMES-isometric torque relationship, but a similar torque related pattern for MMG-PF. These findings suggested that MMG was well associated with torque production, reliably tracking the motor unit recruitment pattern during NMES-evoked muscle contractions. The strong positive relationship between MMG signal and NMES-evoked torque production suggested that the MMG might be deployed as a direct proxy for muscle torque or fatigue measurement during leg exercise and functional movements in the SCI population. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Auditory steady state responses and cochlear implants: Modeling the artifact-response mixture in the perspective of denoising

PubMed Central

Mina, Faten; Attina, Virginie; Duroc, Yvan; Veuillet, Evelyne; Truy, Eric; Thai-Van, Hung

2017-01-01

Auditory steady state responses (ASSRs) in cochlear implant (CI) patients are contaminated by the spread of a continuous CI electrical stimulation artifact. The aim of this work was to model the electrophysiological mixture of the CI artifact and the corresponding evoked potentials on scalp electrodes in order to evaluate the performance of denoising algorithms in eliminating the CI artifact in a controlled environment. The basis of the proposed computational framework is a neural mass model representing the nodes of the auditory pathways. Six main contributors to auditory evoked potentials from the cochlear level and up to the auditory cortex were taken into consideration. The simulated dynamics were then projected into a 3-layer realistic head model. 32-channel scalp recordings of the CI artifact-response were then generated by solving the electromagnetic forward problem. As an application, the framework’s simulated 32-channel datasets were used to compare the performance of 4 commonly used Independent Component Analysis (ICA) algorithms: infomax, extended infomax, jade and fastICA in eliminating the CI artifact. As expected, two major components were detectable in the simulated datasets, a low frequency component at the modulation frequency and a pulsatile high frequency component related to the stimulation frequency. The first can be attributed to the phase-locked ASSR and the second to the stimulation artifact. Among the ICA algorithms tested, simulations showed that infomax was the most efficient and reliable in denoising the CI artifact-response mixture. Denoising algorithms can induce undesirable deformation of the signal of interest in real CI patient recordings. The proposed framework is a valuable tool for evaluating these algorithms in a controllable environment ahead of experimental or clinical applications. PMID:28350887

Auditory steady state responses and cochlear implants: Modeling the artifact-response mixture in the perspective of denoising.

PubMed

Mina, Faten; Attina, Virginie; Duroc, Yvan; Veuillet, Evelyne; Truy, Eric; Thai-Van, Hung

2017-01-01

Auditory steady state responses (ASSRs) in cochlear implant (CI) patients are contaminated by the spread of a continuous CI electrical stimulation artifact. The aim of this work was to model the electrophysiological mixture of the CI artifact and the corresponding evoked potentials on scalp electrodes in order to evaluate the performance of denoising algorithms in eliminating the CI artifact in a controlled environment. The basis of the proposed computational framework is a neural mass model representing the nodes of the auditory pathways. Six main contributors to auditory evoked potentials from the cochlear level and up to the auditory cortex were taken into consideration. The simulated dynamics were then projected into a 3-layer realistic head model. 32-channel scalp recordings of the CI artifact-response were then generated by solving the electromagnetic forward problem. As an application, the framework's simulated 32-channel datasets were used to compare the performance of 4 commonly used Independent Component Analysis (ICA) algorithms: infomax, extended infomax, jade and fastICA in eliminating the CI artifact. As expected, two major components were detectable in the simulated datasets, a low frequency component at the modulation frequency and a pulsatile high frequency component related to the stimulation frequency. The first can be attributed to the phase-locked ASSR and the second to the stimulation artifact. Among the ICA algorithms tested, simulations showed that infomax was the most efficient and reliable in denoising the CI artifact-response mixture. Denoising algorithms can induce undesirable deformation of the signal of interest in real CI patient recordings. The proposed framework is a valuable tool for evaluating these algorithms in a controllable environment ahead of experimental or clinical applications.

A repetitive intracortical microstimulation pattern induces long-lasting synaptic depression in brain slices of the rat primary somatosensory cortex.

PubMed

Heusler, P; Cebulla, B; Boehmer, G; Dinse, H R

2000-12-01

Repetitive intracortical microstimulation (ICMS) applied to the rat primary somatosensory cortex (SI) in vivo was reported to induce reorganization of receptive fields and cortical maps. The present study was designed to examine the effect of such an ICMS pattern applied to layer IV of brain slices containing SI on the efficacy of synaptic input to layer II/III. Effects of ICMS on the synaptic strength was quantified for the first synaptic component (s1) of cortical field potentials (FPs) recorded from layer II/III of SI. FPs were evoked by stimulation in layer IV. The pattern of ICMS was identical to that used in vivo. However, stimulation intensity had to be raised to induce an alteration of synaptic strength. In brain slices superfused with standard ACSF, repetitive ICMS induced a short-lasting (60 min) reduction of the amplitude (-37%) and the slope (-61%) of s1 evoked from the ICMS site, while the amplitude and the slope of s1 evoked from a control stimulation site in cortical layer IV underwent a slow onset increase (13% and 50%, respectively). In brain slices superfused with ACSF containing 1.25 microM bicuculline, ICMS induced an initial strong reduction of the amplitude (-50%) and the slope (-79%) of s1 evoked from the ICMS site. These effects decayed to a sustained level of depression by -30% (amplitude) and -60% (slope). In contrast to experiments using standard ACSF, s1 evoked from the control site was not affected by ICMS. The presynaptic volley was not affected in either of the two groups of experiments. A conventional high frequency stimulation (HFS) protocol induced input-specific long-term potentiation (LTP) of the amplitude and slope of s1 (25% and 76%, respectively). Low frequency stimulation (LFS) induced input-specific long-term depression (LTD) of the amplitude and slope of s1 (24% and 30%, respectively). Application of common forms of conditioning stimulation (HFS and LFS) resulted in LTP or LTD of s1, indicating normal susceptibility of the brain slices studied to the induction of common forms of synaptic plasticity. Therefore, the effects of repetitive ICMS on synaptic FP components were considered ICMS-specific forms of short-lasting (standard ACSF) or long-lasting synaptic depression (ACSF containing bicuculline), the latter resembling neocortical LTD. Results of this study suggest that synaptic depression of excitatory mechanisms are involved in the cortical reorganization induced by repetitive ICMS in vivo. An additional contribution of an ICMS-induced modification of inhibitory mechanisms to cortical reorganization is discussed.

Intrinsic optical signal imaging of glucose-stimulated physiological responses in the insulin secreting INS-1 β-cell line

NASA Astrophysics Data System (ADS)

Li, Yi-Chao; Cui, Wan-Xing; Wang, Xu-Jing; Amthor, Franklin; Yao, Xin-Cheng

2011-03-01

Intrinsic optical signal (IOS) imaging has been established for noninvasive monitoring of stimulus-evoked physiological responses in the retina and other neural tissues. Recently, we extended the IOS imaging technology for functional evaluation of insulin secreting INS-1 cells. INS-1 cells provide a popular model for investigating β-cell dysfunction and diabetes. Our experiments indicate that IOS imaging allows simultaneous monitoring of glucose-stimulated physiological responses in multiple cells with high spatial (sub-cellular) and temporal (sub-second) resolution. Rapid image sequences reveal transient optical responses that have time courses comparable to glucose-evoked β-cell electrical activities.

Reconsidering Food Reward, Brain Stimulation, and Dopamine: Incentives Act Forward.

PubMed

Newquist, Gunnar; Gardner, R Allen

2015-01-01

In operant conditioning, rats pressing levers and pigeons pecking keys depend on contingent food reinforcement. Food reward agrees with Skinner's behaviorism, undergraduate textbooks, and folk psychology. However, nearly a century of experimental evidence shows, instead, that food in an operant conditioning chamber acts forward to evoke species-specific feeding behavior rather than backward to reinforce experimenter-defined responses. Furthermore, recent findings in neuroscience show consistently that intracranial stimulation to reward centers and dopamine release, the proposed reward molecule, also act forward to evoke inborn species-specific behavior. These results challenge longstanding views of hedonic learning and must be incorporated into contemporary learning theory.

Unpredictable interference of new transcranial motor-evoked potential monitor against the implanted pacemaker.

PubMed

Hayashi, Kazuko

2016-12-01

Recently, NuVasive NV-M5 nerve monitoring system, a new transcranial motor-evoked potential (TcMEP) monitor, has been introduced with the spread of flank-approach spinal operations such as extreme lateral interbody fusion, to prevent nerve damage. Conventional TcMEP monitors use changes in MEP wave patterns, such as amplitude and/or latency, whereas the NV-M5 nerve monitor system first measures the MEP baseline waveform from the transcranial-evoked potential then measures the electric current necessary to obtain the standard of the previous baseline wave pattern at subsequent monitoring times. The NV-M5 monitor determines nerve damage according to the increase in necessary electric current threshold. The NV-M5 monitor also uses a local electrical stimulation mode to monitor the safety of setting screws into the lumbar vertebrae. In this way, various electrical stimulations with various durations and frequencies are used, and electrical noise may result in unpredictable interference with cardiac pacemakers. We performed anesthetic management of extreme lateral interbody fusion surgery using the NV-M5 in a patient with an implanted pacemaker, during which TcMEP stimulation caused interference with the implanted pacemaker. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effect of Contralateral Acoustic Stimulation on Spontaneous Otoacoustic Emissions

PubMed Central

Dhar, Sumitrajit

2009-01-01

Evoked otoacoustic emissions are often used to study the medial olivocochlear (MOC) efferents in humans. There has been concern that the emission-evoking stimulus may itself elicit efferent activity and alter the evoked otoacoustic emission. Spontaneous otoacoustic emissions (SOAEs) are hence advantageous as no external stimulation is necessary to record the response in the test ear. Contralateral acoustic stimulation (CAS) has been shown to suppress SOAE level and elevate SOAE frequency, but the time course of these effects is largely unknown. By utilizing the Choi–Williams distribution, here we report a gradual adaptation during the presence of CAS and an overshoot following CAS offset in both SOAE magnitude and frequency from six normal-hearing female human subjects. Furthermore, we have quantified the time constants of both magnitude and frequency shifts at the onset, presence, and offset of four levels of CAS. Most studies using contralateral elicitors do not stringently control the middle-ear muscle (MEM) reflex, leaving the results difficult to interpret. In addition to clinically available measures of the MEM reflex, we have incorporated a sensitive laboratory technique to monitor the MEM reflex in our subjects, allowing us to interpret the results with greater confidence. PMID:19798532

Frequency-tuning characteristics of cervical and ocular vestibular evoked myogenic potentials induced by air-conducted tone bursts.

PubMed

Park, Hong Ju; Lee, In-Sik; Shin, Jung Eun; Lee, Yeo Jin; Park, Mun Su

2010-01-01

To better characterize both ocular and cervical vestibular evoked myogenic potentials (VEMP) responses at different frequencies of sound in 20 normal subjects. Cervical and ocular VEMPs were recorded. The intensities of sound stimulation decreased from the maximal intensity, until no responses were evoked. Thresholds, amplitudes, latencies and interaural amplitude difference ratio (IADR) at the maximal stimulation were calculated. Both tests showed the similar frequency tuning, with the lowest threshold and highest amplitude for 500-Hz tone-burst stimuli. Sound stimulation at 500Hz showed the response rates of 100% in both tests. Cervical VEMPs showed higher incidence than ocular VEMPs. Ocular VEMP thresholds were significantly higher than those of cervical VEMP. Cervical VEMP amplitudes were significantly higher than ocular VEMP amplitudes. IADRs of ocular and cervical VEMPs did not differ significantly. Ocular VEMP showed the similar frequency tuning to cervical VEMP. Cervical VEMP responses showed higher incidence, lower thresholds and larger amplitudes than ocular VEMP. Cervical VEMP is a more reliable measure than ocular VEMP, though the results of both tests will be complementary. Five hundred Hertz is the optimal frequency to use. Copyright 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Calcium released by photolysis of DM-nitrophen stimulates transmitter release at squid giant synapse.

PubMed

Delaney, K R; Zucker, R S

1990-07-01

1. Transmitter release at the squid giant synapse was stimulated by photolytic release of Ca2+ from the 'caged' Ca2+ compound DM-nitrophen (Kaplan & Ellis-Davies, 1988) inserted into presynaptic terminals. 2. Competing binding reactions cause the amount of Ca2+ released by DM-nitrophen photolysis to depend on the concentrations of DM-nitrophen, total Ca2+, Mg+, ATP and native cytoplasmic Ca2+ buffer. Measurements of presynaptic [Ca2+] changes by co-injection of the fluorescent indicator dye Fura-2 show that DM-nitrophen photolysis causes a transient rise in Ca2+ followed by decay within about 150 ms to an increased steady-state level. 3. Rapid photolysis of Ca2(+)-loaded nitrophen within the presynaptic terminal was followed in less than a millisecond by depolarization of the postsynaptic membrane. As with action potential-evoked excitatory postsynaptic potentials (EPSPs), the light-evoked response was partially and reversibly blocked by 1-3 mM-kainic acid which desensitizes postsynaptic glutamate receptors. 4. Release was similar in magnitude and rate to normal action potential-mediated EPSPs. 5. The release of transmitter by photolysis of Ca2(+)-loaded DM-nitrophen was not affected by removal of Ca2+ from the saline or addition of tetrodotoxin. Photolysis of DM-nitrophen injected into presynaptic terminals without added Ca2+ did not stimulate release of transmitter nor did it interfere with normal action potential-mediated release. 6. Stimulation of presynaptic action potentials in Ca2(+)-free saline during the light-evoked response did not elicit increased release of transmitter if the ganglion was bathed in Ca2(+)-free saline, i.e. in the absence of Ca2+ influx. Increasing the intensity of the light or stimulating presynaptic action potentials in Ca2(+)-containing saline increased the release of transmitter. Therefore the failure of presynaptic voltage change to increase transmitter release resulting from release of caged Ca2+ was not due to saturation or inhibition of the release mechanism by light-released Ca2+. 7. Decreasing the temperature of the preparation increased the delay to onset of the light-evoked response and reduced its amplitude and rate of rise to an extent similar to that observed for action potential-evoked EPSPs.

Different forms of decision-making involve changes in the synaptic strength of the thalamic, hippocampal, and amygdalar afferents to the medial prefrontal cortex.

PubMed

López-Ramos, Juan Carlos; Guerra-Narbona, Rafael; Delgado-García, José M

2015-01-01

Decision-making and other cognitive processes are assumed to take place in the prefrontal cortex. In particular, the medial prefrontal cortex (mPFC) is identified in rodents by its dense connectivity with the mediodorsal (MD) thalamus, and because of its inputs from other sites, such as hippocampus and amygdala (Amyg). The aim of this study was to find a putative relationship between the behavior of mice during the performance of decision-making tasks that involve penalties as a consequence of induced actions, and the strength of field postsynaptic potentials (fPSPs) evoked in the prefrontal cortex from its thalamic, hippocampal, and amygdalar afferents. Mice were chronically implanted with stimulating electrodes in the MD thalamus, the hippocampal CA1 area, or the basolateral amygdala (BLA), and with recording electrodes in the prelimbic/infralimbic area of the prefrontal cortex. Additional stimulating electrodes aimed at evoking negative reinforcements were implanted on the trigeminal nerve. FPSPs evoked at the mPFC from the three selected projecting areas during the food/shock decision-making task decreased in amplitude with shock intensity and animals' avoidance of the reward. FPSPs collected during the operant task also decreased in amplitude (but that evoked by amygdalar stimulation) when lever presses were associated with a trigeminal shock. Results showed a general decrease in the strength of these potentials when animals inhibited their natural or learned appetitive behaviors, suggesting an inhibition of the prefrontal cortex in these conflicting situations.

Different forms of decision-making involve changes in the synaptic strength of the thalamic, hippocampal, and amygdalar afferents to the medial prefrontal cortex

PubMed Central

López-Ramos, Juan Carlos; Guerra-Narbona, Rafael; Delgado-García, José M.

2015-01-01

Decision-making and other cognitive processes are assumed to take place in the prefrontal cortex. In particular, the medial prefrontal cortex (mPFC) is identified in rodents by its dense connectivity with the mediodorsal (MD) thalamus, and because of its inputs from other sites, such as hippocampus and amygdala (Amyg). The aim of this study was to find a putative relationship between the behavior of mice during the performance of decision-making tasks that involve penalties as a consequence of induced actions, and the strength of field postsynaptic potentials (fPSPs) evoked in the prefrontal cortex from its thalamic, hippocampal, and amygdalar afferents. Mice were chronically implanted with stimulating electrodes in the MD thalamus, the hippocampal CA1 area, or the basolateral amygdala (BLA), and with recording electrodes in the prelimbic/infralimbic area of the prefrontal cortex. Additional stimulating electrodes aimed at evoking negative reinforcements were implanted on the trigeminal nerve. FPSPs evoked at the mPFC from the three selected projecting areas during the food/shock decision-making task decreased in amplitude with shock intensity and animals’ avoidance of the reward. FPSPs collected during the operant task also decreased in amplitude (but that evoked by amygdalar stimulation) when lever presses were associated with a trigeminal shock. Results showed a general decrease in the strength of these potentials when animals inhibited their natural or learned appetitive behaviors, suggesting an inhibition of the prefrontal cortex in these conflicting situations. PMID:25688195

Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation.

PubMed

Cash, Robin F H; Murakami, Takenobu; Chen, Robert; Thickbroom, Gary W; Ziemann, Ulf

2016-01-01

Cellular studies showed that disinhibition, evoked pharmacologically or by a suitably timed priming stimulus, can augment long-term plasticity (LTP) induction. We demonstrated previously that transcranial magnetic stimulation evokes a period of presumably GABA(B)ergic late cortical disinhibition (LCD) in human primary motor cortex (M1). Here, we hypothesized that, in keeping with cellular studies, LCD can augment LTP-like plasticity in humans. In Experiment 1, patterned repetitive TMS was applied to left M1, consisting of 6 trains (intertrain interval, 8 s) of 4 doublets (interpulse interval equal to individual peak I-wave facilitation, 1.3-1.5 ms) spaced by the individual peak LCD (interdoublet interval (IDI), 200-250 ms). This intervention (total of 48 pulses applied over ∼45 s) increased motor-evoked potential amplitude, a marker of corticospinal excitability, in a right hand muscle by 147% ± 4%. Control experiments showed that IDIs shorter or longer than LCD did not result in LTP-like plasticity. Experiment 2 indicated topographic specificity to the M1 hand region stimulated by TMS and duration of the LTP-like plasticity of 60 min. In conclusion, GABA(B)ergic LCD offers a powerful new approach for augmenting LTP-like plasticity induction in human cortex. We refer to this protocol as disinhibition stimulation (DIS). © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cutaneous inputs from the back abolish locomotor-like activity and reduce spastic-like activity in the adult cat following complete spinal cord injury

PubMed Central

Frigon, Alain; Thibaudier, Yann; Johnson, Michael D.; Heckman, C.J.; Hurteau, Marie-France

2012-01-01

Spasticity is a condition that can include increased muscle tone, clonus, spasms, and hyperreflexia. In this study, we report the effect of manually stimulating the dorsal lumbosacral skin on spontaneous locomotor-like activity and on a variety of reflex responses in 5 decerebrate chronic spinal cats treated with clonidine. Cats were spinalized 1 month before the terminal experiment. Stretch reflexes were evoked by stretching the left triceps surae muscles. Crossed reflexes were elicited by electrically stimulating the right tibial or superficial peroneal nerves. Windup of reflex responses was evoked by electrically stimulating the left tibial or superficial peroneal nerves. We found that pinching the skin of the back abolished spontaneous locomotor-like activity. We also found that back pinch abolished the rhythmic activity observed during reflex testing without eliminating the reflex responses. Some of the rhythmic episodes of activity observed during reflex testing were consistent with clonus with an oscillation frequency greater than 3 Hz. Pinching the skin of the back effectively abolished rhythmic activity occurring spontaneously or evoked during reflex testing, irrespective of oscillation frequency. The results are consistent with the hypothesis that locomotion and clonus are produced by common central pattern-generators. Stimulating the skin of the back could prove helpful in managing undesired rhythmic activity in spinal cord-injured humans. PMID:22487200

Dynamics of male pelvic floor muscle contraction observed with transperineal ultrasound imaging differ between voluntary and evoked coughs.

PubMed

Stafford, Ryan E; Mazzone, Stuart; Ashton-Miller, James A; Constantinou, Christos; Hodges, Paul W

2014-04-15

Coughing provokes stress urinary incontinence, and voluntary coughs are employed clinically to assess pelvic floor dysfunction. Understanding urethral dynamics during coughing in men is limited, and it is unclear whether voluntary coughs are an appropriate surrogate for spontaneous coughs. We aimed to investigate the dynamics of urethral motion in continent men during voluntary and evoked coughs. Thirteen men (28-42 years) with no history of urological disorders volunteered to participate. Transperineal ultrasound (US) images were recorded and synchronized with measures of intraabdominal pressure (IAP), airflow, and abdominal/chest wall electromyography during voluntary coughs and coughs evoked by inhalation of nebulized capsaicin. Temporal and spatial aspects of urethral movement induced by contraction of the striated urethral sphincter (SUS), levator ani (LA), and bulbocavernosus (BC) muscles and mechanical aspects of cough generation were investigated. Results showed coughing involved complex urethral dynamics. Urethral motion implied SUS and BC shortening and LA lengthening during preparatory and expulsion phases. Evoked coughs resulted in greater IAP, greater bladder base descent (LA lengthening), and greater midurethral displacement (SUS shortening). The preparatory inspiration cough phase was shorter during evoked coughs, as was the latency between onset of midurethral displacement and expulsion. Maximum midurethral displacement coincided with maximal bladder base descent during voluntary cough, but followed it during evoked cough. The data revealed complex interaction between muscles involved in continence in men. Spatial and temporal differences in urethral dynamics and cough mechanics between cough types suggest that voluntary coughing may not adequately assess capacity of the continence mechanism.

Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia.

PubMed

Kingma, J G; Linderoth, B; Ardell, J L; Armour, J A; DeJongste, M J; Foreman, R D

2001-08-13

Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure-volume loops. SCS was accomplished by stimulating the dorsal T1-T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure-volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure-volume dynamics in the anesthetized experimental preparation.

Complexin Mutants Reveal Partial Segregation between Recycling Pathways That Drive Evoked and Spontaneous Neurotransmission

PubMed Central

Sabeva, Nadezhda; Cho, Richard W.; Vasin, Alexander; Gonzalez, Agustin; Littleton, J. Troy

2017-01-01

Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses. We examined synaptic vesicle recycling pathways at complexin null neuromuscular junctions, where spontaneous release is dramatically enhanced. We combined loading of the lipophilic dye FM1–43 with photoconversion, electron microscopy, and electrophysiology to monitor evoked and spontaneous recycling vesicle pools. We found that the total number of recycling vesicles was equal to those retrieved through spontaneous and evoked pools, suggesting that retrieval following fusion is partially segregated for spontaneous and evoked release. In addition, the kinetics of FM1–43 destaining and synaptic depression measured in the presence of the vesicle-refilling blocker bafilomycin indicated that spontaneous and evoked recycling pools partially intermix during the release process. Finally, FM1–43 photoconversion combined with electron microscopy analysis indicated that spontaneous recycling preferentially involves synaptic vesicles in the vicinity of AZs, whereas vesicles recycled following evoked release involve a larger intraterminal pool. Together, these results suggest that spontaneous and evoked vesicles use separable recycling pathways and then partially intermix during subsequent rounds of fusion. SIGNIFICANCE STATEMENT Neurotransmitter release involves fusion of synaptic vesicles with the plasma membrane in response to an action potential, or spontaneously in the absence of stimulation. Upon fusion, vesicles are retrieved and recycled, and it is unclear whether recycling pathways for evoked and spontaneous vesicles are segregated after fusion. We addressed this question by taking advantage of preparations lacking the synaptic protein complexin, which have elevated spontaneous release that enables reliable tracking of the spontaneous recycling pool. Our results suggest that spontaneous and evoked recycling pathways are segregated during the retrieval process but can partially intermix during stimulation. PMID:28077717

Independent component analysis for cochlear implant artifacts attenuation from electrically evoked auditory steady-state response measurements

NASA Astrophysics Data System (ADS)

Deprez, Hanne; Gransier, Robin; Hofmann, Michael; van Wieringen, Astrid; Wouters, Jan; Moonen, Marc

2018-02-01

Objective. Electrically evoked auditory steady-state responses (EASSRs) are potentially useful for objective cochlear implant (CI) fitting and follow-up of the auditory maturation in infants and children with a CI. EASSRs are recorded in the electro-encephalogram (EEG) in response to electrical stimulation with continuous pulse trains, and are distorted by significant CI artifacts related to this electrical stimulation. The aim of this study is to evaluate a CI artifacts attenuation method based on independent component analysis (ICA) for three EASSR datasets. Approach. ICA has often been used to remove CI artifacts from the EEG to record transient auditory responses, such as cortical evoked auditory potentials. Independent components (ICs) corresponding to CI artifacts are then often manually identified. In this study, an ICA based CI artifacts attenuation method was developed and evaluated for EASSR measurements with varying CI artifacts and EASSR characteristics. Artifactual ICs were automatically identified based on their spectrum. Main results. For 40 Hz amplitude modulation (AM) stimulation at comfort level, in high SNR recordings, ICA succeeded in removing CI artifacts from all recording channels, without distorting the EASSR. For lower SNR recordings, with 40 Hz AM stimulation at lower levels, or 90 Hz AM stimulation, ICA either distorted the EASSR or could not remove all CI artifacts in most subjects, except for two of the seven subjects tested with low level 40 Hz AM stimulation. Noise levels were reduced after ICA was applied, and up to 29 ICs were rejected, suggesting poor ICA separation quality. Significance. We hypothesize that ICA is capable of separating CI artifacts and EASSR in case the contralateral hemisphere is EASSR dominated. For small EASSRs or large CI artifact amplitudes, ICA separation quality is insufficient to ensure complete CI artifacts attenuation without EASSR distortion.

Effect of higher frequency on the classification of steady-state visual evoked potentials

NASA Astrophysics Data System (ADS)

Won, Dong-Ok; Hwang, Han-Jeong; Dähne, Sven; Müller, Klaus-Robert; Lee, Seong-Whan

2016-02-01

Objective. Most existing brain-computer interface (BCI) designs based on steady-state visual evoked potentials (SSVEPs) primarily use low frequency visual stimuli (e.g., <20 Hz) to elicit relatively high SSVEP amplitudes. While low frequency stimuli could evoke photosensitivity-based epileptic seizures, high frequency stimuli generally show less visual fatigue and no stimulus-related seizures. The fundamental objective of this study was to investigate the effect of stimulation frequency and duty-cycle on the usability of an SSVEP-based BCI system. Approach. We developed an SSVEP-based BCI speller using multiple LEDs flickering with low frequencies (6-14.9 Hz) with a duty-cycle of 50%, or higher frequencies (26-34.7 Hz) with duty-cycles of 50%, 60%, and 70%. The four different experimental conditions were tested with 26 subjects in order to investigate the impact of stimulation frequency and duty-cycle on performance and visual fatigue, and evaluated with a questionnaire survey. Resting state alpha powers were utilized to interpret our results from the neurophysiological point of view. Main results. The stimulation method employing higher frequencies not only showed less visual fatigue, but it also showed higher and more stable classification performance compared to that employing relatively lower frequencies. Different duty-cycles in the higher frequency stimulation conditions did not significantly affect visual fatigue, but a duty-cycle of 50% was a better choice with respect to performance. The performance of the higher frequency stimulation method was also less susceptible to resting state alpha powers, while that of the lower frequency stimulation method was negatively correlated with alpha powers. Significance. These results suggest that the use of higher frequency visual stimuli is more beneficial for performance improvement and stability as time passes when developing practical SSVEP-based BCI applications.

Effect of higher frequency on the classification of steady-state visual evoked potentials.

PubMed

Won, Dong-Ok; Hwang, Han-Jeong; Dähne, Sven; Müller, Klaus-Robert; Lee, Seong-Whan

2016-02-01

Most existing brain-computer interface (BCI) designs based on steady-state visual evoked potentials (SSVEPs) primarily use low frequency visual stimuli (e.g., <20 Hz) to elicit relatively high SSVEP amplitudes. While low frequency stimuli could evoke photosensitivity-based epileptic seizures, high frequency stimuli generally show less visual fatigue and no stimulus-related seizures. The fundamental objective of this study was to investigate the effect of stimulation frequency and duty-cycle on the usability of an SSVEP-based BCI system. We developed an SSVEP-based BCI speller using multiple LEDs flickering with low frequencies (6-14.9 Hz) with a duty-cycle of 50%, or higher frequencies (26-34.7 Hz) with duty-cycles of 50%, 60%, and 70%. The four different experimental conditions were tested with 26 subjects in order to investigate the impact of stimulation frequency and duty-cycle on performance and visual fatigue, and evaluated with a questionnaire survey. Resting state alpha powers were utilized to interpret our results from the neurophysiological point of view. The stimulation method employing higher frequencies not only showed less visual fatigue, but it also showed higher and more stable classification performance compared to that employing relatively lower frequencies. Different duty-cycles in the higher frequency stimulation conditions did not significantly affect visual fatigue, but a duty-cycle of 50% was a better choice with respect to performance. The performance of the higher frequency stimulation method was also less susceptible to resting state alpha powers, while that of the lower frequency stimulation method was negatively correlated with alpha powers. These results suggest that the use of higher frequency visual stimuli is more beneficial for performance improvement and stability as time passes when developing practical SSVEP-based BCI applications.

Improving the detection of evoked responses to periodic stimulation by using bivariate local spectral F-test - Application to EEG during photic stimulation.

PubMed

Felix, Leonardo Bonato; Rocha, Paulo Fábio; Mendes, Eduardo Mazoni Andrade Marçal; Miranda de Sá, Antonio Mauricio Ferreira Leite

2017-10-01

The spectral local F-test has been applied for detecting evoked responses to rhythmic stimulation that are embedded in the ongoing electroencephalogram (EEG). Based on the sampling distribution of a flat spectrum at the neighbourhood of the stimulation frequency, spectral peaks in an EEG signal that are due to the stimulation may be readily assessed. Nevertheless, the performance of the technique is strongly affected by both the signal-to-noise ratio (SNR) of the responses and the number of data segments used in the estimation. The present work aims at both deriving and evaluating a multivariate extension of local F-test by including the EEG collected at a second distinct derivation. The detection rate with this multivariate detector was found to be greater than that using a single channel in case of equal SNR in both signals. Monte Carlo simulation results showed that the probability of detection with this new detector saturates for signal-to-noise ratios above 12 dB and indicated a greater detection rate in practical situations, even when smaller SNR-values are found in the added signal (e.g. 5 dB for 16 neighbouring frequencies used in the estimation). The technique was next applied to the EEG from 12 subjects during intermittent, photic stimulation leading to superior performance in comparison with the univariate local F-test. Since a higher detection rate with the proposed technique is achieved without the need of increasing the number of data segments, it allows evoked responses to be detected faster, once the same detection rate may be accomplished with less segments. This might be useful in clinical practice. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Differential inhibitory effect on human nociceptive skin senses induced by local stimulation of thin cutaneous fibers.

PubMed

Nilsson, H J; Schouenborg, J

1999-03-01

It is known that stimulation of thin cutaneous nerve fibers can induce long lasting analgesia through both supraspinal and segmental mechanisms, the latter often exhibiting restricted receptive fields. On this basis, we recently developed a new method, termed cutaneous field stimulation (CFS), for localized stimulation of A delta and C fibers in the superficial part of the skin. In the present study, we have evaluated the effects of CFS on non-nociceptive and nociceptive skin senses. We compared the effects of CFS with those of conventional transcutaneous electrical nerve stimulation (TENS), known to preferentially activate coarse myelinated fibers. A battery of sensory tests were made on the right volar forearm of 20 healthy subjects. CFS (16 electrodes, 4 Hz per electrode, 1 ms, up to 0.8 mA) and TENS (100 Hz, 0.2 ms, up to 26 mA) applied either on the right volar forearm (homotopically), or on the lower right leg (heterotopically) were used as conditioning stimulation for 25 min. The tactile threshold was not affected by either homo- or heterotopical CFS or TENS. The mean thresholds for detecting warming or cooling of the skin were increased by 0.4-0.9 degrees C after homo- but not heterotopical CFS and TENS. Regarding nociceptive skin senses, homo- but not heterotopical CFS, markedly reduced CO2-laser evoked A delta- and C fiber mediated heat pain to 75 and 48% of control, respectively, and mechanically evoked pain to 73% of control. Fabric evoked prickle, was not affected by CFS. Neither homo- nor heterotopical TENS induced any marked analgesic effects. It is concluded that different qualities of nociception can be differentially controlled by CFS.

Parvalbumin interneuron mediated feedforward inhibition controls signal output in the deep layers of the perirhinal‐entorhinal cortex

PubMed Central

Willems, Janske G. P.; Wadman, Wytse J.

2018-01-01

Abstract The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link between the neocortex and the hippocampus. However, neocortical activity is transmitted through the PER and LEC to the hippocampus with a low probability, suggesting the involvement of the inhibitory network. This study explored the role of interneuron mediated inhibition, activated by electrical stimulation in the agranular insular cortex (AiP), in the deep layers of the PER and LEC. Activated synaptic input by AiP stimulation rarely evoked action potentials in the PER‐LEC deep layer excitatory principal neurons, most probably because the evoked synaptic response consisted of a small excitatory and large inhibitory conductance. Furthermore, parvalbumin positive (PV) interneurons—a subset of interneurons projecting onto the axo‐somatic region of principal neurons—received synaptic input earlier than principal neurons, suggesting recruitment of feedforward inhibition. This synaptic input in PV interneurons evoked varying trains of action potentials, explaining the fast rising, long lasting synaptic inhibition received by deep layer principal neurons. Altogether, the excitatory input from the AiP onto deep layer principal neurons is overruled by strong feedforward inhibition. PV interneurons, with their fast, extensive stimulus‐evoked firing, are able to deliver this fast evoked inhibition in principal neurons. This indicates an essential role for PV interneurons in the gating mechanism of the PER‐LEC network. PMID:29341361

Selective stimulation of catecholamine release from bovine adrenal chromaffin cells by an ionotropic purinergic receptor sensitive to 2-methylthio ATP.

PubMed

Tomé, Angelo R; Castro, Enrique; Santos, Rosa M; Rosário, Luís M

2007-06-20

2-Methylthioadenosine 5'-triphosphate (2-MeSATP), formerly regarded as a specific P2Y (metabotropic) purinergic receptor agonist, stimulates Ca2+ influx and evokes catecholamine release from adrenal chromaffin cells. These cells express P2Y and P2X (ionotropic) purinoceptors, with the latter providing an important Ca2+ influx pathway. Using single cell calcium imaging techniques, we have determined whether 2-MeSATP might be a specific P2X receptor agonist in bovine chromaffin cells and assessed the relative role of P2X and P2Y receptors on catecholamine secretion from these cells. ATP raised the [Ca2+]i in ~50% of the cells. Removing extracellular Ca2+ suppressed the [Ca2+]i-raising ability of 2-MeSATP, observed in ~40% of the ATP-sensitive cells. This indicates that 2-MeSATP behaves as a specific ionotropic purinoceptor agonist in bovine chromaffin cells. The 2-MeSATP-induced [Ca2+]i-rises were suppressed by PPADS. UTP raised the [Ca2+]i in ~40% of the ATP-sensitive cells, indicating that these expressed Ca2+-mobilizing P2Y receptors. UTP-sensitive receptors may not be the only P2Y receptors present, as suggested by the observation that ~20% of the ATP-sensitive pool did not respond to either 2-MeSATP or UTP. The average sizes of the ATP- and 2-MeSATP-evoked [Ca2+]i responses were identical in UTP-insensitive cells. 2-MeSATP stimulated Ca2+ influx and evoked catecholamine release, whereas UTP elicited Ca2+ release from intracellular stores but did not evoke secretion. 2-MeSATP-induced secretion was strongly inhibited by Cd2+ and suppressed by extracellular Ca2+ or Na+ removal. TTX inhibited 2-MeSATP-evoked secretion by ~20%. 2-MeSATP is a specific P2X purinoceptor agonist and a potent secretagogue in bovine chromaffin cells. Activation of 2-MeSATP-sensitive receptors stimulates Ca2+ influx mainly via voltage-sensitive Ca2+ channels. For the most part, these are activated by the depolarization brought about by Na+ influx across P2X receptor pores.

The Electrically Evoked Auditory Change Complex Evoked by Temporal Gaps Using Cochlear Implants or Auditory Brainstem Implants in Children With Cochlear Nerve Deficiency.

PubMed

He, Shuman; McFayden, Tyler C; Shahsavarani, Bahar S; Teagle, Holly F B; Ewend, Matthew; Henderson, Lillian; Buchman, Craig A

This study aimed to (1) establish the feasibility of measuring the electrically evoked auditory change complex (eACC) in response to temporal gaps in children with cochlear nerve deficiency (CND) who are using cochlear implants (CIs) and/or auditory brainstem implants (ABIs); and (2) explore the association between neural encoding of, and perceptual sensitivity to, temporal gaps in these patients. Study participants included 5 children (S1 to S5) ranging in age from 3.8 to 8.2 years (mean: 6.3 years) at the time of testing. All subjects were unilaterally implanted with a Nucleus 24M ABI due to CND. For each subject, two or more stimulating electrodes of the ABI were tested. S2, S3, and S5 previously received a CI in the contralateral ear. For these 3 subjects, at least two stimulating electrodes of their CIs were also tested. For electrophysiological measures, the stimulus was an 800-msec biphasic pulse train delivered to individual electrodes at the maximum comfortable level (C level). The electrically evoked responses, including the onset response and the eACC, were measured for two stimulation conditions. In the standard condition, the 800-msec pulse train was delivered uninterrupted to individual stimulating electrodes. In the gapped condition, a temporal gap was inserted into the pulse train after 400 msec of stimulation. Gap durations tested in this study ranged from 2 up to 128 msec. The shortest gap that could reliably evoke the eACC was defined as the objective gap detection threshold (GDT). For behavioral GDT measures, the stimulus was a 500-msec biphasic pulse train presented at the C level. The behavioral GDT was measured for individual stimulating electrodes using a one-interval, two-alternative forced-choice procedure. The eACCs to temporal gaps were recorded successfully in all subjects for at least one stimulating electrode using either the ABI or the CI. Objective GDTs showed intersubject variations, as well as variations across stimulating electrodes of the ABI or the CI within each subject. Behavioral GDTs were measured for one ABI electrode in S2 and for multiple ABI and CI electrodes in S5. All other subjects could not complete the task. S5 showed smaller behavioral GDTs for CI electrodes than those measured for ABI electrodes. One CI and two ABI electrodes in S5 showed comparable objective and behavioral GDTs. In contrast, one CI and two ABI electrodes in S5 and one ABI electrode in S2 showed measurable behavioral GDTs but no identifiable eACCs. The eACCs to temporal gaps were recorded in children with CND using either ABIs or CIs. Both objective and behavioral GDTs showed inter- and intrasubject variations. Consistency between results of eACC recordings and psychophysical measures of GDT was observed for some but not all ABI or CI electrodes in these subjects.

[Effects of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation in rats].

PubMed

Li, Ting; Wang, Wei; Kong, De-lei; Su, Jiao; Kang, Jian

2012-04-01

To explore the influence of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation. Male Sprague-Dawley rats were randomly divided into a control group and a chronic intermittent hypoxia group. Transcranial magnetic stimulation was applied in genioglossus motor cortex of the 2 groups. The responses of transcranial magnetic stimulation were recorded and analyzed by single factor analysis of variance. The anterolateral area provided an optimal motor evoked potential response to transcranial magnetic stimulation in the genioglossus motor cortex of the rats. Genioglossus motor evoked potential latency and amplitude were significantly modified by intermittent hypoxic exposure, with a significant decrease in latency (F = 3.294, P < 0.01) at the 1st day [(4.90 ± 0.54) ms] and the 14th day [(4.64 ± 1.71) ms], and an increase in amplitude (F = 1.905, P < 0.05) at the 1st day [(2.28 ± 0.57) mV] and the 7th day [(1.89 ± 0.20) mV]. Intermittent hypoxia could increase the transcranial magnetic stimulation response of genioglossus motor cortex in rats.

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability.

PubMed

Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 ( n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 ( n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability.

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability

PubMed Central

Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability. PMID:28392766

An investigation into the relative merits of pituitary adenylate cyclase-activating polypeptide (PACAP-27) and vasoactive intestinal polypeptide as vagal neuro-transmitters in exocrine pancreas of rats.

PubMed

Wheeler, S; Eardley, J E; McNulty, K F; Sutcliffe, C P; Morrison, J D

1997-07-01

Pancreatic exocrine secretions were collected over 15 min periods and analysed in terms of weight of juice, total HCO3- and total protein in anaesthetized and pithed rats. Pituitary adenylate cyclase-activating polypeptide (PACAP) (i.v.) evoked a serous HCO3- secretion which contained relatively little protein, together with a marked vasodepressor action. The latter was still maximal at lower doses of PACAP, which evoked diminished pancreatic secretions. The effects of PACAP were similar to those evoked by the same dose of VIP and by cervical vagal stimulation, while secretion evoked a much larger secretion of fluid and HCO3-. The time courses of the PACAP-evoked secretions were significantly delayed compared with those of VIP. In the pithed rat, PACAP caused the same level of pancreatic secretions as in the anaesthetized rat, though this was now accompanied by a substantial pressor response which was blocked by phentolamine or prazosin, indicating that it was alpha 1-adrenoceptor mediated. VIP caused a depressor response in the pithed rat, as well as the same level of pancreatic secretions as in the anaesthetized rat. The putative VIP antagonist [Lys1,Pro25,Arg3,4,Tyr6]-VIP (abbreviated as VIPi) caused a selective and significant reduction in the HCO3- secretion evoked by VIP and blocked the vasodepressor response caused by VIP. By contrast, VIPi did not antagonize either the secretory or vasodepressor actions of PACAP. Unilateral electrical stimulation of the cervical vagus nerve evoked significant increases in the weight of juice, total protein and total HCO3- secreted. When preceded by injection of VIPi, vagally evoked secretions were unchanged in terms of weight of juice and total protein but had a significantly reduced HCO3- content. These results are consistent with the release of VIP, though not PACAP, as a vagal neurotransmitter in the exocrine pancreas.

Internalization of the chemokine receptor CCR4 can be evoked by orthosteric and allosteric receptor antagonists

PubMed Central

Ajram, Laura; Begg, Malcolm; Slack, Robert; Cryan, Jenni; Hall, David; Hodgson, Simon; Ford, Alison; Barnes, Ashley; Swieboda, Dawid; Mousnier, Aurelie; Solari, Roberto

2014-01-01

The chemokine receptor CCR4 has at least two natural agonist ligands, MDC (CCL22) and TARC (CCL17) which bind to the same orthosteric site with a similar affinity. Both ligands are known to evoke chemotaxis of CCR4-bearing T cells and also elicit CCR4 receptor internalization. A series of small molecule allosteric antagonists have been described which displace the agonist ligand, and inhibit chemotaxis. The aim of this study was to determine which cellular coupling pathways are involved in internalization, and if antagonists binding to the CCR4 receptor could themselves evoke receptor internalization. CCL22 binding coupled CCR4 efficiently to β-arrestin and stimulated GTPγS binding however CCL17 did not couple to β-arrestin and only partially stimulated GTPγS binding. CCL22 potently induced internalization of almost all cell surface CCR4, while CCL17 showed only weak effects. We describe four small molecule antagonists that were demonstrated to bind to two distinct allosteric sites on the CCR4 receptor, and while both classes inhibited agonist ligand binding and chemotaxis, one of the allosteric sites also evoked receptor internalization. Furthermore, we also characterize an N-terminally truncated version of CCL22 which acts as a competitive antagonist at the orthosteric site, and surprisingly also evokes receptor internalization without demonstrating any agonist activity. Collectively this study demonstrates that orthosteric and allosteric antagonists of the CCR4 receptor are capable of evoking receptor internalization, providing a novel strategy for drug discovery against this class of target. PMID:24534492

Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine

PubMed Central

Andreou, Anna P.; Holland, Philip R.; Akerman, Simon; Summ, Oliver; Fredrick, Joe

2016-01-01

Abstract A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. PMID:27246325

Neural and Hemodynamic Responses Elicited by Forelimb- and Photo-stimulation in Channelrhodopsin-2 Mice: Insights into the Hemodynamic Point Spread Function

PubMed Central

Vazquez, Alberto L.; Fukuda, Mitsuhiro; Crowley, Justin C.; Kim, Seong-Gi

2014-01-01

Hemodynamic responses are commonly used to map brain activity; however, their spatial limits have remained unclear because of the lack of a well-defined and malleable spatial stimulus. To examine the properties of neural activity and hemodynamic responses, multiunit activity, local field potential, cerebral blood volume (CBV)-sensitive optical imaging, and laser Doppler flowmetry were measured from the somatosensory cortex of transgenic mice expressing Channelrhodopsin-2 in cortex Layer 5 pyramidal neurons. The magnitude and extent of neural and hemodynamic responses were modulated using different photo-stimulation parameters and compared with those induced by somatosensory stimulation. Photo-stimulation-evoked spiking activity across cortical layers was similar to forelimb stimulation, although their activity originated in different layers. Hemodynamic responses induced by forelimb- and photo-stimulation were similar in magnitude and shape, although the former were slightly larger in amplitude and wider in extent. Altogether, the neurovascular relationship differed between these 2 stimulation pathways, but photo-stimulation-evoked changes in neural and hemodynamic activities were linearly correlated. Hemodynamic point spread functions were estimated from the photo-stimulation data and its full-width at half-maximum ranged between 103 and 175 µm. Therefore, submillimeter functional structures separated by a few hundred micrometers may be resolved using hemodynamic methods, such as optical imaging and functional magnetic resonance imaging. PMID:23761666

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors.

PubMed

Fortin, Samantha M; Chartoff, Elena H; Roitman, Mitchell F

2016-02-01

Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiCl-mediated suppression of NAc dopamine release.

Influences of High-Level Features, Gaze, and Scene Transitions on the Reliability of BOLD Responses to Natural Movie Stimuli

PubMed Central

Lu, Kun-Han; Hung, Shao-Chin; Wen, Haiguang; Marussich, Lauren; Liu, Zhongming

2016-01-01

Complex, sustained, dynamic, and naturalistic visual stimulation can evoke distributed brain activities that are highly reproducible within and across individuals. However, the precise origins of such reproducible responses remain incompletely understood. Here, we employed concurrent functional magnetic resonance imaging (fMRI) and eye tracking to investigate the experimental and behavioral factors that influence fMRI activity and its intra- and inter-subject reproducibility during repeated movie stimuli. We found that widely distributed and highly reproducible fMRI responses were attributed primarily to the high-level natural content in the movie. In the absence of such natural content, low-level visual features alone in a spatiotemporally scrambled control stimulus evoked significantly reduced degree and extent of reproducible responses, which were mostly confined to the primary visual cortex (V1). We also found that the varying gaze behavior affected the cortical response at the peripheral part of V1 and in the oculomotor network, with minor effects on the response reproducibility over the extrastriate visual areas. Lastly, scene transitions in the movie stimulus due to film editing partly caused the reproducible fMRI responses at widespread cortical areas, especially along the ventral visual pathway. Therefore, the naturalistic nature of a movie stimulus is necessary for driving highly reliable visual activations. In a movie-stimulation paradigm, scene transitions and individuals’ gaze behavior should be taken as potential confounding factors in order to properly interpret cortical activity that supports natural vision. PMID:27564573

Effects of intermittent theta burst stimulation on cerebral blood flow and cerebral vasomotor reactivity.

PubMed

Pichiorri, Floriana; Vicenzini, Edoardo; Gilio, Francesca; Giacomelli, Elena; Frasca, Vittorio; Cambieri, Chiara; Ceccanti, Marco; Di Piero, Vittorio; Inghilleri, Maurizio

2012-08-01

To determine whether intermittent theta burst stimulation influences cerebral hemodynamics, we investigated changes induced by intermittent theta burst stimulation on the middle cerebral artery cerebral blood flow velocity and vasomotor reactivity to carbon dioxide (CO(2)) in healthy participants. The middle cerebral artery flow velocity and vasomotor reactivity were monitored by continuous transcranial Doppler sonography. Changes in cortical excitability were tested by transcranial magnetic stimulation. In 11 healthy participants, before and immediately after delivering intermittent theta burst stimulation, we tested cortical excitability measured by the resting motor threshold and motor evoked potential amplitude over the stimulated hemisphere and vasomotor reactivity to CO(2) bilaterally. The blood flow velocity was monitored in both middle cerebral arteries throughout the experimental session. In a separate session, we tested the effects of sham stimulation under the same experimental conditions. Whereas the resting motor threshold remained unchanged before and after stimulation, motor evoked potential amplitudes increased significantly (P = .04). During and after stimulation, middle cerebral artery blood flow velocities also remained bilaterally unchanged, whereas vasomotor reactivity to CO(2) increased bilaterally (P = .04). The sham stimulation left all variables unchanged. The expected intermittent theta burst stimulation-induced changes in cortical excitability were not accompanied by changes in cerebral blood flow velocities; however, the bilateral increased vasomotor reactivity suggests that intermittent theta burst stimulation influences the cerebral microcirculation, possibly involving subcortical structures. These findings provide useful information on hemodynamic phenomena accompanying intermittent theta burst stimulation, which should be considered in research aimed at developing this noninvasive, low-intensity stimulation technique for safe therapeutic applications.

Toward brain-computer interface based wheelchair control utilizing tactually-evoked event-related potentials

PubMed Central

2014-01-01

Background People with severe disabilities, e.g. due to neurodegenerative disease, depend on technology that allows for accurate wheelchair control. For those who cannot operate a wheelchair with a joystick, brain-computer interfaces (BCI) may offer a valuable option. Technology depending on visual or auditory input may not be feasible as these modalities are dedicated to processing of environmental stimuli (e.g. recognition of obstacles, ambient noise). Herein we thus validated the feasibility of a BCI based on tactually-evoked event-related potentials (ERP) for wheelchair control. Furthermore, we investigated use of a dynamic stopping method to improve speed of the tactile BCI system. Methods Positions of four tactile stimulators represented navigation directions (left thigh: move left; right thigh: move right; abdomen: move forward; lower neck: move backward) and N = 15 participants delivered navigation commands by focusing their attention on the desired tactile stimulus in an oddball-paradigm. Results Participants navigated a virtual wheelchair through a building and eleven participants successfully completed the task of reaching 4 checkpoints in the building. The virtual wheelchair was equipped with simulated shared-control sensors (collision avoidance), yet these sensors were rarely needed. Conclusion We conclude that most participants achieved tactile ERP-BCI control sufficient to reliably operate a wheelchair and dynamic stopping was of high value for tactile ERP classification. Finally, this paper discusses feasibility of tactile ERPs for BCI based wheelchair control. PMID:24428900

Phagostimulants for larvae of the mimosa webworm, Homadaula anisocentra

Treesearch

John W. Peacock; Frank W. Fisk

1970-01-01

The chemical constituents of honey locust, Gleditsia triacanthos L., leaves were investigated as feeding stimulants for larvae of Homodaula anisocentra Meyrick. A water-soluble fraction evoked a significant feeding response. Several sugars and amino acids were present in this extract, but only sucrose and fructose stimulated...

Precision rodent whisker stimulator with integrated servo-locked control and displacement measurement.

PubMed

Walker, Jennifer L; Monjaraz-Fuentes, Fernanda; Pedrow, Christi R; Rector, David M

2011-03-15

We developed a high speed voice coil based whisker stimulator that delivers precise deflections of a single whisker or group of whiskers in a repeatable manner. The device is miniature, quiet, and inexpensive to build. Multiple stimulators fit together for independent stimulation of four or more whiskers. The system can be used with animals under anesthesia as well as awake animals with head-restraint, and does not require trimming the whiskers. The system can deliver 1-2 mm deflections in 2 ms resulting in velocities up to 900 mm/s to attain a wide range of evoked responses. Since auditory artifacts can influence behavioral studies using whisker stimulation, we tested potential effects of auditory noise by recording somatosensory evoked potentials (SEP) with varying auditory click levels, and with/without 80 dBa background white noise. We found that auditory clicks as low as 40 dBa significantly influence the SEP. With background white noise, auditory clicks as low as 50 dBa were still detected in components of the SEP. For behavioral studies where animals must learn to respond to whisker stimulation, these sounds must be minimized. Together, the stimulator and data system can be used for psychometric vigilance tasks, mapping of the barrel cortex and other electrophysiological paradigms. Copyright © 2010 Elsevier B.V. All rights reserved.

Acoustic Events and “Optophonic” Cochlear Responses Induced by Pulsed Near-Infrared LASER

PubMed Central

Maier, Hannes; Richter, Claus-Peter; Kral, Andrej

2012-01-01

Optical stimulation of neural tissue within the cochlea was described as a possible alternative to electrical stimulation. Most optical stimulation was performed with pulsed lasers operating with near-infrared (NIR) light and in thermal confinement. Under these conditions, the coexistence of laser-induced optoacoustic stimulation of the cochlea (“optophony”) has not been analyzed yet. This study demonstrates that pulsed 1850-nm laser light used for neural stimulation also results in sound pressure levels up to 62 dB peak-to-peak equivalent sound pressure level (SPL) in air. The sound field was confined to a small volume along the laser beam. In dry nitrogen, laser-induced acoustic events disappeared. Hydrophone measurements demonstrated pressure waves for laser fibers immersed in water. In hearing rats, laser-evoked signals were recorded from the cochlea without targeting neural tissue. The signals showed a two-domain response differing in amplitude and latency functions, as well as sensitivity to white-noise masking. The first component had characteristics of a cochlear microphonic potential, and the second component was characteristic for a compound action potential. The present data demonstrate that laser-evoked acoustic events can stimulate a hearing cochlea. Whenever optical stimulation is used, care must be taken to distinguish between such “optophony” and the true optoneural response. PMID:21278011

Functional Imaging of Retinal Photoreceptors and Inner Neurons Using Stimulus-Evoked Intrinsic Optical Signals

PubMed Central

Yao, Xin-Cheng; Li, Yi-Chao

2013-01-01

Retinal development is a dynamic process both anatomically and functionally. High-resolution imaging and dynamic monitoring of photoreceptors and inner neurons can provide important information regarding the structure and function of the developing retina. In this chapter, we describe intrinsic optical signal (IOS) imaging as a high spatiotemporal resolution method for functional study of living retinal tissues. IOS imaging is based on near infrared (NIR) light detection of stimulus-evoked transient change of inherent optical characteristics of the cells. With no requirement for exogenous biomarkers, IOS imaging is totally noninvasive for functional mapping of stimulus-evoked spatiotemporal dynamics of the photoreceptors and inner retinal neurons. PMID:22688714

Long-term stability of sensitivity to intracortical microstimulation of somatosensory cortex.

PubMed

Callier, Thierri; Schluter, Erik W; Tabot, Gregg A; Miller, Lee E; Tenore, Francesco V; Bensmaia, Sliman J

2015-10-01

The dexterous manipulation of objects depends heavily on somatosensory signals from the limb. The development of anthropomorphic robotic arms and of algorithms to decode intended movements from neuronal signals has stimulated the need to restore somatosensation for use in upper-limb neuroprostheses. Without touch and proprioception, patients have difficulty controlling prosthetic limbs to a level that justifies the required invasive surgery. Intracortical microstimulation (ICMS) through chronically implanted electrode arrays has the potential to provide rich and intuitive sensory feedback. This approach to sensory restoration requires, however, that the evoked sensations remain stable over time. To investigate the stability of ICMS-evoked sensations, we measured the ability of non-human primates to detect ICMS over experimental sessions that spanned years. We found that the performance of the animals remained highly stable over time, even when they were tested with electrodes that had experienced extensive stimulation. Given the stability of the sensations that it evokes, ICMS may thus be a viable approach for sensory restoration.

Effects of auditory selective attention on chirp evoked auditory steady state responses.

PubMed

Bohr, Andreas; Bernarding, Corinna; Strauss, Daniel J; Corona-Strauss, Farah I

2011-01-01

Auditory steady state responses (ASSRs) are frequently used to assess auditory function. Recently, the interest in effects of attention on ASSRs has increased. In this paper, we investigated for the first time possible effects of attention on AS-SRs evoked by amplitude modulated and frequency modulated chirps paradigms. Different paradigms were designed using chirps with low and high frequency content, and the stimulation was presented in a monaural and dichotic modality. A total of 10 young subjects participated in the study, they were instructed to ignore the stimuli and after a second repetition they had to detect a deviant stimulus. In the time domain analysis, we found enhanced amplitudes for the attended conditions. Furthermore, we noticed higher amplitudes values for the condition using frequency modulated low frequency chirps evoked by a monaural stimulation. The most difference between attended and unattended modality was exhibited at the dichotic case of the amplitude modulated condition using chirps with low frequency content.

Phasic dopamine release drives rapid activation of striatal D2-receptors

PubMed Central

Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

2014-01-01

Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

Cortical Auditory Evoked Potentials to Evaluate Cochlear Implant Candidacy in an Ear With Long-standing Hearing Loss: A Case Report.

PubMed

Patel, Tirth R; Shahin, Antoine J; Bhat, Jyoti; Welling, D Bradley; Moberly, Aaron C

2016-10-01

We describe a novel use of cortical auditory evoked potentials in the preoperative workup to determine ear candidacy for cochlear implantation. A 71-year-old male was evaluated who had a long-deafened right ear, had never worn a hearing aid in that ear, and relied heavily on use of a left-sided hearing aid. Electroencephalographic testing was performed using free field auditory stimulation of each ear independently with pure tones at 1000 and 2000 Hz at approximately 10 dB above pure-tone thresholds for each frequency and for each ear. Mature cortical potentials were identified through auditory stimulation of the long-deafened ear. The patient underwent successful implantation of that ear. He experienced progressively improving aided pure-tone thresholds and binaural speech recognition benefit (AzBio score of 74%). Findings suggest that use of cortical auditory evoked potentials may serve a preoperative role in ear selection prior to cochlear implantation. © The Author(s) 2016.

Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging

PubMed Central

D'Ausilio, A.; Maffongelli, L.; Bartoli, E.; Campanella, M.; Ferrari, E.; Berry, J.; Fadiga, L.

2014-01-01

The activation of listener's motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners’ tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker's ongoing motor plan. PMID:24778384

Long-term stability of sensitivity to intracortical microstimulation of somatosensory cortex

NASA Astrophysics Data System (ADS)

Callier, Thierri; Schluter, Erik W.; Tabot, Gregg A.; Miller, Lee E.; Tenore, Francesco V.; Bensmaia, Sliman J.

2015-10-01

Objective. The dexterous manipulation of objects depends heavily on somatosensory signals from the limb. The development of anthropomorphic robotic arms and of algorithms to decode intended movements from neuronal signals has stimulated the need to restore somatosensation for use in upper-limb neuroprostheses. Without touch and proprioception, patients have difficulty controlling prosthetic limbs to a level that justifies the required invasive surgery. Intracortical microstimulation (ICMS) through chronically implanted electrode arrays has the potential to provide rich and intuitive sensory feedback. This approach to sensory restoration requires, however, that the evoked sensations remain stable over time. Approach. To investigate the stability of ICMS-evoked sensations, we measured the ability of non-human primates to detect ICMS over experimental sessions that spanned years. Main results. We found that the performance of the animals remained highly stable over time, even when they were tested with electrodes that had experienced extensive stimulation. Significance. Given the stability of the sensations that it evokes, ICMS may thus be a viable approach for sensory restoration.

Intracortical microstimulation of human somatosensory cortex.

PubMed

Flesher, Sharlene N; Collinger, Jennifer L; Foldes, Stephen T; Weiss, Jeffrey M; Downey, John E; Tyler-Kabara, Elizabeth C; Bensmaia, Sliman J; Schwartz, Andrew B; Boninger, Michael L; Gaunt, Robert A

2016-10-19

Intracortical microstimulation of the somatosensory cortex offers the potential for creating a sensory neuroprosthesis to restore tactile sensation. Whereas animal studies have suggested that both cutaneous and proprioceptive percepts can be evoked using this approach, the perceptual quality of the stimuli cannot be measured in these experiments. We show that microstimulation within the hand area of the somatosensory cortex of a person with long-term spinal cord injury evokes tactile sensations perceived as originating from locations on the hand and that cortical stimulation sites are organized according to expected somatotopic principles. Many of these percepts exhibit naturalistic characteristics (including feelings of pressure), can be evoked at low stimulation amplitudes, and remain stable for months. Further, modulating the stimulus amplitude grades the perceptual intensity of the stimuli, suggesting that intracortical microstimulation could be used to convey information about the contact location and pressure necessary to perform dexterous hand movements associated with object manipulation. Copyright © 2016, American Association for the Advancement of Science.

A procedure to detect abnormal sensorimotor control in adolescents with idiopathic scoliosis.

PubMed

Pialasse, Jean-Philippe; Mercier, Pierre; Descarreaux, Martin; Simoneau, Martin

2017-09-01

This work identifies, among adolescents with idiopathic scoliosis, those demonstrating impaired sensorimotor control through a classification procedure comparing the amplitude of their vestibular-evoked postural responses. The sensorimotor control of healthy adolescents (n=17) and adolescents with idiopathic scoliosis (n=52) with either mild (Cobb angle≥15° and ≤30°) or severe (Cobb angle >30°) spine deformation was assessed through galvanic vestibular stimulation. A classification procedure sorted out adolescents with idiopathic scoliosis whether the amplitude of their vestibular-evoked postural response was dissimilar or similar to controls. Compared to controls, galvanic vestibular stimulation evoked larger postural response in adolescents with idiopathic scoliosis. Nonetheless, the classification procedure revealed that only 42.5% of all patients showed impaired sensorimotor control. Consequently, identifying patients with sensorimotor control impairment would allow to apply personalized treatments, help clinicians to establish prognosis and hopefully improve the condition of patients with adolescent idiopathic scoliosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrically evoked reticular lamina and basilar membrane vibrations in mice with alpha tectorin C1509G mutation

NASA Astrophysics Data System (ADS)

Ren, Tianying; He, Wenxuan

2015-12-01

Mechanical coupling between the tectorial membrane and the hair bundles of outer hair cells is crucial for stimulating mechanoelectrical transduction channels, which convert sound-induced vibrations into electrical signal, and for transmitting outer hair cell-generated force back to the basilar membrane to boost hearing sensitivity. It has been demonstrated that the detached tectorial membrane in mice with C1509G alpha tectorin mutation caused hearing loss, but enhanced electrically evoked otoacoustic emissions. To understand how the mutated cochlea emits sounds, the reticular lamina and basilar membrane vibrations were measured in the electrically stimulated cochlea in this study. The results showed that the electrically evoked basilar membrane vibration decreased dramatically while the reticular lamina vibration and otoacoustic emissions exhibited no significant change in C1509G mutation mice. This result indicates that a functional cochlear amplifier and a normal basilar membrane vibration are not required for the outer hair cell-generated sound to exit the cochlea.

Interleaved neuromuscular electrical stimulation: Motor unit recruitment overlap.

PubMed

Wiest, Matheus J; Bergquist, Austin J; Schimidt, Helen L; Jones, Kelvin E; Collins, David F

2017-04-01

In this study, we quantified the "overlap" between motor units recruited by single pulses of neuromuscular electrical stimulation (NMES) delivered over the tibialis anterior muscle (mNMES) and the common peroneal nerve (nNMES). We then quantified the torque produced when pulses were alternated between the mNMES and nNMES sites at 40 Hz ("interleaved" NMES; iNMES). Overlap was assessed by comparing torque produced by twitches evoked by mNMES, nNMES, and both delivered together, over a range of stimulus intensities. Trains of iNMES were delivered at the intensity that produced the lowest overlap. Overlap was lowest (5%) when twitches evoked by both mNMES and nNMES produced 10% peak twitch torque. iNMES delivered at this intensity generated 25% of maximal voluntary dorsiflexion torque (11 Nm). Low intensity iNMES leads to low overlap and produces torque that is functionally relevant to evoke dorsiflexion during walking. Muscle Nerve 55: 490-499, 2017. © 2016 Wiley Periodicals, Inc.

Saccular and utricular inputs to sternocleidomastoid motoneurons of decerebrate cats.

PubMed

Kushiro, K; Zakir, M; Ogawa, Y; Sato, H; Uchino, Y

1999-06-01

Connections from the otolithic organs to sternocleidomastoid (SCM) motoneurons were studied in 20 decerebrate cats. The electrical stimulation was selective for the saccular or the utricular nerves. Postsynaptic potentials were recorded from antidromically identified SCM motoneurons; these muscles participate mainly in neck rotation and flexion. Partial transections of the brainstem at the level of the obex were performed to identify the possible pathway from the otolithic organs to the SCM motoneurons. Saccular or utricular nerve stimulation mainly evoked inhibitory postsynaptic potentials (IPSPs) in the ipsilateral SCM motoneurons. Some of the sacculus-induced IPSPs were preceded by small-amplitude excitatory PSPs (EPSPs). The latencies of the PSPs ranged from 1.8 to 3.1 ms after saccular nerve stimulation and from 1.7 to 2.8 ms after utricular nerve stimulation, indicating that most of the ipsilateral connections were disynaptic. In the contralateral SCM motoneurons, saccular nerve stimulation had no or faint effects, whereas utricular nerve stimulation evoked EPSPs in about two-thirds of neurons, and no visible PSPs in about one-third of neurons. The latencies of the EPSPs ranged from 1.5 to 2.0 ms, indicating the disynaptic connection. Thus, the results suggest a difference between the two otolithic innervating patterns of SCM motoneurons. After transection of the medial vestibulospinal tract (MVST), saccular nerve stimulation did not evoke IPSPs at all in ipsilateral SCM motoneurons, but some (11/40) neurons showed small-amplitude EPSPs. Most (24/33) of the utricular-activated IPSPs disappeared after transection, whereas the other 9 neurons still indicated IPSPs. In the contralateral SCM motoneurons, no utricular-activated EPSPs were recorded after transection. These MVST transection results suggest that most of the otolith-SCM pathways are located in the MVST at the obex level. However, the results also suggest the possibility that other otolith-SCM pathways exist at the obex level.

Quantifying the determinants of decremental response in critical ventricular tachycardia substrate.

PubMed

Beheshti, Mohammadali; Nayyar, Sachin; Magtibay, Karl; Massé, Stéphane; Porta-Sanchez, Andreu; Haldar, Shouvik; Bhaskaran, Abhishek; Vigmond, Edward; Nanthakumar, Kumaraswamy

2018-05-28

Decremental response evoked with extrastimulation (DEEP) is a useful tool for determining diastolic return path of ventricular tachycardia (VT). Though a targeted VT ablation is feasible with this approach, determinants of DEEP response have not been studied OBJECTIVES: To elucidate the effects of clinically relevant factors, specifically, the proximity of the stimulation site to the arrhythmogenic scar, stimulation wave direction, number of channels open in the scar, size of the scar and number of extra stimuli on decrement and entropy of DEEP potentials. In a 3-dimensional bi-domain simulation of human ventricular tissue (TNNP cell model), an irregular subendocardial myopathic region was generated. An irregular channel of healthy tissue with five potential entry branches was shaped into the myopathic region. A bipolar electrogram was derived from two electrodes positioned in the centre of the myopathic region. Evoked delays between far-field and local Electrogram (EGM) following an extrastimulus (S1-S2, 500-350 ms) were measured as the stimulation site, channel branches, and inexcitable tissue size were altered. Stimulation adjacent to the inexcitable tissue from the side opposite to the point-of-entry produces longest DEEP delay. The DEEP delay shortens when the stimulation point is farther away from the scar, and it decreases maximally when stimulation is done from a site beside a conduction barrier. Entropy increases with S2 when stimulation site is from farther away. An unprotected channel structure with multiple side-branch openings had shorter DEEP delay compared to a protected channel structure with a paucity of additional side-branch openings and a point-of-entry on the side opposite to the pacing source. Addition of a second shorter extrastimulus did not universally lead to higher DEEP delay CONCLUSIONS: Location and direction of the wavefront in relation to scar entry and size of scar determine the degree of evoked response while the number of extrastimuli has a small additional decremental effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Convergence of flexor reflex and corticospinal inputs on tibialis anterior network in humans.

PubMed

Mackey, Ann S; Uttaro, Denise; McDonough, Maureen P; Krivis, Lisa I; Knikou, Maria

2016-01-01

Integration between descending and ascending inputs at supraspinal and spinal levels is a key characteristic of neural control of movement. In this study, we characterized convergence of the flexor reflex and corticospinal inputs on the tibialis anterior (TA) network in healthy human subjects. Specifically, we characterized the modulation profiles of the spinal TA flexor reflex following subthreshold and suprathreshold transcranial magnetic stimulation (TMS). We also characterized the modulation profiles of the TA motor evoked potentials (MEPs) following medial arch foot stimulation at sensory and above reflex threshold. TA flexor reflexes were evoked following stimulation of the medial arch of the foot with a 30 ms pulse train at innocuous intensities. TA MEPs were evoked following TMS of the leg motor cortex area. TMS at 0.7 and at 1.2 MEP resting threshold increased the TA flexor reflex when TMS was delivered 40-100 ms after foot stimulation, and decreased the TA flexor reflex when TMS was delivered 25-110 ms before foot stimulation. Foot stimulation at sensory and above flexor reflex threshold induced a similar time-dependent modulation in resting TA MEPs, that were facilitated when foot stimulation was delivered 40-100 ms before TMS. The flexor reflex and MEPs recorded from the medial hamstring muscle were modulated in a similar manner to that observed for the TA flexor reflex and MEP. Cutaneomuscular afferents from the distal foot can increase the output of the leg motor cortex area. Descending motor volleys that directly or indirectly depolarize flexor motoneurons increase the output of the spinal FRA interneuronal network. The parallel facilitation of flexor MEPs and flexor reflexes is likely cortical in origin. Afferent mediated facilitation of corticospinal excitability can be utilized to strengthen motor cortex output in neurological disorders. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

In Vivo Magnetic Stimulation of Rat Sciatic Nerve With Centimeter- and Millimeter-Scale Solenoid Coils.

PubMed

Kagan, Zachary B; RamRakhyani, Anil Kumar; Lazzi, Gianluca; Normann, Richard A; Warren, David J

2016-11-01

Previous reports of magnetic stimulation of the peripheral nervous system (PNS) used various coil geometries, all with outer diameters larger than 35 mm, and stimulation energies in the 50 J range to evoke neural excitation. Recent reports of central nervous system (CNS) activation used sub-mm-scale solenoid coils with mJ energy levels. The goal of this study was to translate the lower energy levels from the CNS to the PNS via using smaller coils placed in closer proximity to the neural tissue. Such a performance improvement would advance the state of the art of magnetic stimulation and provide a path towards new neuroprosthetic devices. Primarily, we investigated the range of coil outer diameters from 25 mm down to 5 mm to better understand the dependence of coil diameter on energy required for PNS activation. Nine cm- and mm-scale copper solenoid coils, with various resistances, inductances, inner and outer diameters, and heights were compared by quantizing neuromuscular responses to magnetic stimulation via capacitive discharge excitation of rat sciatic nerves in vivo. Additionally, the effects of stimulus duration and coil position were investigated. As opposed to prior work, this study compares a subset of stimulation parameters in an intact nerve preparation, and shows that magnetic stimulation with coils that abut the nerve is a reliable, effective method of neuromuscular stimulation. Although we observed different energies required for neuromuscular activation depending on the coil and excitation parameters used, for the experimental configuration, devices, and stimulus waveform shapes presented in this manuscript, no systematic dependence of PNS activation on coil diameter was found, even for the mm-scale coils investigated herein. However, there was a clear relationship between discharge circuit capacitance and energy required to evoke a neuromuscular response. Coils approximately 12 mm in outer diameter and larger consistently evoked responses, whereas coils 5 mm in outer diameter did not. Furthermore, we observed meaningful neuromuscular excitation when stimulating with energies as low as 20 J. Although this is an improvement over prior work, it is still orders of magnitude greater than the energy required for conventional electrical stimulation, suggesting that these devices are presently not suitable for use in an application requiring continued pulsed stimulation. Nevertheless, these devices are suitable for basic research and as clinical tools that infrequently stimulate, such as in diagnostic applications.

Spiking irregularity and frequency modulate the behavioral report of single-neuron stimulation.

PubMed

Doron, Guy; von Heimendahl, Moritz; Schlattmann, Peter; Houweling, Arthur R; Brecht, Michael

2014-02-05

The action potential activity of single cortical neurons can evoke measurable sensory effects, but it is not known how spiking parameters and neuronal subtypes affect the evoked sensations. Here, we examined the effects of spike train irregularity, spike frequency, and spike number on the detectability of single-neuron stimulation in rat somatosensory cortex. For regular-spiking, putative excitatory neurons, detectability increased with spike train irregularity and decreasing spike frequencies but was not affected by spike number. Stimulation of single, fast-spiking, putative inhibitory neurons led to a larger sensory effect compared to regular-spiking neurons, and the effect size depended only on spike irregularity. An ideal-observer analysis suggests that, under our experimental conditions, rats were using integration windows of a few hundred milliseconds or more. Our data imply that the behaving animal is sensitive to single neurons' spikes and even to their temporal patterning. Copyright © 2014 Elsevier Inc. All rights reserved.

Event-related potentials to visual, auditory, and bimodal (combined auditory-visual) stimuli.

PubMed

Isoğlu-Alkaç, Ummühan; Kedzior, Karina; Keskindemirci, Gonca; Ermutlu, Numan; Karamursel, Sacit

2007-02-01

The purpose of this study was to investigate the response properties of event related potentials to unimodal and bimodal stimulations. The amplitudes of N1 and P2 were larger during bimodal evoked potentials (BEPs) than auditory evoked potentials (AEPs) in the anterior sites and the amplitudes of P1 were larger during BEPs than VEPs especially at the parieto-occipital locations. Responses to bimodal stimulation had longer latencies than responses to unimodal stimulation. The N1 and P2 components were larger in amplitude and longer in latency during the bimodal paradigm and predominantly occurred at the anterior sites. Therefore, the current bimodal paradigm can be used to investigate the involvement and location of specific neural generators that contribute to higher processing of sensory information. Moreover, this paradigm may be a useful tool to investigate the level of sensory dysfunctions in clinical samples.

Evoking prescribed spike times in stochastic neurons

NASA Astrophysics Data System (ADS)

Doose, Jens; Lindner, Benjamin

2017-09-01

Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

Pericellular Ca2+ recycling potentiates thrombin-evoked Ca2+ signals in human platelets

PubMed Central

Sage, Stewart O; Pugh, Nicholas; Farndale, Richard W; Harper, Alan G S

2013-01-01

We have previously demonstrated that Na+/Ca2+ exchangers (NCXs) potentiate Ca2+ signaling evoked by thapsigargin in human platelets, via their ability to modulate the secretion of autocoids from dense granules. This link was confirmed in platelets stimulated with the physiological agonist, thrombin, and experiments were performed to examine how Ca2+ removal by the NCX modulates platelet dense granule secretion. In cells loaded with the near-membrane indicator FFP-18, thrombin stimulation was observed to elicit an NCX-dependent accumulation of Ca2+ in a pericellular region around the platelets. To test whether this pericellular Ca2+ accumulation might be responsible for the influence of NCXs over platelet function, platelets were exposed to fast Ca2+ chelators or had their glycocalyx removed. Both manipulations of the pericellular Ca2+ rise reduced thrombin-evoked Ca2+ signals and dense granule secretion. Blocking Ca2+-permeable ion channels had a similar effect, suggesting that Ca2+ exported into the pericellular region is able to recycle back into the platelet cytosol. Single cell imaging with extracellular Fluo-4 indicated that thrombin-evoked rises in extracellular [Ca2+] occurred within the boundary described by the cell surface, suggesting their presence within the open canalicular system (OCS). FFP-18 fluorescence was similarly distributed. These data suggest that upon thrombin stimulation, NCX activity creates a rise in [Ca2+] within the pericellular region of the platelet from where it recycles back into the platelet cytosol, acting to both accelerate dense granule secretion and maintain the initial rise in cytosolic [Ca2+]. PMID:24303163

Wavelet analysis can sensitively describe dynamics of ethanol evoked local field potentials of the slug (Limax marginatus) brain.

PubMed

Schütt, Atsuko; Ito, Iori; Rosso, Osvaldo A; Figliola, Alejandra

2003-10-30

Odorants evoke characteristic, but complex, local field potentials (LFPs) in the molluscan brain. Wavelet tools in combination with Fourier analysis can detect and characterize hitherto unknown discrete, slow potentials underlying the conspicuous oscillations. Ethanol was one of the odorants that we have extensively studied (J. Neurosci. Methods, 119 (2002) 89). To detect new features and to elucidate their functions, we tested the wavelet tools on the ethanol-evoked LFP responses of the slug (Limax) procerebrum. Recordings were made in vitro from the neuropile and the cell layer. The present study led to the following findings: (i) Mutual exclusion. Energy concentrated mainly in two ranges, (a) 0.1-0.4 Hz and (b) 1.56-12.5 Hz, and the sum of energy remained constant throughout experiments regardless of the condition. A redistribution of relative energy within this sum seemed to occur in the course of main, possible interactions between the two components excluding each other ('mutual exclusion'). (ii) Transient signal ordering and disordering. Ethanol stimulation alternatingly evoked periods of strongly time evolving oscillation dominated by the energy of 1.56-12.5 Hz (increase of entropy=disordered or complexly ordered state) and those of near-silence were predominated by the energy of 0.1-0.4 Hz (decrease of entropy=ordered state). (iii) About 0.1 Hz slow wave oscillation. It was robust. The dominant energy oscillation and the resulting large entropy fluctuation were negatively correlated to each other, and revealed strong frequency-tuning or synchronization at this frequency. Our findings suggest that discrete slow waves play functionally important roles in the invertebrate brain, as widely known in vertebrate EEG. Wavelet tools allow an easy interpretation of several minutes of frequency variations in a single display and give precise information on stimulus-evoked complex change of the neural system describing the new state 'more ordered' or 'non-ordered or more complexly ordered'.

Mirth and laughter elicited during brain stimulation.

PubMed

Fernández-Baca Vaca, Guadalupe; Lüders, Hans O; Basha, Maysaa Merhi; Miller, Jonathan P

2011-12-01

There are few reports of laughter and/or mirth evoked by electrical stimulation of the brain. In this study, we present a patient with intractable epilepsy in whom mirth and laughter was consistently produced during stimulation of the left inferior frontal gyrus (opercular part) using stereotactically placed depth electrodes. A review of the literature shows that cortical sites that produce mirth when stimulated are located in the dominant hemisphere close to language areas or cortical negative motor areas.

Hyper-excitability of brainstem pathways in cerebral palsy.

PubMed

Smith, Allison Teresa; Gorassini, Monica Ann

2018-06-27

Individuals with cerebral palsy (CP) experience impairments in the control of head and neck movements, suggesting dysfunction in brainstem circuitry. To examine if brainstem circuitry is altered in CP we compared reflexes evoked in the sternocleidomastoid (SCM) muscle by trigeminal nerve stimulation in adults with CP and age/sex-matched controls. Increasing the intensity of trigeminal nerve stimulation produced progressive increases in the long-latency suppression of ongoing SCM EMG in controls. In contrast, participants with CP showed progressively increased facilitation around the same reflex window, suggesting heightened excitability of brainstem pathways. We also examined if there was altered activation of cortico-brainstem pathways in response to pre-natal injury of the brain. Motor-evoked potentials (MEPs) in the SCM that were conditioned by a prior trigeminal afferent stimulation were more facilitated in CP compared to controls, especially in ipsilateral MEPs that are likely mediated by cortico-reticulospinal pathways. In some participants with CP, but not in controls, a combined trigeminal nerve and cortical stimulation near threshold intensities produced large, long-lasting responses in both the SCM and biceps brachii muscles. We propose that the enhanced excitatory responses evoked from trigeminal and cortical inputs in CP are produced by heightened excitability of brainstem circuits, resulting in the augmented activation of reticulospinal pathways. Enhanced activation of reticulospinal pathways in response to early injury of the corticospinal tract may provide a compensated activation of the spinal cord, or alternatively, contribute to impairments in the precise control of head and neck functions.

Kilohertz and Low-Frequency Electrical Stimulation With the Same Pulse Duration Have Similar Efficiency for Inducing Isometric Knee Extension Torque and Discomfort.

PubMed

Medeiros, Flávia Vanessa; Bottaro, Martim; Vieira, Amilton; Lucas, Tiago Pires; Modesto, Karenina Arrais; Bo, Antonio Padilha L; Cipriano, Gerson; Babault, Nicolas; Durigan, João Luiz Quagliotti

2017-06-01

To test the hypotheses that, as compared with pulsed current with the same pulse duration, kilohertz frequency alternating current would not differ in terms of evoked-torque production and perceived discomfort, and as a result, it would show the same current efficiency. A repeated-measures design with 4 stimuli presented in random order was used to test 25 women: (1) 500-microsecond pulse duration, (2) 250-microsecond pulse duration, (3) 500-microsecond pulse duration and low carrier frequency (1 kHz), (4) 250-microsecond pulse duration and high carrier frequency (4 kHz). Isometric peak torque of quadriceps muscle was measured using an isokinetic dynamometer. Discomfort was measured using a visual analog scale. Currents with long pulse durations induced approximately 21% higher evoked torque than short pulse durations. In addition, currents with 500 microseconds delivered greater amounts of charge than stimulation patterns using 250-microsecond pulse durations (P < 0.05). All currents presented similar discomfort. There was no difference on stimulation efficiency with the same pulse duration. Both kilohertz frequency alternating current and pulsed current, with the same pulse duration, have similar efficiency for inducing isometric knee extension torque and discomfort. However, neuromuscular electrical stimulation (NMES) with longer pulse duration induces higher NMES-evoked torque, regardless of the carrier frequency. Pulse duration is an important variable that should receive more attention for an optimal application of NMES in clinical settings.

Simultaneous detection of P300 and steady-state visually evoked potentials for hybrid brain-computer interface.

PubMed

Combaz, Adrien; Van Hulle, Marc M

2015-01-01

We study the feasibility of a hybrid Brain-Computer Interface (BCI) combining simultaneous visual oddball and Steady-State Visually Evoked Potential (SSVEP) paradigms, where both types of stimuli are superimposed on a computer screen. Potentially, such a combination could result in a system being able to operate faster than a purely P300-based BCI and encode more targets than a purely SSVEP-based BCI. We analyse the interactions between the brain responses of the two paradigms, and assess the possibility to detect simultaneously the brain activity evoked by both paradigms, in a series of 3 experiments where EEG data are analysed offline. Despite differences in the shape of the P300 response between pure oddball and hybrid condition, we observe that the classification accuracy of this P300 response is not affected by the SSVEP stimulation. We do not observe either any effect of the oddball stimulation on the power of the SSVEP response in the frequency of stimulation. Finally results from the last experiment show the possibility of detecting both types of brain responses simultaneously and suggest not only the feasibility of such hybrid BCI but also a gain over pure oddball- and pure SSVEP-based BCIs in terms of communication rate.

Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula

PubMed Central

Harte, Steven E.; Ichesco, Eric; Hampson, Johnson P.; Peltier, Scott J.; Schmidt-Wilcke, Tobias; Clauw, Daniel J.; Harris, Richard E.

2016-01-01

Abstract Pain can be elicited through all mammalian sensory pathways yet cross-modal sensory integration, and its relationship to clinical pain, is largely unexplored. Centralized chronic pain conditions such as fibromyalgia are often associated with symptoms of multisensory hypersensitivity. In this study, female patients with fibromyalgia demonstrated cross-modal hypersensitivity to visual and pressure stimuli compared with age- and sex-matched healthy controls. Functional magnetic resonance imaging revealed that insular activity evoked by an aversive level of visual stimulation was associated with the intensity of fibromyalgia pain. Moreover, attenuation of this insular activity by the analgesic pregabalin was accompanied by concomitant reductions in clinical pain. A multivariate classification method using support vector machines (SVM) applied to visual-evoked brain activity distinguished patients with fibromyalgia from healthy controls with 82% accuracy. A separate SVM classification of treatment effects on visual-evoked activity reliably identified when patients were administered pregabalin as compared with placebo. Both SVM analyses identified significant weights within the insular cortex during aversive visual stimulation. These data suggest that abnormal integration of multisensory and pain pathways within the insula may represent a pathophysiological mechanism in some chronic pain conditions and that insular response to aversive visual stimulation may have utility as a marker for analgesic drug development. PMID:27101425

The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex.

PubMed

Di Lazzaro, V; Pilato, F; Dileone, M; Profice, P; Oliviero, A; Mazzone, P; Insola, A; Ranieri, F; Meglio, M; Tonali, P A; Rothwell, J C

2008-08-15

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (TMS). When applied to motor cortex it leads to after-effects on corticospinal and corticocortical excitability that may reflect LTP/LTD-like synaptic effects. An inhibitory form of TBS (continuous, cTBS) suppresses MEPs, and spinal epidural recordings show this is due to suppression of the I1 volley evoked by TMS. Here we investigate whether the excitatory form of TBS (intermittent, iTBS) affects the same I-wave circuitry. We recorded corticospinal volleys evoked by single pulse TMS of the motor cortex before and after iTBS in three conscious patients who had an electrode implanted in the cervical epidural space for the control of pain. As in healthy subjects, iTBS increased MEPs, and this was accompanied by a significant increase in the amplitude of later I-waves, but not the I1 wave. In two of the patients we tested the excitability of the contralateral cortex and found a significant suppression of the late I-waves. The extent of the changes varied between the three patients, as did their age. To investigate whether age might be a significant contributor to the variability we examined the effect of iTBS on MEPs in 18 healthy subjects. iTBS facilitated MEPs evoked by TMS of the conditioned hemisphere and suppressed MEPs evoked by stimulation of the contralateral hemisphere. There was a slight but non-significant decline in MEP facilitation with age, suggesting that interindividual variability was more important than age in explaining our data. In a subgroup of 10 subjects we found that iTBS had no effect on the duration of the ipsilateral silent period suggesting that the reduction in contralateral MEPs was not due to an increase in ongoing transcallosal inhibition. In conclusion, iTBS affects the excitability of excitatory synaptic inputs to pyramidal tract neurones that are recruited by a TMS pulse, both in the stimulated hemisphere and in the contralateral hemisphere. However the circuits affected differ from those influenced by the inhibitory, cTBS, protocol. The implication is that cTBS and iTBS may have different therapeutic targets.

Timing of cortical excitability changes during the reaction time of movements superimposed on tonic motor activity.

PubMed

Schneider, Cyril; Lavoie, Brigitte A; Barbeau, Hugues; Capaday, Charles

2004-12-01

Seated subjects were instructed to react to an auditory cue by simultaneously contracting the tibialis anterior (TA) muscle of each ankle isometrically. Focal transcranial magnetic stimulation of the leg area of the motor cortex (MCx) was used to determine the time course of changes in motor-evoked potential amplitude (MEP) during the reaction time (RT). In one condition the voluntary contraction was superimposed on tonic EMG activity maintained at 10% of maximal voluntary contraction. In the other condition the voluntary contraction was made starting from rest. MEPs in the TA contralateral to the stimulation coil were evoked at various times during the RT in each condition. These were compared to the control MEPs evoked during tonic voluntary activity or with the subject at rest. The RT was measured trial by trial from the EMG activity of the TA ipsilateral to the magnetic stimulus, taking into account the nearly constant time difference between the two sides. The MEPs became far greater than control MEPs during the RT (mean = 332%, SD = 44 %, of control MEPs, P < 0.001) without any measurable change in the background level of EMG activity. The onset of this facilitation occurred on average 12.80 ms (SD = 7.55 ms) before the RT. There was no difference in the onset of facilitation between the two conditions. Because MEPs were facilitated without a change in the background EMG activity, it is concluded that this facilitation is specifically due to an increase of MCx excitability just before voluntary muscle activation. This conclusion is further reinforced by the observation that MEPs evoked by near-threshold anodal stimuli to the MCx were not facilitated during the RT, in contrast to those evoked by near-threshold transcranial magnetic stimulation. However, several observations in the present and previous studies indicate that MEP amplitude may be more sensitive to alpha-motoneuron activity than to motor cortical neuron activity, an idea that has important methodological implications.

Patterned light flash evoked short latency activity in the visual system of visually normal and in amblyopic subjects.

PubMed

Sjöström, A; Abrahamsson, M

1994-04-01

In a previous experimental study on anaesthetized cat it was shown that a short latency (35-40 ms) cortical potential changed polarity due to the presence or absence of a pattern in the flash stimulus. The results suggested one pathway of neuronal activation in the cortex to a pattern that was within the level of resolution and another to patterns that were not. It was implied that a similar difference in impulse transmission to pattern and non-pattern stimuli may be recorded in humans. The present paper describes recordings of the short-latency visual evoked response to varying light flash checkerboard pattern stimuli of high intensity in visually normal and amblyopic children and adults. When stimulating the normal eye a visual evoked response potential with a peak latency between 35 to 40 ms showed a polarity change to patterned compared to non-patterned stimulation. The visual evoked response resolution limit could be correlated to a visual acuity of 0.5 and below. In amblyopic eyes the shift in polarity was recorded at the acuity limit level. The latency of the pattern depending potential was increased in patients with amblyopia compared to normal, but not directly related to amblyopic degree. It is concluded that the short latency, visual evoked response that mainly represents the retino-geniculo-cortical activation may be used to estimate visual resolution below 0.5 in acuity level.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice

PubMed Central

Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

2016-01-01

Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated pools of neurons that may modulate specific cortical areas. PMID:27147975

Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

PubMed

Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

2016-01-01

Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated pools of neurons that may modulate specific cortical areas.

Proximal and distal esophageal sensitivity is decreased in patients with Barrett’s esophagus

PubMed Central

Krarup, Anne L; Olesen, Søren S; Funch-Jensen, Peter; Gregersen, Hans; Drewes, Asbjørn M

2011-01-01

AIM: To investigate sensations to multimodal pain stimulation in the metaplastic and normal parts of the esophagus in patients with Barrett’s esophagus (BE). METHODS: Fifteen patients with BE and 15 age-matched healthy volunteers were subjected to mechanical, thermal and electrical pain stimuli of the esophagus. Both the metaplastic part and the normal part (4 and 14 cm, respectively, above the esophago-gastric junction) were examined. At sensory thresholds the stimulation intensity, referred pain areas, and evoked brain potentials were recorded. RESULTS: Patients were hyposensitive to heat stimulation both in the metaplastic part [median stimulation time to reach the pain detection threshold: 15 (12-34) s vs 14 (6-23) s in controls; F = 4.5, P = 0.04] and the normal part of the esophagus [median 17 (6-32) s vs 13 (8-20) s in controls; F = 6.2, P = 0.02]. Furthermore, patients were hyposensitive in the metaplastic part of the esophagus to mechanical distension [median volume at moderate pain: 50 (20-50) mL vs 33 (13-50) mL in controls; F = 5.7, P = 0.02]. No indication of central nervous system abnormalities was present, as responses were comparable between groups to electrical pain stimuli in the metaplastic part [median current evoking moderate pain: 13 (6-26) mA vs 12 (9-24) mA in controls; F = 0.1, P = 0.7], and in the normal part of the esophagus [median current evoking moderate pain: 9 (6-16) mA, vs 11 (5-11) mA in controls; F = 3.4, P = 0.07]. Furthermore, no differences were seen for the referred pain areas (P-values all > 0.3) or latencies and amplitudes for the evoked brain potentials (P-values all > 0.1). CONCLUSION: Patients with BE are hyposensitive both in the metaplastic and normal part of esophagus likely as a result of abnormalities affecting peripheral nerve pathways. PMID:21274382

Effects of 10 Hz and 20 Hz Transcranial Alternating Current Stimulation on Automatic Motor Control.

PubMed

Cappon, Davide; D'Ostilio, Kevin; Garraux, Gaëtan; Rothwell, John; Bisiacchi, Patrizia

2016-01-01

In a masked prime choice reaction task, presentation of a compatible prime increases the reaction time to the following imperative stimulus if the interval between mask and prime is around 80-250 ms. This is thought to be due to automatic suppression of the motor plan evoked by the prime, which delays reaction to the imperative stimulus. Oscillatory activity in motor networks around the beta frequency range of 20 Hz is important in suppression of movement. Transcranial alternating current at 20 Hz may be able to drive oscillations in the beta range. To investigate whether transcranial alternating current stimulation (tACS) at 20 Hz would increase automatic inhibition in a masked prime task. As a control we used 10 Hz tACS. Stimulation was delivered at alpha (10 Hz) and beta (20 Hz) frequency over the supplementary motor area and the primary motor cortex (simultaneous tACS of SMA-M1), which are part of the BG-cortical motor loop, during the execution of the subliminal masked prime left/right choice reaction task. We measured the effects on reaction times. Corticospinal excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) evoked in the first dorsal interosseous muscle by transcranial magnetic stimulation (TMS) over M1. The 10 and 20-Hz tACS over SMA-M1 had different effects on automatic inhibition. The 20 Hz tACS increased the duration of automatic inhibition whereas it was decreased by 10 Hz tACS. Neurophysiologically, 20 Hz tACS reduced the amplitude of MEPs evoked from M1, whereas there was no change after 10 Hz tACS. Automatic mechanisms of motor inhibition can be modulated by tACS over motor areas of cortex. tACS may be a useful additional tool to investigate the causal links between endogenous brain oscillations and specific cognitive processes. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapid systemic up-regulation of genes after heat-wounding and electrical stimulation

NASA Technical Reports Server (NTRS)

Davies, E.; Vian, A.; Vian, C.; Stankovic, B.

1997-01-01

When one leaf of a tomato plant is electrically-stimulated or heat-wounded, proteinase inhibitor genes are rapidly up-regulated in distant leaves. The identity of the systemic wound signal(s) is not yet known, but major candidates include hormones transmitted via the phloem or the xylem, the electrically-stimulated self-propagating electrical signal in the phloem (the action potential, AP), or the heat-wound-induced surge in hydraulic pressure in the xylem evoking a local change in membrane potential in adjacent living cells (the variation potential, VP). In order to discriminate between these signals we have adopted two approaches. The first approach involves applying stimuli that evoke known signals and determining whether these signals have similar effects on the "model" transcripts for proteinase inhibitors (pin) and calmodulin (cal). Here we show that a heat wound almost invariably evokes a VP, while an electrical stimulation occasionally evokes an AP, and both of these signals induce accumulation of transcripts encoding proteinase inhibitors. The second approach involves identifying the array of genes turned on by heat-wounding. To this end, we have constructed a subtractive library for heat-wounded tissue, isolated over 800 putatively up-regulated clones, and shown that all but two of the fifty that we have analyzed by Northern hybridization are, indeed, up-regulated. Here we show the early kinetics of up-regulation of three of these transcripts in the terminal (4th) leaf in response to heat-wounding the 3rd leaf, about 5 cm away. Even though these transcripts show somewhat different time courses of induction, with one peaking at 30 min, another at 15 min, and another at 5 min after flaming of a distant leaf, they all exhibit a similar pattern, i.e., a transient period of transcript accumulation preceding a period of transcript decrease, followed by a second period of transcript accumulation.

Movement Along the Spine Induced by Transcranial Electrical Stimulation Related Electrode Positioning.

PubMed

Hoebink, Eric A; Journée, Henricus L; de Kleuver, Marinus; Berends, Hanneke; Racz, Ilona; van Hal, Chantal

2016-07-15

A prospective, nonrandomized cohort study. To describe a technique quantifying movement induced by transcranial electrical stimulation (TES) induced movement in relation to the positioning of electrodes during spinal deformity surgery. TES induced movement may cause injuries and delay surgical procedures. When TES movements are evoked, muscles other than those being monitored any adjustments in stimulation protocols and electrode positioning may be expected to minimize movement whereas preserving quality of monitoring. In this study, seismic evoked responses (SER) induced through TES were studied at different electrode positions. Intraoperative TES-motor evoked potentials were carried out in 12 patients undergoing corrective spine surgery. Accelerometer transducers recorded SER in two directions at four different locations of the spine for TES-electrode montage groups Cz-Fz and C3-C4. A paired t test was used to compare the means of SER and the relationship between movement and TES electrode positioning. SERs were strongest in the upper body. All mean SERs values for the Cz-Fz group were up to five times larger when compared with the C3-C4 group. However, there were no differences between the C3-C4 and Cz-Fz groups in the lower body locations. Both electrode montage groups showed a gradual stepwise reduction in all mean SER values along the spine from the cranial to caudal region. For the upper body locations, there were no significant associations between SER and both montages; in contrast, a significant association SER was demonstrated in the lumbar region. At supramaximum levels, movements resulting from multipulse TES are likely caused by relatively strong contractions from muscles in the neck resulting from direct extracranial stimulation. When interchanging electrode montages in individual cases, the movement in the neck may become reduced. At lumbar levels transcranial evoked muscle contractions dominate movement in the surgically exposed areas. 4.

Potentials evoked by chirp-modulated tones: a new technique to evaluate oscillatory activity in the auditory pathway.

PubMed

Artieda, J; Valencia, M; Alegre, M; Olaziregi, O; Urrestarazu, E; Iriarte, J

2004-03-01

Steady-state potentials are oscillatory responses generated by a rhythmic stimulation of a sensory pathway. The frequency of the response, which follows the frequency of stimulation, is maximal at a stimulus rate of 40 Hz for auditory stimuli. The exact cause of these maximal responses is not known, although some authors have suggested that they might be related to the 'working frequency' of the auditory cortex. Testing of the responses to different frequencies of stimulation may be lengthy if a single frequency is studied at a time. Our aim was to develop a fast technique to explore the oscillatory response to auditory stimuli, using a tone modulated in amplitude by a sinusoid whose frequency increases linearly in frequency ('chirp') from 1 to 120 Hz. Time-frequency transforms were used for the analysis of the evoked responses in 10 subjects. Also, we analyzed whether the peaks in these responses were due to increases of amplitude or to phase-locking phenomena, using single-sweep time-frequency transforms and inter-trial phase analysis. The pattern observed in the time-frequency transform of the chirp-evoked potential was very similar in all subjects: a diagonal band of energy was observed, corresponding to the frequency of modulation at each time instant. Two components were present in the band, one around 45 Hz (30-60 Hz) and a smaller one between 80 and 120 Hz. Inter-trial phase analysis showed that these components were mainly due to phase locking phenomena. A simultaneous testing of the amplitude-modulation-following oscillatory responses to auditory stimulation is feasible using a tone modulated in amplitude at increasing frequencies. The maximal energies found at stimulation frequencies around 40 Hz are probably due to increased phase-locking of the individual responses.

Cortico-cortical and motor evoked potentials to single and paired-pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study.

PubMed

Boulogne, Sébastien; Andre-Obadia, Nathalie; Kimiskidis, Vasilios K; Ryvlin, Philippe; Rheims, Sylvain

2016-11-01

Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Asymmetry of magnetic motor evoked potentials recorded in calf muscles of the dominant and non-dominant lower extremity.

PubMed

Olex-Zarychta, Dorota; Koprowski, Robert; Sobota, Grzegorz; Wróbel, Zygmunt

2009-08-07

The aim of the study was to determine the applicability of magnetic stimulation and magnetic motor evoked potentials (MEPs) in motor asymmetry studies by obtaining quantitative and qualitative measures of efferent activity during low intensity magnetic stimulation of the dominant and non-dominant lower extremities. Magnetic stimulation of the tibial nerve in the popliteal fossa was performed in 10 healthy male right-handed and right-footed young adults. Responses were recorded from the lateral head of the gastrocnemius muscles of the right and left lower extremities. Response characteristics (duration, onset latency, amplitude) were analyzed in relation to the functional dominance of the limbs and in relation to the direction of the current in the magnetic coil by use of the Wilcoxon pair sequence test. The CCW direction of coil current was related to reduced amplitudes of recorded MEPs. Greater amplitudes of evoked potentials were recorded in the non-dominant extremity, both in the CW and CCW coil current directions, with the statistical significance of this effect (p=0.005). No differences in duration of response were found in the CW current direction, while in CCW the time of the left-side response was prolonged (p=0.01). In the non-dominant extremity longer onset latencies were recorded in both current directions, but only for the CW direction the side asymmetries showed a statistical significance of p=0.005. In the dominant extremity the stimulation correlated with stronger paresthesias, especially using the CCW direction of coil current. The results indicate that low intensity magnetic stimulation may be useful in quantitative and qualitative research into the motor asymmetry.

Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face

PubMed Central

Pilurzi, G; Hasan, A; Saifee, T A; Tolu, E; Rothwell, J C; Deriu, F

2013-01-01

Previous studies of the cortical control of human facial muscles documented the distribution of corticobulbar projections and the presence of intracortical inhibitory and facilitatory mechanisms. Yet surprisingly, given the importance and precision in control of facial expression, there have been no studies of the afferent modulation of corticobulbar excitability or of the plasticity of synaptic connections in the facial primary motor cortex (face M1). In 25 healthy volunteers, we used standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods to probe motor-evoked potentials (MEPs), short-intracortical inhibition, intracortical facilitation, short-afferent and long-afferent inhibition and paired associative stimulation in relaxed and active depressor anguli oris muscles. Single-pulse TMS evoked bilateral MEPs at rest and during activity that were larger in contralateral muscles, confirming that corticobulbar projection to lower facial muscles is bilateral and asymmetric, with contralateral predominance. Both short-intracortical inhibition and intracortical facilitation were present bilaterally in resting and active conditions. Electrical stimulation of the facial nerve paired with a TMS pulse 5–200 ms later showed no short-afferent inhibition, but long-afferent inhibition was present. Paired associative stimulation tested with an electrical stimulation–TMS interval of 20 ms significantly facilitated MEPs for up to 30 min. The long-term potentiation, evoked for the first time in face M1, demonstrates that excitability of the facial motor cortex is prone to plastic changes after paired associative stimulation. Evaluation of intracortical circuits in both relaxed and active lower facial muscles as well as of plasticity in the facial motor cortex may provide further physiological insight into pathologies affecting the facial motor system. PMID:23297305

Transcranial Motor-Evoked Potentials Are More Readily Acquired Than Somatosensory-Evoked Potentials in Children Younger Than 6 Years.

PubMed

McIntyre, Ian W; Francis, Lisa; McAuliffe, John J

2016-01-01

There is a general belief that somatosensory-evoked potentials (SSEPs) are more easily obtained than transcranial motor-evoked potentials (TcMEPs) in children younger than 6 years. We tested this assumption and the assumption that motor-evoked potentials are rarely obtained in children younger than 2 years. The records of all patients who were monitored during surgical procedures between April 1, 2010, and June 30, 2013, were reviewed and those who were younger than 72 months at the time of surgery were identified and analyzed for the rate of obtaining clinically useful SSEPs and motor-evoked potentials. Subgroup analysis was performed by age. A total of 146 patients were identified, 9 had SSEPs without TcMEPs monitored, 117 had both TcMEPs and SSEPs monitored, and the remainder had only electromyographic monitoring. All patients who were to have TcMEPs recorded received a total IV anesthetic. Among the 117 patients who had both SSEPs and TcMEPs monitored, clinically relevant TcMEPs were obtained more frequently than SSEPs (110/117 vs 89/117; χ = 14.82; P = 0.00012). There were significant differences between the rates of obtaining SSEPs and TcMEPs in the 0- to 23-month (P = 0.0038) and 24- to 47-month (P = 0.0056) age groups. Utilization of a double-train stimulation technique facilitated obtaining TcMEPs in the youngest patients. TcMEPs can be obtained more easily than SSEPs in patients younger than 72 months if a permissive anesthetic technique is used. The success rate for obtaining TcMEPs can be further enhanced by the use of a temporal facilitation (double-train) stimulation technique.

Notched-noise embedded frequency specific chirps for objective audiometry using auditory brainstem responses

PubMed Central

Corona-Strauss, Farah I.; Schick, Bernhard; Delb, Wolfgang; Strauss, Daniel J.

2012-01-01

It has been shown recently that chirp-evoked auditory brainstem responses (ABRs) show better performance than click stimulations, especially at low intensity levels. In this paper we present the development, test, and evaluation of a series of notched-noise embedded frequency specific chirps. ABRs were collected in healthy young control subjects using the developed stimuli. Results of the analysis of the corresponding ABRs using a time-scale phase synchronization stability (PSS) measure are also reported. The resultant wave V amplitude and latency measures showed a similar behavior as for values reported in literature. The PSS of frequency specific chirp-evoked ABRs reflected the presence of the wave V for all stimulation intensities. The scales that resulted in higher PSS are in line with previous findings, where ABRs evoked by broadband chirps were analyzed, and which stated that low frequency channels are better for the recognition and analysis of chirp-evoked ABRs. We conclude that the development and test of the series of notched-noise embedded frequency specific chirps allowed the assessment of frequency specific ABRs, showing an identifiable wave V for different intensity levels. Future work may include the development of a faster automatic recognition scheme for these frequency specific ABRs. PMID:26557336

Intraoperative Subcortical Fiber Mapping with Subcortico-Cortical Evoked Potentials.

PubMed

Enatsu, Rei; Kanno, Aya; Ohtaki, Shunya; Akiyama, Yukinori; Ochi, Satoko; Mikuni, Nobuhiro

2016-02-01

During brain surgery, there are difficulties associated with identifying subcortical fibers with no clear landmarks. We evaluated the usefulness of cortical evoked potentials with subcortical stimuli (subcortico-cortical evoked potential [SCEP]) in identifying subcortical fibers intraoperatively. We used SCEP to identify the pyramidal tract in 4 patients, arcuate fasciculus in 1 patient, and both in 2 patients during surgical procedures. After resection, a 1 × 4-electrode plate was placed on the floor of the removal cavity and 1-Hz alternating electrical stimuli were delivered to this electrode. A 4 × 5 recording electrode plate was placed on the central cortical areas to map the pyramidal tract and temporoparietal cortical areas for the arcuate fasciculus. SCEPs were obtained by averaging electrocorticograms time locked to the stimulus onset. The subcortical stimulation within 15 mm of the target fiber induced cortical evoked potentials in the corresponding areas, whereas the stimulation apart from 20 mm did not. Five patients showed transient worsening of neurologic symptoms after surgery. However, all patients recovered. SCEP was useful for identifying subcortical fibers and confirmed the preservation of these fibers. This technique is expected to contribute to the effectiveness and safety of resective surgery in patients with lesions close to eloquent areas. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine.

PubMed

Andreou, Anna P; Holland, Philip R; Akerman, Simon; Summ, Oliver; Fredrick, Joe; Goadsby, Peter J

2016-07-01

A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Evoked EMG-based torque prediction under muscle fatigue in implanted neural stimulation

NASA Astrophysics Data System (ADS)

Hayashibe, Mitsuhiro; Zhang, Qin; Guiraud, David; Fattal, Charles

2011-10-01

In patients with complete spinal cord injury, fatigue occurs rapidly and there is no proprioceptive feedback regarding the current muscle condition. Therefore, it is essential to monitor the muscle state and assess the expected muscle response to improve the current FES system toward adaptive force/torque control in the presence of muscle fatigue. Our team implanted neural and epimysial electrodes in a complete paraplegic patient in 1999. We carried out a case study, in the specific case of implanted stimulation, in order to verify the corresponding torque prediction based on stimulus evoked EMG (eEMG) when muscle fatigue is occurring during electrical stimulation. Indeed, in implanted stimulation, the relationship between stimulation parameters and output torques is more stable than external stimulation in which the electrode location strongly affects the quality of the recruitment. Thus, the assumption that changes in the stimulation-torque relationship would be mainly due to muscle fatigue can be made reasonably. The eEMG was proved to be correlated to the generated torque during the continuous stimulation while the frequency of eEMG also decreased during fatigue. The median frequency showed a similar variation trend to the mean absolute value of eEMG. Torque prediction during fatigue-inducing tests was performed based on eEMG in model cross-validation where the model was identified using recruitment test data. The torque prediction, apart from the potentiation period, showed acceptable tracking performances that would enable us to perform adaptive closed-loop control through implanted neural stimulation in the future.

Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles—a TMS Study

PubMed Central

Sale, Martin V.; Rogasch, Nigel C.; Nordstrom, Michael A.

2016-01-01

The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs. PMID:27014031

Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease

PubMed Central

Milosevic, Luka; Kalia, Suneil K; Hodaie, Mojgan; Lozano, Andres M; Fasano, Alfonso; Popovic, Milos R; Hutchison, William D

2018-01-01

Abstract Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical. The objectives of this study were to (i) compare the frequency-dependent effects on cell firing in subthalamic nucleus and substantia nigra pars reticulata; (ii) quantify frequency-dependent effects on short-term plasticity in substantia nigra pars reticulata; and (iii) investigate effects of continuous long-train high frequency stimulation (comparable to conventional deep brain stimulation) on synaptic plasticity. Two closely spaced (600 µm) microelectrodes were advanced into the subthalamic nucleus (n = 27) and substantia nigra pars reticulata (n = 14) of 22 patients undergoing deep brain stimulation surgery for Parkinson’s disease. Cell firing and evoked field potentials were recorded with one microelectrode during stimulation trains from the adjacent microelectrode across a range of frequencies (1–100 Hz, 100 µA, 0.3 ms, 50–60 pulses). Subthalamic firing attenuated with ≥20 Hz (P < 0.01) stimulation (silenced at 100 Hz), while substantia nigra pars reticulata decreased with ≥3 Hz (P < 0.05) (silenced at 50 Hz). Substantia nigra pars reticulata also exhibited a more prominent increase in transient silent period following stimulation. Patients with longer silent periods after 100 Hz stimulation in the subthalamic nucleus tended to have better clinical outcome after deep brain stimulation. At ≥30 Hz the first evoked field potential of the stimulation train in substantia nigra pars reticulata was potentiated (P < 0.05); however, the average amplitude of the subsequent potentials was rapidly attenuated (P < 0.01). This is suggestive of synaptic facilitation followed by rapid depression. Paired pulse ratios calculated at the beginning of the train revealed that 20 Hz (P < 0.05) was the minimum frequency required to induce synaptic depression. Lastly, the average amplitude of evoked field potentials during 1 Hz pulses showed significant inhibitory synaptic potentiation after long-train high frequency stimulation (P < 0.001) and these increases were coupled with increased durations of neuronal inhibition (P < 0.01). The subthalamic nucleus exhibited a higher frequency threshold for stimulation-induced inhibition than the substantia nigra pars reticulata likely due to differing ratios of GABA:glutamate terminals on the soma and/or the nature of their GABAergic inputs (pallidal versus striatal). We suggest that enhancement of inhibitory synaptic plasticity, and frequency-dependent potentiation and depression are putative mechanisms of deep brain stimulation. Furthermore, we foresee that future closed-loop deep brain stimulation systems (with more frequent off stimulation periods) may benefit from inhibitory synaptic potentiation that occurs after high frequency stimulation. PMID:29236966

Stimulation of the cochlea using green laser light

NASA Astrophysics Data System (ADS)

Wenzel, G. I.; Balster, S.; Lim, H. H.; Zhang, K.; Reich, U.; Lubatschowski, H.; Ertmer, W.; Lenarz, T.; Reuter, G.

2009-02-01

The success of conventional hearing aids and electrical cochlear implants have generally been limited to hearing in quiet situations, in part due to a lack of localized (i.e., frequency specificity) sensorineural activation and subsequent impaired speech discrimination in noise. Laser light is a source of energy that can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. Compound action potentials have been elicited using 2.12 µm laser pulses through activation of auditory nerve fibers (Izzo et al. 2006). Laser stimulation (813 nm) of the cochlea has shown to induce basilar membrane motion and cochlear microphonic potentials (Fridberger et al. 2006). We sought to assess if visible light (green, 532 nm, 10 ns pulses) could be used to consistently activate the cochlea. The laser parameters were selected based on our initial attempt to induce an optoacoustic effect as the energy transfer mechanism to the cochlea. Click evoked auditory brainstem responses (AABRs) were recorded preoperatively in ketamine-anesthetized guinea pigs to confirm normal hearing. The bulla and then the cochlea were exposed. Optically evoked ABRs (OABR) were recorded in response to laser stimulation with a 50 µm optical fiber (532 nm, 10 ns pulses, 500 repetitions, 10 pulses/s; Nd:YAG laser) at the round window (RW) directed towards the basilar membrane (BM). OABRs similar in morphology to acoustically evoked ABRs, except for shorter latencies, were obtained for stimulation through the RW with energy levels between 1.7-30 µJ/pulse. The OABRs increased with increasing energy level reaching a saturation level around 13-15 µJ/pulse. Furthermore the responses remained consistent across stimulation over time, including stimulation at 13 µJ/pulse for over 30 minutes, indicating minimal or no damage within the cochlea with this type of laser stimulation. Overall we have demonstrated that laser light stimulation with 532 nm has potential for a new type of auditory prosthesis that can activate the cochlea without any apparent functional damage. Further studies are needed to determine the optimal laser parameters and fiber placement locations for localized and tonotopic activation.

Laser-induced thermoelastic effects can evoke tactile sensations

NASA Astrophysics Data System (ADS)

Jun, Jae-Hoon; Park, Jong-Rak; Kim, Sung-Phil; Min Bae, Young; Park, Jang-Yeon; Kim, Hyung-Sik; Choi, Seungmoon; Jung, Sung Jun; Hwa Park, Seung; Yeom, Dong-Il; Jung, Gu-In; Kim, Ji-Sun; Chung, Soon-Cheol

2015-06-01

Humans process a plethora of sensory information that is provided by various entities in the surrounding environment. Among the five major senses, technology for touch, haptics, is relatively young and has relatively limited applications largely due to its need for physical contact. In this article, we suggest a new way for non-contact haptic stimulation that uses laser, which has potential advantages such as mid-air stimulation, high spatial precision, and long working distance. We demonstrate such tactile stimulation can be enabled by laser-induced thermoelastic effects by means of physical and perceptual studies, as well as simulations. In the physical study, the mechanical effect of laser on a human skin sample is detected using low-power radiation in accordance with safety guidelines. Limited increases (< ~2.5 °C) in temperature at the surface of the skin, examined by both thermal camera and the Monte Carlo simulation, indicate that laser does not evoke heat-induced nociceptive sensation. In the human EEG study, brain responses to both mechanical and laser stimulation are consistent, along with subjective reports of the non-nociceptive sensation of laser stimuli.

Laser-induced thermoelastic effects can evoke tactile sensations.

PubMed

Jun, Jae-Hoon; Park, Jong-Rak; Kim, Sung-Phil; Min Bae, Young; Park, Jang-Yeon; Kim, Hyung-Sik; Choi, Seungmoon; Jung, Sung Jun; Hwa Park, Seung; Yeom, Dong-Il; Jung, Gu-In; Kim, Ji-Sun; Chung, Soon-Cheol

2015-06-05

Humans process a plethora of sensory information that is provided by various entities in the surrounding environment. Among the five major senses, technology for touch, haptics, is relatively young and has relatively limited applications largely due to its need for physical contact. In this article, we suggest a new way for non-contact haptic stimulation that uses laser, which has potential advantages such as mid-air stimulation, high spatial precision, and long working distance. We demonstrate such tactile stimulation can be enabled by laser-induced thermoelastic effects by means of physical and perceptual studies, as well as simulations. In the physical study, the mechanical effect of laser on a human skin sample is detected using low-power radiation in accordance with safety guidelines. Limited increases (< ~2.5 °C) in temperature at the surface of the skin, examined by both thermal camera and the Monte Carlo simulation, indicate that laser does not evoke heat-induced nociceptive sensation. In the human EEG study, brain responses to both mechanical and laser stimulation are consistent, along with subjective reports of the non-nociceptive sensation of laser stimuli.

Corticospinal excitability is dependent on the parameters of peripheral electric stimulation: a preliminary study.

PubMed

Chipchase, Lucy S; Schabrun, Siobhan M; Hodges, Paul W

2011-09-01

To evaluate the effect of 6 electric stimulation paradigms on corticospinal excitability. Using a same subject pre-post test design, transcranial magnetic stimulation (TMS) was used to measure the responsiveness of corticomotor pathway to biceps and triceps brachii muscles before and after 30 minutes of electric stimulation over the biceps brachii. Six different electric stimulation paradigms were applied in random order, at least 3 days apart. Motor control research laboratory. Healthy subjects (N=10; 5 women, 5 men; mean age ± SD, 26 ± 3.6y). Six different electric stimulation paradigms with varied stimulus amplitude, frequency, and ramp settings. Amplitudes of TMS-induced motor evoked potentials at biceps and triceps brachii normalized to maximal M-wave amplitudes. Electric stimulation delivered at stimulus amplitude sufficient to evoke a sensory response at both 10 Hz and 100 Hz, and stimulus amplitude to create a noxious response at 10 Hz decreased corticomotor responsiveness (all P<0.01). Stimulation sufficient to induce a motor contraction (30 Hz) applied in a ramped pattern to mimic a voluntary activation increased corticomotor responsiveness (P=0.002), whereas constant low- and high-intensity motor stimulation at 10 Hz did not. Corticomotor excitability changes were similar for both the stimulated muscle and its antagonist. Stimulus amplitude (intensity) and the nature (muscle flicker vs contraction) of motor stimulation have a significant impact on changes in corticospinal excitability induced by electric stimulation. Here, we demonstrate that peripheral electric stimulation at stimulus amplitude to create a sensory response reduces corticomotor responsiveness. Conversely, stimulus amplitude to create a motor response increases corticomotor responsiveness, but only the parameters that create a motor response that mimics a voluntary muscle contraction. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Pressure generation during neural stimulation with infrared radiation

NASA Astrophysics Data System (ADS)

Xia, N.; Tan, X.; Xu, Y.; Richter, C.-P.

2017-02-01

This study quantifies laser evoked pressure waves in small confined volumes such as a small dish or the cochlea. The pressure was measured with custom fabricated pressure probes in front of the optical fiber. For the pressure measurements during laser stimulation the probes were inserted into scala tympani or vestibuli. At 164 μJ/pulse, the intracochlear pressure was between 96 and 106 dB (re 20 μPa). The pressure was also measured in the ear canal with a sensitive microphone. It was on average 63 dB (re 20 μPa). At radiant energies large enough to evoke an auditory compound action potential, the outer ear canal equivalent pressure was 36-56 dB (re 20 μPa).

Neurophysiological Changes Measured Using Somatosensory Evoked Potentials.

PubMed

Macerollo, Antonella; Brown, Matt J N; Kilner, James M; Chen, Robert

2018-05-01

Measurements of somatosensory evoked potentials (SEPs), recorded using electroencephalography during different phases of movement, have been fundamental in understanding the neurophysiological changes related to motor control. SEP recordings have also been used to investigate adaptive plasticity changes in somatosensory processing related to active and observational motor learning tasks. Combining noninvasive brain stimulation with SEP recordings and intracranial SEP depth recordings, including recordings from deep brain stimulation electrodes, has been critical in identifying neural areas involved in specific temporal stages of somatosensory processing. Consequently, this fundamental information has furthered our understanding of the maladaptive plasticity changes related to pathophysiology of diseases characterized by abnormal movements, such as Parkinson's disease, dystonia, and functional movement disorders. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Vaginal eroticism: a replication study.

PubMed

Alzate, H

1985-12-01

Vaginal eroticism was investigated in a group of 27 coitally experienced volunteers by means of systematic digital stimulation of both vaginal walls. Erogenous zones were found in all subjects, mainly located on the upper anterior wall and the lower posterior one. An orgasmic response was elicited by stimulation of these zones in 89% of the subjects. This study supports previous findings regarding vaginal eroticism. It does not support the existence of the discrete anatomical structure called the Grafenberg spot. It supports the contention that there are two distinct types of female orgasm, vaginally evoked and clitorally evoked. It also supports the finding that some women expel a fluid through the urethra at the time of orgasm. In this particular case the fluid was chemically indistinguishable from urine.

Carbachol inhibits basal and forskolin-evoked adult rat striatal acetylcholine release.

PubMed

Login, I S

1997-05-27

Acutely dissociated adult rat striatal cholinergic neurons labeled with [3H]choline were used in a perifusion system to study muscarinic regulation of basal and forskolin-stimulated fractional [3H]acetylcholine ([3H]-ACh) efflux in the absence of synaptic modulation. Carbachol inhibited basal (40% maximal inhibition; IC50 approximately 0.7 microM) and forskolin-evoked release (75% inhibition; IC50 approximately 0.05 microM) in a concentration-dependent manner, and both carbachol actions were abolished with atropine. Thus, activation of striatal muscarinic cholinergic autoreceptors potently inhibits basal and adenylate cyclase-stimulated ACh release. Tonic inhibitory control of cholinergic activity by functional striatal circuitry apparently prevents detection of these important physiological interactions in slices or in situ.

Peripheral nerve recruitment curve using near-infrared stimulation

NASA Astrophysics Data System (ADS)

Dautrebande, Marie; Doguet, Pascal; Gorza, Simon-Pierre; Delbeke, Jean; Nonclercq, Antoine

2018-02-01

In the context of near-infrared neurostimulation, we report on an experimental hybrid electrode allowing for simultaneous photonic or electrical neurostimulation and for electrical recording of evoked action potentials. The electrode includes three contacts and one optrode. The optrode is an opening in the cuff through which the tip of an optical fibre is held close to the epineurium. Two contacts provide action potential recording. The remaining contact, together with a remote subcutaneous electrode, is used for electric stimulation which allows periodical assessment of the viability of the nerve during the experiment. A 1470 nm light source was used to stimulate a mouse sciatic nerve. Neural action potentials were not successfully recorded because of the electrical noise so muscular activity was used to reflect the motor fibres stimulation. A recruitment curve was obtained by stimulating with photonic pulses of same power and increasing duration and recording the evoked muscular action potentials. Motor fibres can be recruited with radiant exposures between 0.05 and 0.23 J/cm2 for pulses in the 100 to 500 μs range. Successful stimulation at short duration and at a commercial wavelength is encouraging in the prospect of miniaturisation and practical applications. Motor fibres recruitment curve is a first step in an ongoing research work. Neural action potential acquisition will be improved, with aim to shed light on the mechanism of action potential initiation under photonic stimulation.

Novel Stimulation Paradigms with Temporally-Varying Parameters to Reduce Synchronous Activity at the Onset of High Frequency Stimulation in Rat Hippocampus

PubMed Central

Cai, Ziyan; Feng, Zhouyan; Guo, Zheshan; Zhou, Wenjie; Wang, Zhaoxiang; Wei, Xuefeng

2017-01-01

Deep brain stimulation (DBS) has shown wide applications for treating various disorders in the central nervous system by using high frequency stimulation (HFS) sequences of electrical pulses. However, upon the onset of HFS sequences, the narrow pulses could induce synchronous firing of action potentials among large populations of neurons and cause a transient phase of “onset response” that is different from the subsequent steady state. To investigate the transient onset phase, the antidromically-evoked population spikes (APS) were used as an electrophysiological marker to evaluate the synchronous neuronal reactions to axonal HFS in the hippocampal CA1 region of anesthetized rats. New stimulation paradigms with time-varying intensity and frequency were developed to suppress the “onset responses”. Results show that HFS paradigms with ramp-up intensity at the onset phase could suppress large APS potentials. In addition, an intensity ramp with a slower ramp-up rate or with a higher pulse frequency had greater suppression on APS amplitudes. Therefore, to reach a desired pulse intensity rapidly, a stimulation paradigm combining elevated frequency and ramp-up intensity was used to shorten the transition phase of initial HFS without evoking large APS potentials. The results of the study provide important clues for certain transient side effects of DBS and for development of new adaptive stimulation paradigms. PMID:29066946

A model of metastable dynamics during ongoing and evoked cortical activity

NASA Astrophysics Data System (ADS)

La Camera, Giancarlo

The dynamics of simultaneously recorded spike trains in alert animals often evolve through temporal sequences of metastable states. Little is known about the network mechanisms responsible for the genesis of such sequences, or their potential role in neural coding. In the gustatory cortex of alert rates, state sequences can be observed also in the absence of overt sensory stimulation, and thus form the basis of the so-called `ongoing activity'. This activity is characterized by a partial degree of coordination among neurons, sharp transitions among states, and multi-stability of single neurons' firing rates. A recurrent spiking network model with clustered topology can account for both the spontaneous generation of state sequences and the (network-generated) multi-stability. In the model, each network state results from the activation of specific neural clusters with potentiated intra-cluster connections. A mean field solution of the model shows a large number of stable states, each characterized by a subset of simultaneously active clusters. The firing rate in each cluster during ongoing activity depends on the number of active clusters, so that the same neuron can have different firing rates depending on the state of the network. Because of dense intra-cluster connectivity and recurrent inhibition, in finite networks the stable states lose stability due to finite size effects. Simulations of the dynamics show that the model ensemble activity continuously hops among the different states, reproducing the ongoing dynamics observed in the data. Moreover, when probed with external stimuli, the model correctly predicts the quenching of single neuron multi-stability into bi-stability, the reduction of dimensionality of the population activity, the reduction of trial-to-trial variability, and a potential role for metastable states in the anticipation of expected events. Altogether, these results provide a unified mechanistic model of ongoing and evoked cortical dynamics. NSF IIS-1161852, NIDCD K25-DC013557, NIDCD R01-DC010389.

Anodal Transcranial Direct Current Stimulation Shows Minimal, Measure-Specific Effects on Dynamic Postural Control in Young and Older Adults: A Double Blind, Sham-Controlled Study

PubMed Central

Doumas, Michail

2017-01-01

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. PMID:28099522

Anodal Transcranial Direct Current Stimulation Shows Minimal, Measure-Specific Effects on Dynamic Postural Control in Young and Older Adults: A Double Blind, Sham-Controlled Study.

PubMed

Craig, Chesney E; Doumas, Michail

2017-01-01

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.

The nucleus raphe magnus OFF-cells are involved in diffuse noxious inhibitory controls.

PubMed

Chebbi, R; Boyer, N; Monconduit, L; Artola, A; Luccarini, P; Dallel, R

2014-06-01

Diffuse noxious inhibitory controls (DNIC) are very powerful long-lasting descending inhibitory controls which are pivotal in modulating the activity of spinal and trigeminal nociceptive neurons. DNIC are subserved by a loop involving supraspinal structures such as the lateral parabrachial nucleus and the subnucleus reticularis dorsalis. Surprisingly, though, whether the nucleus raphe magnus (NRM), another supraspinal area which is long known to be important in pain modulation, is involved in DNIC is still a matter of discussion. Here, we reassessed the role of the NRM neurons in DNIC by electrophysiologically recording from wide dynamic range (WDR) neurons in the trigeminal subnucleus oralis and pharmacologically manipulating the NRM OFF- and ON-cells. In control conditions, C-fiber-evoked responses in trigeminal WDR neurons are inhibited by a conditioning noxious heat stimulation applied to the hindpaw. We show that inactivating the NRM by microinjecting the GABAA receptor agonist, muscimol, both facilitates C-fiber-evoked responses of trigeminal WDR neurons and strongly attenuates their inhibition by heat applied to the hindpaw. Interestingly, selective blockade of ON-cells by microinjecting the broad-spectrum excitatory amino acid antagonist, kynurenate, into the NRM neither affects C-fiber-evoked responses nor attenuates DNIC of trigeminal WDR neurons. These results indicate that the NRM tonically inhibits trigeminal nociceptive inputs and is involved in the neuronal network underlying DNIC. Moreover, within NRM, OFF-cells might be more specifically involved in both the tonic and phasic descending inhibitory controls of trigeminal nociception. Copyright © 2014 Elsevier Inc. All rights reserved.

The Second Spiking Threshold: Dynamics of Laminar Network Spiking in the Visual Cortex

PubMed Central

Forsberg, Lars E.; Bonde, Lars H.; Harvey, Michael A.; Roland, Per E.

2016-01-01

Most neurons have a threshold separating the silent non-spiking state and the state of producing temporal sequences of spikes. But neurons in vivo also have a second threshold, found recently in granular layer neurons of the primary visual cortex, separating spontaneous ongoing spiking from visually evoked spiking driven by sharp transients. Here we examine whether this second threshold exists outside the granular layer and examine details of transitions between spiking states in ferrets exposed to moving objects. We found the second threshold, separating spiking states evoked by stationary and moving visual stimuli from the spontaneous ongoing spiking state, in all layers and zones of areas 17 and 18 indicating that the second threshold is a property of the network. Spontaneous and evoked spiking, thus can easily be distinguished. In addition, the trajectories of spontaneous ongoing states were slow, frequently changing direction. In single trials, sharp as well as smooth and slow transients transform the trajectories to be outward directed, fast and crossing the threshold to become evoked. Although the speeds of the evolution of the evoked states differ, the same domain of the state space is explored indicating uniformity of the evoked states. All evoked states return to the spontaneous evoked spiking state as in a typical mono-stable dynamical system. In single trials, neither the original spiking rates, nor the temporal evolution in state space could distinguish simple visual scenes. PMID:27582693

Guiding the study of brain dynamics by using first-person data: Synchrony patterns correlate with ongoing conscious states during a simple visual task

PubMed Central

Lutz, Antoine; Lachaux, Jean-Philippe; Martinerie, Jacques; Varela, Francisco J.

2002-01-01

Even during well-calibrated cognitive tasks, successive brain responses to repeated identical stimulations are highly variable. The source of this variability is believed to reside mainly in fluctuations of the subject's cognitive “context” defined by his/her attentive state, spontaneous thought process, strategy to carry out the task, and so on … As these factors are hard to manipulate precisely, they are usually not controlled, and the variability is discarded by averaging techniques. We combined first-person data and the analysis of neural processes to reduce such noise. We presented the subjects with a three-dimensional illusion and recorded their electrical brain activity and their own report about their cognitive context. Trials were clustered according to these first-person data, and separate dynamical analyses were conducted for each cluster. We found that (i) characteristic patterns of endogenous synchrony appeared in frontal electrodes before stimulation. These patterns depended on the degree of preparation and the immediacy of perception as verbally reported. (ii) These patterns were stable for several recordings. (iii) Preparatory states modulate both the behavioral performance and the evoked and induced synchronous patterns that follow. (iv) These results indicated that first-person data can be used to detect and interpret neural processes. PMID:11805299

Striatal somatotopy and motor responses evoked by acute electrical stimulation of the posterior striatum in rats.

PubMed

Vilela-Filho, Osvaldo; Barros, Breno A; Arruda, Mariana M; Castro, Thaisa S; Souza, Joaquim T; Silva, Delson J; Ferraz, Fernando P; Ragazzo, Paulo C

2014-02-01

Previous experiments suggest that the striatal sensorimotor territory in rats is located in its dorsolateral region, along the rostrocaudal axis, unlike what has been observed in primates. In the present study, electrical stimulation was performed to investigate the degree of participation of the posterior striatum in its motor territory, its somatotopic organization, and the motor responses evoked by stimulation. Twenty-five rats were submitted to stereotactic stimulation of the posterior striatum under general anesthesia, receiving consecutively four different current intensities. The motor responses observed in the different body parts were registered for later comparison. We considered as threshold the smallest of these current intensities able to evoke a motor response. The observed motor responses were qualitatively different for each segment: forepaws: ipsilateral, adduction, and contralateral abduction; hindpaws: ipsilateral, flexion, and contralateral, extension/abduction; trunk, rotation/flexion; and tail, rotation/elevation. High-frequency, small-amplitude distal tremor occurred in the ipsilateral forepaw in 95% of the animals. Progressively larger current intensities were necessary for the induction of motor response in the forepaws, hindpaws, and trunk/tail, in that order. The results allowed us to infer the following posterior striatal somatotopic organization: forepaws, posterolaterally, being the contralateral medial to the ipsilateral; trunk/tail, anteromedially; and hindpaws, in an intermediate position, being the contralateral posterior to the ipsilateral. It is suggested that the tremor and the other observed motor responses derive from the excitation of striatal projection neurons and that the striatum may play an important role in the genesis of essential tremor. © 2013 International Neuromodulation Society.

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

PubMed

Kita, Hitoshi; Kita, Takako

2011-07-13

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Central inhibition of initiation of swallowing by systemic administration of diazepam and baclofen in anaesthetized rats.

PubMed

Tsujimura, Takanori; Sakai, Shogo; Suzuki, Taku; Ujihara, Izumi; Tsuji, Kojun; Magara, Jin; Canning, Brendan J; Inoue, Makoto

2017-05-01

Dysphagia is caused not only by neurological and/or structural damage but also by medication. We hypothesized memantine, dextromethorphan, diazepam, and baclofen, all commonly used drugs with central sites of action, may regulate swallowing function. Swallows were evoked by upper airway (UA)/pharyngeal distension, punctate mechanical stimulation using a von Frey filament, capsaicin or distilled water (DW) applied topically to the vocal folds, and electrical stimulation of a superior laryngeal nerve (SLN) in anesthetized rats and were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles and by visualizing laryngeal elevation. The effects of intraperitoneal or topical administration of each drug on swallowing function were studied. Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topically applied diazepam or baclofen had no effect on swallowing. These data indicate that diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. NEW & NOTEWORTHY Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topical applied diazepam or baclofen was without effect on swallowing. Diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. Copyright © 2017 the American Physiological Society.

Tuning Shifts of the Auditory System By Corticocortical and Corticofugal Projections and Conditioning

PubMed Central

Suga, Nobuo

2011-01-01

The central auditory system consists of the lemniscal and nonlemniscal systems. The thalamic lemniscal and non-lemniscal auditory nuclei are different from each other in response properties and neural connectivities. The cortical auditory areas receiving the projections from these thalamic nuclei interact with each other through corticocortical projections and project down to the subcortical auditory nuclei. This corticofugal (descending) system forms multiple feedback loops with the ascending system. The corticocortical and corticofugal projections modulate auditory signal processing and play an essential role in the plasticity of the auditory system. Focal electric stimulation -- comparable to repetitive tonal stimulation -- of the lemniscal system evokes three major types of changes in the physiological properties, such as the tuning to specific values of acoustic parameters of cortical and subcortical auditory neurons through different combinations of facilitation and inhibition. For such changes, a neuromodulator, acetylcholine, plays an essential role. Electric stimulation of the nonlemniscal system evokes changes in the lemniscal system that is different from those evoked by the lemniscal stimulation. Auditory signals ascending from the lemniscal and nonlemniscal thalamic nuclei to the cortical auditory areas appear to be selected or adjusted by a “differential” gating mechanism. Conditioning for associative learning and pseudo-conditioning for nonassociative learning respectively elicit tone-specific and nonspecific plastic changes. The lemniscal, corticofugal and cholinergic systems are involved in eliciting the former, but not the latter. The current article reviews the recent progress in the research of corticocortical and corticofugal modulations of the auditory system and its plasticity elicited by conditioning and pseudo-conditioning. PMID:22155273

Perifornical hypothalamic pathway to the adrenal gland: Role for glutamatergic transmission in the glucose counter-regulatory response.

PubMed

Sabetghadam, A; Korim, W S; Verberne, A J M

2017-03-01

Adrenaline is an important counter-regulatory hormone that helps restore glucose homeostasis during hypoglycaemia. However, the neurocircuitry that connects the brain glucose sensors and the adrenal sympathetic outflow to the chromaffin cells is poorly understood. We used electrical microstimulation of the perifornical hypothalamus (PeH) and the rostral ventrolateral medulla (RVLM) combined with adrenal sympathetic nerve activity (ASNA) recording to examine the relationship between the RVLM, the PeH and ASNA. In urethane-anaesthetised male Sprague-Dawley rats, intermittent single pulse electrical stimulation of the rostroventrolateral medulla (RVLM) elicited an evoked ASNA response that consisted of early (60±3ms) and late peaks (135±4ms) of preganglionic and postganglionic activity. In contrast, RVLM stimulation evoked responses in lumbar sympathetic nerve activity that were almost entirely postganglionic. PeH stimulation also produced an evoked excitatory response consisting of both preganglionic and postganglionic excitatory peaks in ASNA. Both peaks in ASNA following RVLM stimulation were reduced by intrathecal kynurenic acid (KYN) injection. In addition, the ASNA response to systemic neuroglucoprivation induced by 2-deoxy-d-glucose was abolished by bilateral microinjection of KYN into the RVLM. This suggests that a glutamatergic pathway from the perifornical hypothalamus (PeH) relays in the RVLM to activate the adrenal SPN and so modulate ASNA. The main findings of this study are that (i) adrenal premotor neurons in the RVLM may be, at least in part, glutamatergic and (ii) that the input to these neurons that is activated during neuroglucoprivation is also glutamatergic. Copyright © 2017 Elsevier B.V. All rights reserved.

Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells.

PubMed

Chan, S A; Smith, C

2001-12-15

1. Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. 2. The sAPs evoked inward Na(+) and Ca(2+) currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (tau = 560 ms). 3. Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. 4. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. 5. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506.

Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells

PubMed Central

Chan, Shyue-An; Smith, Corey

2001-01-01

Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. The sAPs evoked inward Na+ and Ca2+ currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (τ = 560 ms). Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506. PMID:11744761

Test-retest reliability of evoked heat stimulation BOLD fMRI.

PubMed

Upadhyay, Jaymin; Lemme, Jordan; Anderson, Julie; Bleakman, David; Large, Thomas; Evelhoch, Jeffrey L; Hargreaves, Richard; Borsook, David; Becerra, Lino

2015-09-30

To date, the blood oxygenated-level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique has enabled an objective and deeper understanding of pain processing mechanisms embedded within the human central nervous system (CNS). In order to further comprehend the benefits and limitations of BOLD fMRI in the context of pain as well as the corresponding subjective pain ratings, we evaluated the univariate response, test-retest reliability and confidence intervals (CIs) at the 95% level of both data types collected during evoked stimulation of 40°C (non-noxious), 44°C (mildly noxious) and a subject-specific temperature eliciting a 7/10 pain rating. The test-retest reliability between two scanning sessions was determined by calculating group-level interclass correlation coefficients (ICCs) and at the single-subject level. Across the three stimuli, we initially observed a graded response of increasing magnitude for both VAS (visual analog score) pain ratings and fMRI data. Test-retest reliability was observed to be highest for VAS pain ratings obtained during the 7/10 pain stimulation (ICC=0.938), while ICC values of pain fMRI data for a distribution of CNS structures ranged from 0.5 to 0.859 (p<0.05). Importantly, the upper and lower confidence interval CI bounds reported herein could be utilized in subsequent trials involving healthy volunteers to hypothesize the magnitude of effect required to overcome inherent variability of either VAS pain ratings or BOLD responses evoked during innocuous or noxious thermal stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Mental Load and Fatigue on Steady-State Evoked Potential Based Brain Computer Interface Tasks: A Comparison of Periodic Flickering and Motion-Reversal Based Visual Attention.

PubMed

Xie, Jun; Xu, Guanghua; Wang, Jing; Li, Min; Han, Chengcheng; Jia, Yaguang

Steady-state visual evoked potentials (SSVEP) based paradigm is a conventional BCI method with the advantages of high information transfer rate, high tolerance to artifacts and the robust performance across users. But the occurrence of mental load and fatigue when users stare at flickering stimuli is a critical problem in implementation of SSVEP-based BCIs. Based on electroencephalography (EEG) power indices α, θ, θ + α, ratio index θ/α and response properties of amplitude and SNR, this study quantitatively evaluated the mental load and fatigue in both of conventional flickering and the novel motion-reversal visual attention tasks. Results over nine subjects revealed significant mental load alleviation in motion-reversal task rather than flickering task. The interaction between factors of "stimulation type" and "fatigue level" also illustrated the motion-reversal stimulation as a superior anti-fatigue solution for long-term BCI operation. Taken together, our work provided an objective method favorable for the design of more practically applicable steady-state evoked potential based BCIs.

Reduction of the pace polarization artefact for capture detection applications by a tri-phasic stimulation pulse.

PubMed

Sutton, R; Fröhlig, G; de Voogt, W G; Goethals, M; Hintringer, F; Kennergren, C; Scanu, P; Guilleman, D; Treese, N; Hartung, W M; Stammwitz, E; Muetstege, A

2004-11-01

This study investigated the ability to minimize pace polarization artefacts (PPA) by adjusting the post-stimulus pulse duration of a tri-phasic stimulation pulse. Adjustment of the stimulation pulse was enabled by downloading special study software into an already implanted pacemaker. Tests were performed in a total of 296 atrial leads and 311 ventricular leads. Both chronic and acute leads were included in the study. Statistically significant differences were found in the initial PPA (without any adjustment of the stimulus pulse) between atrial and ventricular leads. In addition, significant differences were observed among various lead models with respect to changes over time in the initial ventricular PPA. Successful PPA reduction was defined as a reduction of the PPA below 0.5 mV for atrial leads and below 1 mV for ventricular leads. Results show a success rate for ventricular and atrial PPA reduction of 97.8% and 98.7%, respectively. Threshold tests showed that after reduction of the PPA loss of ventricular capture can be reliably detected. However, atrial threshold tests showed many false positive evoked response detections. In addition, unexpectedly high evoked response amplitudes were observed in the atrium after reduction of the PPA. Results from additional measurements suggest that these high atrial evoked response amplitudes come from the influence of the input filter of the pacemaker.

Cortical Inhibition in Attention Deficit Hyperactivity Disorder: New Insights from the Electroencephalographic Response to Transcranial Magnetic Stimulation

ERIC Educational Resources Information Center

Bruckmann, Sarah; Hauk, Daniela; Roessner, Veit; Resch, Franz; Freitag, Christine M.; Kammer, Thomas; Ziemann, Ulf; Rothenberger, Aribert; Weisbrod, Matthias; Bender, Stephan

2012-01-01

Attention deficit hyperactivity disorder is one of the most frequent neuropsychiatric disorders in childhood. Transcranial magnetic stimulation studies based on muscle responses (motor-evoked potentials) suggested that reduced motor inhibition contributes to hyperactivity, a core symptom of the disease. Here we employed the N100 component of the…

Observational Learning in Mice Can Be Prevented by Medial Prefrontal Cortex Stimulation and Enhanced by Nucleus Accumbens Stimulation

ERIC Educational Resources Information Center

Jurado-Parras, M. Teresa; Gruart, Agnes; Delgado-Garcia, Jose M.

2012-01-01

The neural structures involved in ongoing appetitive and/or observational learning behaviors remain largely unknown. Operant conditioning and observational learning were evoked and recorded in a modified Skinner box provided with an on-line video recording system. Mice improved their acquisition of a simple operant conditioning task by…

A new method for registration of kinesthetic evoked potentials for studies of proprioceptive sensitivity in normal subjects and patients with organic lesions in the brain.

PubMed

Gordeev, S A; Voronin, S G

2015-01-01

The proprioceptive sensitivity of healthy volunteers and convalescents after acute cerebrovascular episodes was studied by a new neurophysiological method for registration of kinesthetic evoked potentials emerging in response to passive 50(o) bending of the hand in the wrist joint with the angular acceleration of 350 rad/sec(2). Kinesthetic evoked potentials were recorded above the somatosensory cortex projection areas in the hemispheres contra- and ipsilateral to the stimulated limb. The patients exhibited significantly longer latencies and lesser amplitudes of the early components of response in the involved hemisphere in comparison with normal subjects. The method for registration of the kinesthetic evoked potentials allows a more detailed study of the mechanisms of kinesthetic sensitivity in health and in organic involvement of the brain.

Effects of coil orientation and magnetic field shield on transcranial magnetic stimulation in cats.

PubMed

Nakatoh, S; Kitagawa, H; Kawaguchi, Y; Nakamura, H; Takano, H; Tsuji, H

1998-09-01

To obtain suitable stimulus conditions for transcranial magnetic stimulation, the evoked compound muscle action potential (ECMAP), evoked spinal cord potential (ESCP), and magnetic and electric fields were analyzed in cats with and without the use of a magnetic field shield. Cats were stimulated using a figure 8 magnetic coil placed on the cranium above the motor cortex. The maximum ECMAP amplitude was recorded when the electric current in the coil was in the mediolateral direction, regardless of whether a magnetic shield with a 5 x 5 cm window was used. ECMAP and ESCP thresholds were reduced when magnetic shielding was in place. Due to the edge effect, the strengths of the magnetic and electric fields were highest in the brainstem area, which is an inhomogeneous volume conductor of the cat's cranium. A large induced electric field directed caudally elicited ECMAP and ESCP responses effectively when a magnetic shield with a 5 x 5 cm window was in place.

Selectivity of conventional electrodes for recording motor evoked potentials: An investigation with high-density surface electromyography.

PubMed

Gallina, Alessio; Peters, Sue; Neva, Jason L; Boyd, Lara A; Garland, S Jayne

2017-06-01

The objective of this study was to determine whether motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation and measured with conventional bipolar electromyography (EMG) are influenced by crosstalk from non-target muscles. MEPs were recorded in healthy participants using conventional EMG electrodes placed over the extensor carpi radialis muscle (ECR) and high-density surface EMG (HDsEMG). Fifty MEPs at 120% resting and active motor threshold were recorded. To determine the contribution of ECR to the MEPs, the amplitude distribution across HDsEMG channels was correlated with EMG activity recorded during a wrist extension task. Whereas the conventional EMG identified MEPs from ECR in >90% of the stimulations, HDsEMG revealed that spatial amplitude distribution representative of ECR activation was observed less frequently at rest than while holding a contraction (P < 0.001). MEPs recorded with conventional EMG may contain crosstalk from non-target muscles, especially when the stimulation is applied at rest. Muscle Nerve 55: 828-834, 2017. © 2016 Wiley Periodicals, Inc.

[A wireless smart home system based on brain-computer interface of steady state visual evoked potential].

PubMed

Zhao, Li; Xing, Xiao; Guo, Xuhong; Liu, Zehua; He, Yang

2014-10-01

Brain-computer interface (BCI) system is a system that achieves communication and control among humans and computers and other electronic equipment with the electroencephalogram (EEG) signals. This paper describes the working theory of the wireless smart home system based on the BCI technology. We started to get the steady-state visual evoked potential (SSVEP) using the single chip microcomputer and the visual stimulation which composed by LED lamp to stimulate human eyes. Then, through building the power spectral transformation on the LabVIEW platform, we processed timely those EEG signals under different frequency stimulation so as to transfer them to different instructions. Those instructions could be received by the wireless transceiver equipment to control the household appliances and to achieve the intelligent control towards the specified devices. The experimental results showed that the correct rate for the 10 subjects reached 100%, and the control time of average single device was 4 seconds, thus this design could totally achieve the original purpose of smart home system.

Spinal cord stimulation paresthesia and activity of primary afferents.

PubMed

North, Richard B; Streelman, Karen; Rowland, Lance; Foreman, P Jay

2012-10-01

A patient with failed back surgery syndrome reported paresthesia in his hands and arms during a spinal cord stimulation (SCS) screening trial with a low thoracic electrode. The patient's severe thoracic stenosis necessitated general anesthesia for simultaneous decompressive laminectomy and SCS implantation for chronic use. Use of general anesthesia gave the authors the opportunity to characterize the patient's unusual distribution of paresthesia. During SCS implantation, they recorded SCS-evoked antidromic potentials at physiologically relevant amplitudes in the legs to guide electrode placement and in the arms as controls. Stimulation of the dorsal columns at T-8 evoked potentials in the legs (common peroneal nerves) and at similar thresholds, consistent with the sensation of paresthesia in the arms, in the right ulnar nerve. The authors' electrophysiological observations support observations by neuroanatomical specialists that primary afferents can descend several (in this case, at least 8) vertebral segments in the spinal cord before synapsing or ascending. This report thus confirms a physiological basis for unusual paresthesia distribution associated with thoracic SCS.

Spontaneous firing and evoked responses of spinal nociceptive neurons are attenuated by blockade of P2X3 and P2X2/3 receptors in inflamed rats.

PubMed

Xu, Jun; Chu, Katharine L; Brederson, Jill-Desiree; Jarvis, Michael F; McGaraughty, Steve

2012-08-01

P2X3 and P2X2/3 receptors are selectively expressed on primary afferent nociceptors and have been implicated in modulating nociception in different models of pathological pain, including inflammatory pain. In an effort to delineate further the role of P2X3 receptors (homomeric and heteromeric) in the modulation of nociceptive transmission after a chronic inflammation injury, A-317491, a potent and selective P2X3-P2X2/3 antagonist, was administered to CFA-inflamed rats in order to examine its effects on responses of spinal dorsal horn neurons to mechanical and thermal stimulation. Systemic injection of A-317491 (30 μmol/kg, i.v.) reduced the responses of wide-dynamic-range (WDR) and nociceptive specific (NS) neurons to both high-intensity mechanical (pinch) and heat (49°C) stimulation. A-317491 also decreased low-intensity (10 g von Frey hair) mechanically evoked activity of WDR neurons but did not alter WDR neuronal responses to cold stimulation (5°C). Spontaneous firing of WDR neurons in CFA-inflamed rats was also significantly attenuated by A-317491 injection. By using immunohistochemistry, P2X3 receptors were demonstrated to be enhanced in lamina II of the spinal dorsal horn after inflammation. In summary, blockade of P2X3 and P2X2/3 receptors dampens mechanical- and heat-related signaling, as well as nonevoked activity of key classes of spinal nociceptive neurons in inflamed animals. These data suggest that P2X3 and/or P2X2/3 receptors have a broad contribution to somatosensory/nociceptive transmission in rats with a chronic inflammatory injury and are consistent with previous behavioral data demonstrating antiallodynic and antihyperalgesic effects of receptor antagonists. Copyright © 2012 Wiley Periodicals, Inc.

Human cerebral potentials evoked by moving dynamic random dot stereograms.

PubMed

Herpers, M J; Caberg, H B; Mol, J M

1981-07-01

In 11 normal healthy human subjects an evoked potential was elicited by moving dynamic random dot stereograms. The random dots were generated by a minicomputer. An average of each of 8 EEG channels of the subjects tested was made. The maximum of the cerebral evoked potentials thus found was localized in the central and parietal region. No response earlier than 130--150 msec after the stimulus could be proved. The influence of fixation, the number of dots provided, an interocular interstimulus interval in the presentation of the dots, and lense accommodation movements on the evoked stereoptic potentials was investigated and discussed. An interocular interstimulus interval (left eye leading) in the presentation of the dots caused an increase in latency of the response much longer than the imposed interstimulus interval itself. It was shown that no accommodation was needed to perceive the depth impression, and to evoke the cerebral response with random dot stereograms. There are indications of an asymmetry between the two hemispheres in the handling of depth perception after 250 msec. The potential distribution of the evoked potentials strongly suggests that they are not generated in the occipital region.

Activity-Dependence of Synaptic Vesicle Dynamics

PubMed Central

Forte, Luca A.

2017-01-01

The proper function of synapses relies on efficient recycling of synaptic vesicles. The small size of synaptic boutons has hampered efforts to define the dynamical states of vesicles during recycling. Moreover, whether vesicle motion during recycling is regulated by neural activity remains largely unknown. We combined nanoscale-resolution tracking of individual synaptic vesicles in cultured hippocampal neurons from rats of both sexes with advanced motion analyses to demonstrate that the majority of recently endocytosed vesicles undergo sequences of transient dynamical states including epochs of directed, diffusional, and stalled motion. We observed that vesicle motion is modulated in an activity-dependent manner, with dynamical changes apparent in ∼20% of observed boutons. Within this subpopulation of boutons, 35% of observed vesicles exhibited acceleration and 65% exhibited deceleration, accompanied by corresponding changes in directed motion. Individual vesicles observed in the remaining ∼80% of boutons did not exhibit apparent dynamical changes in response to stimulation. More quantitative transient motion analyses revealed that the overall reduction of vesicle mobility, and specifically of the directed motion component, is the predominant activity-evoked change across the entire bouton population. Activity-dependent modulation of vesicle mobility may represent an important mechanism controlling vesicle availability and neurotransmitter release. SIGNIFICANCE STATEMENT Mechanisms governing synaptic vesicle dynamics during recycling remain poorly understood. Using nanoscale resolution tracking of individual synaptic vesicles in hippocampal synapses and advanced motion analysis tools we demonstrate that synaptic vesicles undergo complex sets of dynamical states that include epochs of directed, diffusive, and stalled motion. Most importantly, our analyses revealed that vesicle motion is modulated in an activity-dependent manner apparent as the reduction in overall vesicle mobility in response to stimulation. These results define the vesicle dynamical states during recycling and reveal their activity-dependent modulation. Our study thus provides fundamental new insights into the principles governing synaptic function. PMID:28954868

The Role of Auditory Evoked Potentials in the Context of Cochlear Implant Provision.

PubMed

Hoth, Sebastian; Dziemba, Oliver Christian

2017-12-01

: Auditory evoked potentials (AEP) are highly demanded during the whole process of equipping patients with cochlear implants (CI). They play an essential role in preoperative diagnostics, intraoperative testing, and postoperative monitoring of auditory performance and success. The versatility of AEP's is essentially enhanced by their property to be evokable by acoustic as well as electric stimuli. Thus, the electric responses of the auditory system following acoustic stimulation and recorded by the conventional surface technique as well as by transtympanic derivation from the promontory (Electrocochleography [ECochG]) are used for the quantitative determination of hearing loss and, additionally, electrically evoked compound actions potentials (ECAP) can be recorded with the intracochlear electrodes of the implant just adjacent to the stimulation electrode to check the functional integrity of the device and its coupling to the auditory system. The profile of ECAP thresholds is used as basis for speech processor fitting, the spread of excitation (SOE) allows the identification of electrode mislocations such as array foldover, and recovery functions may serve to optimize stimulus pulse rate. These techniques as well as those relying on scalp surface activity originating in the brainstem or the auditory cortex accompany the CI recipient during its whole life span and they offer valuable insights into functioning and possible adverse effects of the CI for clinical and scientific purposes.

D-amphetamine (A)-induced dopamine (DA) release is not strictly dependent on newly-synthesized transmitter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, E.; Cubeddu, L.

1986-03-05

A is thought to exert its stimulant effects by releasing DA from a newly synthesized transmitter pool. This hypothesis was evaluated directly by measuring the basal efflux and electrically-evoked release of endogenous DA and dihydroxyphenylacetic acid (DOPAC). In striatal slices from reserpine-treated rabbits A increased DA efflux, reduced DOPAC efflux, and inhibited electrically-evoked /sup 3/H-ACh release in a concentration-dependent manner. These effects could not be mimicked by inhibition of neuronal uptake or MAO, but were blocked by inhibition of DA synthesis or neuronal uptake, and were potentiated by inhibition of MAO. In slices with intact vesicular transmitter stores A inducedmore » DA efflux was 2-fold greater than that seen in slices having no vesicular stores. Inhibition of DA synthesis reduced A-induced DA efflux by 60%, but had little effect on the ability of A to inhibit /sup 3/H-ACh release. A also increased the electrical stimulation-evoked overflow of DA (an effect which was attenuated slightly by synthesis inhibition), and potently inhibited DOPAC overflow. These results suggest that: 1) A facilitates efflux of axoplasmic DA by an accelerated exchange diffusion mechanism. The releasable axoplasmic pool is derived from newly synthesized and vesicular transmitter pools; 2) postsynaptic indices of transmitter release may be misleading; and 3) A increases electrically-evoked DA release possibly by inhibiting neuronal uptake.« less

Jaw-opening reflex and corticobulbar motor excitability changes during quiet sleep in non-human primates.

PubMed

Yao, Dongyuan; Lavigne, Gilles J; Lee, Jye-Chang; Adachi, Kazunori; Sessle, Barry J

2013-02-01

To test the hypothesis that the reflex and corticobulbar motor excitability of jaw muscles is reduced during sleep. Polysomnographic recordings in the electrophysiological study. University sleep research laboratories. The reflex and corticobulbar motor excitability of jaw muscles was determined during the quiet awake state (QW) and quiet sleep (QS) in monkeys (n = 4). During QS sleep, compared to QW periods, both tongue stimulation-evoked jaw-opening reflex peak and root mean square amplitudes were significantly decreased with stimulations at 2-3.5 × thresholds (P < 0.001). The jaw-opening reflex latency during sleep was also significantly longer than during QW. Intracortical microstimulation (ICMS) within the cortical masticatory area induced rhythmic jaw movements at a stable threshold (≤ 60 μA) during QW; but during QS, ICMS failed to induce any rhythmic jaw movements at the maximum ICMS intensity used, although sustained jaw-opening movements were evoked at significantly increased threshold (P < 0.001) in one of the monkeys. Similarly, during QW, ICMS within face primary motor cortex induced orofacial twitches at a stable threshold (≤ 35 μA), but the ICMS thresholds were elevated during QS. Soon after the animal awoke, rhythmic jaw movements and orofacial twitches could be evoked at thresholds similar to those before QS. The results suggest that the excitability of reflex and corticobulbar-evoked activity in the jaw motor system is depressed during QS.

Functional anatomy of vagina muscles in the blood-feeding insect, Rhodnius prolixus.

PubMed

Chiang, R G; O'Donnell, M J

2009-11-01

The physiology of the muscles associated with the vagina in the blood-feeding insect, Rhodnius prolixus Stal, was investigated with the use of Methylene Blue staining to visualize the anatomy, and a micro force transducer to record spontaneous and neurally-evoked contractions. The vagina is associated with a dorsal muscle and a set of paired lateral muscles. The dorsal muscle extends from the base of the common oviduct to apodemes located laterally on sternite VIII, the first genital segment. The lateral muscles extend from a medially-located apodeme on the posterior edge of sternite VI around each side of the common oviduct to travel posteriorly along the side of the vagina before inserting laterally on apodemes on sternite VIII. The vagina muscles display spontaneous and neurally-evoked contractions that are prolonged but transient. The response to evoked contractions shows that the muscles are innervated by both excitatory and inhibitory motor axons. The degree of tension generated by evoked contractions is dependent on the frequency of stimulation with maximal tension being generated at 20-30Hz. This tension, which often exceeds 400mg, is transient and returns to a baseline within 1 to 2min during continuous stimulation. These results, which are the first to describe this chamber in this well-studied insect, are discussed with respect to the act of egg laying.

Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A.

PubMed

Otsuka, M; Yoshioka, K; Yanagisawa, M; Suzuki, H; Zhao, F Y; Guo, J Z; Hosoki, R; Kurihara, T

1995-07-01

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.

Topography of eye-position sensitivity of saccades evoked electrically from the cat's superior colliculus.

PubMed

McIlwain, J T

1990-03-01

Saccades evoked electrically from the deep layers of the superior colliculus have been examined in the alert cat with its head fixed. Amplitudes of the vertical and horizontal components varied linearly with the starting position of the eye. The slopes of the linear-regression lines provided an estimate of the sensitivity of these components to initial eye position. In observations on 29 sites in nine cats, the vertical and horizontal components of saccades evoked from a given site were rarely influenced to the same degree by initial eye position. For most sites, the horizontal component was more sensitive than the vertical component. Sensitivities of vertical and horizontal components were lowest near the representations of the horizontal and vertical meridians, respectively, of the collicular retinotopic map, but otherwise exhibited no systematic retinotopic dependence. Estimates of component amplitudes for saccades evoked from the center of the oculomotor range also diverged significantly from those predicted from the retinotopic map. The results of this and previous studies indicate that electrical stimulation of the cat's superior colliculus cannot yield a unique oculomotor map or one that is in register everywhere with the sensory retinotopic map. Several features of these observations suggest that electrical stimulation of the colliculus produces faulty activation of a saccadic control system that computes target position with respect to the head and that small and large saccades are controlled differently.

The temporal relationship between non-respiratory burst activity of expiratory laryngeal motoneurons and phrenic apnoea during stimulation of the superior laryngeal nerve in rat

PubMed Central

Sun, Qi-Jian; Bautista, Tara G; Berkowitz, Robert G; Zhao, Wen-Jing; Pilowsky, Paul M

2011-01-01

Abstract A striking effect of stimulating the superior laryngeal nerve (SLN) is its ability to inhibit central inspiratory activity (cause ‘phrenic apnoea’), but the mechanism underlying this inhibition remains unclear. Here we demonstrate, by stimulating the SLN at varying frequencies, that the evoked non-respiratory burst activity recorded from expiratory laryngeal motoneurons (ELMs) has an intimate temporal relationship with phrenic apnoea. During 1–5 Hz SLN stimulation, occasional absences of phrenic nerve discharge (PND) occurred such that every absent PND was preceded by an ELM burst activity. During 10–20 Hz SLN stimulation, more bursts were evoked together with more absent PNDs, leading eventually to phrenic apnoea. Interestingly, subsequent microinjections of isoguvacine (10 mm, 20–40 nl) into ipsilateral Bötzinger complex (BötC) and contralateral nucleus tractus solitarii (NTS) significantly attenuated the apnoeic response but not the ELM burst activity. Our results suggest a bifurcating projection from NTS to both the caudal nucleus ambiguus and BötC, which mediates the closely related ELM burst and apnoeic response, respectively. We believe that such an intimate timing between laryngeal behaviour and breathing is crucial for the effective elaboration of the different airway protective behaviours elicited following SLN stimulation, including the laryngeal adductor reflex, swallowing and cough. PMID:21320890

Properties and connections of cat fastigiospinal neurons.

PubMed

Wilson, V J; Uchino, Y; Maunz, R A; Susswein, A; Fukushima, K

1978-05-12

1. Neurons in the cat fastigial nucleus that project to the upper cervical spinal segments (fastigiospinal neurons) were fired by antidromic stimulation of the contralateral spinal cord. Dye ejection from the recording electrode was used to show that most neurons were in the rostral half of the fastigial nucleus. 2. Fastigiospinal neurons can be excited and/or inhibited by stimulation of forelimb and hindlimb nerves and by stimulation of the vestibular nerve. These inputs converge on many neurons. 3. Antidromic microstimulation was used to trace fastigiospinal axons to the vicinity of motor nuclei in in C2-C3. 4. The rostral fastigial nucleus was stimulated in preparations with the medial longitudinal fasciculus transected by a wide lesion that impinged on the medial reticular formation in the caudal medulla, to eliminate some potential axon reflexes. Short-latency EPSPs were recorded in some trapezius and biventer-cervicis motoneurons. In many cases there was little or no occlusion between these EPSPs and others evoked by stimulation of the vestibular nerve ipsilateral to the motoneurons. 5. Movement of the stimulating electrode and placement of this electrode lateral to the fastigial nucleus show that the zone from which low threshold EPSPs can be evoked is localized. 6. Latency measurements and lack of temporal facilitation with double shocks suggest that the EPSPs are monosynaptic. The evidence suggests that they are caused by fastigiospinal fibers terminating on motoneurons.

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

PubMed

Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

2012-06-25

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

Modulation of electric brain responses evoked by pitch deviants through transcranial direct current stimulation.

PubMed

Royal, Isabelle; Zendel, Benjamin Rich; Desjardins, Marie-Ève; Robitaille, Nicolas; Peretz, Isabelle

2018-01-31

Congenital amusia is a neurodevelopmental disorder, characterized by a difficulty detecting pitch deviation that is related to abnormal electrical brain responses. Abnormalities found along the right fronto-temporal pathway between the inferior frontal gyrus (IFG) and the auditory cortex (AC) are the likely neural mechanism responsible for amusia. To investigate the causal role of these regions during the detection of pitch deviants, we applied cathodal (inhibitory) transcranial direct current stimulation (tDCS) over right frontal and right temporal regions during separate testing sessions. We recorded participants' electrical brain activity (EEG) before and after tDCS stimulation while they performed a pitch change detection task. Relative to a sham condition, there was a decrease in P3 amplitude after cathodal stimulation over both frontal and temporal regions compared to pre-stimulation baseline. This decrease was associated with small pitch deviations (6.25 cents), but not large pitch deviations (200 cents). Overall, this demonstrates that using tDCS to disrupt regions around the IFG and AC can induce temporary changes in evoked brain activity when processing pitch deviants. These electrophysiological changes are similar to those observed in amusia and provide causal support for the connection between P3 and fronto-temporal brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cortical modulation of the nucleus of the optic tract in the rabbit.

PubMed

Pettorossi, V E; Troiani, D

1983-09-01

We analyzed in rabbits the relationships between the temporooccipital nystagmogenic cortex (NGC)--the region sited at the border between cortical areas 17, 21, and 22--and the nucleus of the optic tract (NOT). Two experimental approaches were used: (a) eye movement analysis before and after electrolytic lesion of the NOT region provided an indication of the importance of the NOT for the interaction between the ocular nystagmus elicited by natural optokinetic stimulation (OKN) and the nystagmus evoked by electrical stimulation of the nystagmogenic area; (b) NOT direction-selective and velocity-sensitive units were tested with single shock or repetitive electrical stimulation of the nystagmogenic region. Single-shock stimulation evoked single or multiple spikes in 50% of NOT units analyzed and repetitive stimuli induced prolonged facilitation and inhibitory rebounds in 70% of the units tested. Comparison of orthodromic activation latencies of the NOT cells (3.2 and 6.1 ms) after cortical stimulation and of antidromic activation latencies of cortical nystagmogenic units (2.6 ms) after NOT shocks, suggested monosynaptic as well as polysynaptic connections between the temporooccipital cortex and the NOT. The existence of such cortical-NOT linkage indicates that the NOT is intercalated between the cortex and the oculomotor centers and represents the most probable site of interaction of the cortical nystagmus pathway with the optokinetic reflex arc.

Vibration-Induced Kinesthetic Illusions and Corticospinal Excitability Changes.

PubMed

Mancheva, Kapka; Rollnik, Jens D; Wolf, Werner; Dengler, Reinhard; Kossev, Andon

2017-01-01

The authors' aim was to investigate the changes of corticospinal excitability during kinesthetic illusions induced by tendon vibration. Motor-evoked potentials in response to transcranial magnetic stimulation were recorded from the vibrated flexor carpi radialis and its antagonist, extensor carpi radialis. The illusions were evoked under vision conditions without feedback for the position of the wrist (open or closed eyes). In these two conditions motor-evoked potential changes during vibration in the antagonist were not identical. This discrepancy may be a result of 2 simultaneously acting, different and opposite influences and the balance between them depends on visual conditions. Thus, the illusion was accompanied by the facilitation of corticospinal excitability in both vibrated muscle and its antagonist.

Multifocal visual evoked responses to dichoptic stimulation using virtual reality goggles: Multifocal VER to dichoptic stimulation.

PubMed

Arvind, Hemamalini; Klistorner, Alexander; Graham, Stuart L; Grigg, John R

2006-05-01

Multifocal visual evoked potentials (mfVEPs) have demonstrated good diagnostic capabilities in glaucoma and optic neuritis. This study aimed at evaluating the possibility of simultaneously recording mfVEP for both eyes with dichoptic stimulation using virtual reality goggles and also to determine the stimulus characteristics that yield maximum amplitude. ten healthy volunteers were recruited and temporally sparse pattern pulse stimuli were presented dichoptically using virtual reality goggles. Experiment 1 involved recording responses to dichoptically presented checkerboard stimuli and also confirming true topographic representation by switching off specific segments. Experiment 2 involved monocular stimulation and comparison of amplitude with Experiment 1. In Experiment 3, orthogonally oriented gratings were dichoptically presented. Experiment 4 involved dichoptic presentation of checkerboard stimuli at different levels of sparseness (5.0 times/s, 2.5 times/s, 1.66 times/s and 1.25 times/s), where stimulation of corresponding segments of two eyes were separated by 16.7, 66.7,116.7 & 166.7 ms respectively. Experiment 1 demonstrated good traces in all regions and confirmed topographic representation. However, there was suppression of amplitude of responses to dichoptic stimulation by 17.9+/-5.4% compared to monocular stimulation. Experiment 3 demonstrated similar suppression between orthogonal and checkerboard stimuli (p = 0.08). Experiment 4 demonstrated maximum amplitude and least suppression (4.8%) with stimulation at 1.25 times/s with 166.7 ms separation between eyes. It is possible to record mfVEP for both eyes during dichoptic stimulation using virtual reality goggles, which present binocular simultaneous patterns driven by independent sequences. Interocular suppression can be almost eliminated by using a temporally sparse stimulus of 1.25 times/s with a separation of 166.7 ms between stimulation of corresponding segments of the two eyes.

Protein kinase C activates non-capacitative calcium entry in human platelets

PubMed Central

Rosado, Juan A; Sage, Stewart O

2000-01-01

In many non-excitable cells Ca2+ influx is mainly controlled by the filling state of the intracellular Ca2+ stores. It has been suggested that this store-mediated or capacitative Ca2+ entry is brought about by a physical and reversible coupling of the endoplasmic reticulum with the plasma membrane. Here we provide evidence for an additional, non-capacitative Ca2+ entry mechanism in human platelets. Changes in cytosolic Ca2+ and Sr2+ were measured in human platelets loaded with the fluorescent indicator fura-2. Depletion of the internal Ca2+ stores with thapsigargin plus a low concentration of ionomycin stimulated store-mediated cation entry, as demonstrated upon Ca2+ or Sr2+ addition. Subsequent treatment with thrombin stimulated further divalent cation entry in a concentration-dependent manner. Direct activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate or 1-oleoyl-2-acetyl-sn-glycerol also stimulated divalent cation entry, without evoking the release of Ca2+ from intracellular stores. Cation entry evoked by thrombin or activators of PKC was abolished by the PKC inhibitor Ro-31-8220. Unlike store-mediated Ca2+ entry, jasplakinolide, which reorganises actin filaments into a tight cortical layer adjacent to the plasma membrane, did not inhibit divalent cation influx evoked by thrombin when applied after Ca2+ store depletion, or by activators of PKC. Thrombin also activated Ca2+ entry in platelets in which the release from intracellular stores and store-mediated Ca2+ entry were blocked by xestospongin C. These results indicate that the non-capacitative divalent cation entry pathway is regulated independently of store-mediated entry and does not require coupling of the endoplasmic reticulum and the plasma membrane. These results support the existence of a mechanism for receptor-evoked Ca2+ entry in human platelets that is independent of Ca2+ store depletion. This Ca2+ entry mechanism may be activated by occupation of G-protein-coupled receptors, which activate PKC, or by direct activation of PKC, thus generating non-capacitative Ca2+ entry alongside that evoked following the release of Ca2+ from the intracellular stores. PMID:11080259

Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

NASA Astrophysics Data System (ADS)

Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

2015-03-01

Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

Auditory Evoked Responses in Neonates by MEG

NASA Astrophysics Data System (ADS)

Hernandez-Pavon, J. C.; Sosa, M.; Lutter, W. J.; Maier, M.; Wakai, R. T.

2008-08-01

Magnetoencephalography is a biomagnetic technique with outstanding potential for neurodevelopmental studies. In this work, we have used MEG to determinate if newborns can discriminate between different stimuli during the first few months of life. Five neonates were stimulated during several minutes with auditory stimulation. The results suggest that the newborns are able to discriminate between different stimuli despite their early age.

Auditory Evoked Responses in Neonates by MEG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernandez-Pavon, J. C.; Department of Medical Physics, University of Wisconsin Madison, Wisconsin; Sosa, M.

2008-08-11

Magnetoencephalography is a biomagnetic technique with outstanding potential for neurodevelopmental studies. In this work, we have used MEG to determinate if newborns can discriminate between different stimuli during the first few months of life. Five neonates were stimulated during several minutes with auditory stimulation. The results suggest that the newborns are able to discriminate between different stimuli despite their early age.

Changes of Excitability in M1 Induced by Neuromuscular Electrical Stimulation Differ Between Presence and Absence of Voluntary Drive

ERIC Educational Resources Information Center

Sugawara, Kenichi; Tanabe, Shigeo; Higashi, Toshio; Tsurumi, Takamasa; Kasai, Tatsuya

2011-01-01

The aim of this study is to investigate excitability changes in the human motor cortex induced by variable therapeutic electrical stimulations (TESs) with or without voluntary drive. We recorded motor-evoked potentials (MEPs) from extensor and flexor carpi radialis (FCR) muscles at rest and during FCR muscle contraction after the application of…

Synchronized Astrocytic Ca2+ Responses in Neurovascular Coupling during Somatosensory Stimulation and for the Resting State.

PubMed

Gu, Xiaochun; Chen, Wei; Volkow, Nora D; Koretsky, Alan P; Du, Congwu; Pan, Yingtian

2018-06-26

The role of astrocytes in neurovascular coupling (NVC) is unclear. Here, we applied a multimodality imaging approach to concomitantly measure synchronized neuronal or astrocytic Ca 2+ and hemodynamic changes in the mouse somatosensory cortex at rest and during sensory electrical stimulation. Strikingly, we found that low-frequency stimulation (0.3-1 Hz), which consistently evokes fast neuronal Ca 2+ transients (6.0 ± 2.7 ms latency) that always precede vascular responses, does not always elicit astrocytic Ca 2+ transients (313 ± 65 ms latency). However, the magnitude of the hemodynamic response is increased when astrocytic transients occur, suggesting a facilitatory role of astrocytes in NVC. High-frequency stimulation (5-10 Hz) consistently evokes a large, delayed astrocytic Ca 2+ accumulation (3.48 ± 0.09 s latency) that is temporarily associated with vasoconstriction, suggesting a role for astrocytes in resetting NVC. At rest, neuronal, but not astrocytic, Ca 2+ fluctuations correlate with hemodynamic low-frequency oscillations. Taken together, these results support a role for astrocytes in modulating, but not triggering, NVC. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Neurophysiological responses to unpleasant stimuli (acute electrical stimulations and emotional pictures) are increased in patients with schizophrenia

PubMed Central

Duval, Céline Z.; Goumon, Yannick; Kemmel, Véronique; Kornmeier, Jürgen; Dufour, André; Andlauer, Olivier; Vidailhet, Pierre; Poisbeau, Pierrick; Salvat, Eric; Muller, André; Mensah-Nyagan, Ayikoé G.; Schmidt-Mutter, Catherine; Giersch, Anne

2016-01-01

Patients with schizophrenia have often been described as insensitive to nociceptive signals, but objective evidence is sparse. We address this question by combining subjective behavioral and objective neurochemical and neurophysiological measures. The present study involved 21 stabilized and mildly symptomatic patients with schizophrenia and 21 control subjects. We applied electrical stimulations below the pain threshold and assessed sensations of pain and unpleasantness with rating scales, and Somatosensory Evoked Potentials (SEPs/EEG). We also measured attention, two neurochemical stress indices (ACTH/cortisol), and subjective VEPs/EEG responses to visual emotional stimuli. Our results revealed that, subjectively, patients’ evaluations do not differ from controls. However, the amplitude of EEG evoked potentials was greater in patients than controls as early as 50 ms after electrical stimulations and beyond one second after visual processing of emotional pictures. Such responses could not be linked to the stress induced by the stimulations, since stress hormone levels were stable. Nor was there a difference between patients and controls in respect of attention performance and tactile sensitivity. Taken together, all indices measured in patients in our study were either heightened or equivalent relative to healthy volunteers. PMID:26935652

Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome

PubMed Central

Best, Tyler K.; Cramer, Nathan P.; Chakrabarti, Lina; Haydar, Tarik F.; Galdzicki, Zygmunt

2013-01-01

GABAergic dysfunction is implicated in hippocampal deficits of the Ts65Dn mouse model of Down syndrome (DS). Since Ts65Dn mice overexpress G-protein coupled inward-rectifying potassium (GIRK2) containing channels, we sought to evaluate whether increased GABAergic function disrupts the functioning of hippocampal circuitry. After confirming that GABAB/GIRK current density is significantly elevated in Ts65Dn CA1 pyramidal neurons, we compared monosynaptic inhibitory inputs in CA1 pyramidal neurons in response to proximal (stratum radiatum; SR) and distal (stratum lacunosum moleculare; SLM) stimulation of diploid and Ts65Dn acute hippocampal slices. Synaptic GABAB and GABAA mediated currents evoked by SR stimulation were generally unaffected in Ts65Dn CA1 neurons. However, the GABAB/GABAA ratios evoked by stimulation within the SLM of Ts65Dn hippocampus were significantly larger in magnitude, consistent with increased GABAB/GIRK currents after SLM stimulation. These results indicate that GIRK overexpression in Ts65Dn has functional consequences which affect the balance between GABAB and GABAA inhibition of CA1 pyramidal neurons, most likely in a pathway specific manner, and may contribute to cognitive deficits reported in these mice. PMID:22178330

Augmented Central Pain Processing in Vulvodynia

PubMed Central

Hampson, Johnson P.; Reed, Barbara D.; Clauw, Daniel J.; Bhavsar, Rupal; Gracely, Richard H.; Haefner, Hope K.; Harris, Richard E.

2013-01-01

Vulvodynia (VVD) is a chronic pain disorder, wherein women display sensitivity to evoked stimuli at the vulva and/or spontaneous vulvar pain. Our previous work suggests generalized hyperalgesia in this population, however little is known about central neurobiological factors that may influence pain in VVD. Here we investigated local (vulvar) and remote (thumb) pressure evoked pain processing in 24 VVD patients compared to 13 age-matched, pain-free healthy controls (HC). As a positive control we also examined thumb pressure pain in 24 fibromyalgia (FM) patients. The VVD and FM patients displayed overlapping insular brain activations that were greater than HC, in response to thumb stimulation (P<0.005 corrected). Compared to HC, VVD participants displayed greater levels of activation during thumb stimulation within the insula, dorsal mid-cingulate, posterior cingulate and thalamus (P<0.005 corrected). Significant differences between VVD subgroups (primary versus secondary and provoked versus unprovoked) were seen within the posterior cingulate with thumb stimulation, and within the precuneus region with vulvar stimulation (provoked versus unprovoked only). The augmented brain activation in VVD patients in response to a stimulus remote from the vulva suggests central neural pathology in this disorder. Moreover, differing central activity between VVD subgroups suggests heterogeneous pathologies within this diagnosis. PMID:23578957

Curcumin inhibits amygdaloid kindled seizures in rats.

PubMed

DU, Peng; Li, Xin; Lin, Hao-Jie; Peng, Wei-Feng; Liu, Jian-Ying; Ma, Yu; Fan, Wei; Wang, Xin

2009-06-20

Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses. Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds). Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.

Direct recordings from the auditory cortex in a cochlear implant user.

PubMed

Nourski, Kirill V; Etler, Christine P; Brugge, John F; Oya, Hiroyuki; Kawasaki, Hiroto; Reale, Richard A; Abbas, Paul J; Brown, Carolyn J; Howard, Matthew A

2013-06-01

Electrical stimulation of the auditory nerve with a cochlear implant (CI) is the method of choice for treatment of severe-to-profound hearing loss. Understanding how the human auditory cortex responds to CI stimulation is important for advances in stimulation paradigms and rehabilitation strategies. In this study, auditory cortical responses to CI stimulation were recorded intracranially in a neurosurgical patient to examine directly the functional organization of the auditory cortex and compare the findings with those obtained in normal-hearing subjects. The subject was a bilateral CI user with a 20-year history of deafness and refractory epilepsy. As part of the epilepsy treatment, a subdural grid electrode was implanted over the left temporal lobe. Pure tones, click trains, sinusoidal amplitude-modulated noise, and speech were presented via the auxiliary input of the right CI speech processor. Additional experiments were conducted with bilateral CI stimulation. Auditory event-related changes in cortical activity, characterized by the averaged evoked potential and event-related band power, were localized to posterolateral superior temporal gyrus. Responses were stable across recording sessions and were abolished under general anesthesia. Response latency decreased and magnitude increased with increasing stimulus level. More apical intracochlear stimulation yielded the largest responses. Cortical evoked potentials were phase-locked to the temporal modulations of periodic stimuli and speech utterances. Bilateral electrical stimulation resulted in minimal artifact contamination. This study demonstrates the feasibility of intracranial electrophysiological recordings of responses to CI stimulation in a human subject, shows that cortical response properties may be similar to those obtained in normal-hearing individuals, and provides a basis for future comparisons with extracranial recordings.

Interaction of corneal nociceptive stimulation and lacrimal secretion.

PubMed

Situ, Ping; Simpson, Trefford L

2010-11-01

To investigate the interaction between corneal stimuli at different positions and tear secretion and to establish relationships between nociceptive stimuli detection thresholds and stimulated tearing. Using a computerized Belmonte-esthesiometer, mechanical and chemical stimuli, from 0% to 200% of the threshold in 50% steps, were delivered (in random order) to the central and peripheral (approximately 2-mm inside the limbus) cornea during four separate sessions to 15 subjects. Immediately after each stimulus, tear meniscus height (TMH) was measured using optical coherence tomography to quantify the amount of lacrimal secretion, and subjects reported whether they felt tears starting to accumulate in their eyes. Thresholds (50% detection) for detection of tearing were estimated. TMH increased with increasing stimulus intensity (P < 0.05), and the overall increase was higher with central stimulation than with peripheral stimulation (P < 0.05). The changes in TMH with threshold-scaled stimulus intensity depended on test location (P < 0.05) and stimulus modality (P < 0.05). The maximum intensity of mechanical stimulation of the central cornea induced the greatest TMH (all P < 0.05). For chemical stimulation, the stimulus intensity required to induce detectable tearing was higher than that required to detect a stimulus and higher in the periphery than at the center (all P < 0.05). Noxious mechanical and chemical stimuli evoked measurable tear secretion, with central corneal mechanical stimulation evoking the strongest lacrimation reflex. Central mechanical corneal stimulation is the most effective stimulus-position pairing and appears to be the major sensory driving force for reflex tear secretion by the lacrimal functional unit.

Heterosynaptic modulation of evoked synaptic potentials in layer II of the entorhinal cortex by activation of the parasubiculum

PubMed Central

Sparks, Daniel W.

2016-01-01

The superficial layers of the entorhinal cortex receive sensory and associational cortical inputs and provide the hippocampus with the majority of its cortical sensory input. The parasubiculum, which receives input from multiple hippocampal subfields, sends its single major output projection to layer II of the entorhinal cortex, suggesting that it may modulate processing of synaptic inputs to the entorhinal cortex. Indeed, stimulation of the parasubiculum can enhance entorhinal responses to synaptic input from the piriform cortex in vivo. Theta EEG activity contributes to spatial and mnemonic processes in this region, and the current study assessed how stimulation of the parasubiculum with either single pulses or short, five-pulse, theta-frequency trains may modulate synaptic responses in layer II entorhinal stellate neurons evoked by stimulation of layer I afferents in vitro. Parasubicular stimulation pulses or trains suppressed responses to layer I stimulation at intervals of 5 ms, and parasubicular stimulation trains facilitated layer I responses at a train-pulse interval of 25 ms. This suggests that firing of parasubicular neurons during theta activity may heterosynaptically enhance incoming sensory inputs to the entorhinal cortex. Bath application of the hyperpolarization-activated cation current (Ih) blocker ZD7288 enhanced the facilitation effect, suggesting that cholinergic inhibition of Ih may contribute. In addition, repetitive pairing of parasubicular trains and layer I stimulation induced a lasting depression of entorhinal responses to layer I stimulation. These findings provide evidence that theta activity in the parasubiculum may promote heterosynaptic modulation effects that may alter sensory processing in the entorhinal cortex. PMID:27146979

Stimulation artifact correction method for estimation of early cortico-cortical evoked potentials.

PubMed

Trebaul, Lena; Rudrauf, David; Job, Anne-Sophie; Mălîia, Mihai Dragos; Popa, Irina; Barborica, Andrei; Minotti, Lorella; Mîndruţă, Ioana; Kahane, Philippe; David, Olivier

2016-05-01

Effective connectivity can be explored using direct electrical stimulations in patients suffering from drug-resistant focal epilepsies and investigated with intracranial electrodes. Responses to brief electrical pulses mimic the physiological propagation of signals and manifest as cortico-cortical evoked potentials (CCEP). The first CCEP component is believed to reflect direct connectivity with the stimulated region but the stimulation artifact, a sharp deflection occurring during a few milliseconds, frequently contaminates it. In order to recover the characteristics of early CCEP responses, we developed an artifact correction method based on electrical modeling of the electrode-tissue interface. The biophysically motivated artifact templates are then regressed out of the recorded data as in any classical template-matching removal artifact methods. Our approach is able to make the distinction between the physiological responses time-locked to the stimulation pulses and the non-physiological component. We tested the correction on simulated CCEP data in order to quantify its efficiency for different stimulation and recording parameters. We demonstrated the efficiency of the new correction method on simulations of single trial recordings for early responses contaminated with the stimulation artifact. The results highlight the importance of sampling frequency for an accurate analysis of CCEP. We then applied the approach to experimental data. The model-based template removal was compared to a correction based on the subtraction of the averaged artifact. This new correction method of stimulation artifact will enable investigators to better analyze early CCEP components and infer direct effective connectivity in future CCEP studies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Electrically evoked compound action potentials recorded from the sheep spinal cord.

PubMed

Parker, John L; Karantonis, Dean M; Single, Peter S; Obradovic, Milan; Laird, James; Gorman, Robert B; Ladd, Leigh A; Cousins, Michael J

2013-01-01

The study aims to characterize the electrical response of dorsal column axons to depolarizing stimuli to help understand the mechanisms of spinal cord stimulation (SCS) for the relief of chronic pain. We recorded electrically evoked compound action potentials (ECAPs) during SCS in 10 anesthetized sheep using stimulating and recording electrodes on the same epidural SCS leads. A novel stimulating and recording system allowed artifact contamination of the ECAP to be minimized. The ECAP in the sheep spinal cord demonstrates a triphasic morphology, with P1, N1, and P2 peaks. The amplitude of the ECAP varies along the length of the spinal cord, with minimum amplitudes recorded from electrodes positioned over each intervertebral disc, and maximum amplitudes recorded in the midvertebral positions. This anatomically correlated depression of ECAP also correlates with the areas of the spinal cord with the highest thresholds for stimulation; thus regions of weakest response invariably had least sensitivity to stimulation by as much as a factor of two. The choice of stimulating electrode location can therefore have a profound effect on the power consumption for an implanted stimulator for SCS. There may be optimal positions for stimulation in the sheep, and this observation may translate to humans. Almost no change in conduction velocity (∼100 ms) was observed with increasing currents from threshold to twice threshold, despite increased Aβ fiber recruitment. Amplitude of sheep Aβ fiber potentials during SCS exhibit dependence on electrode location, highlighting potential optimization of Aβ recruitment and power consumption in SCS devices. © 2013 International Neuromodulation Society.

Transcranial electric motor evoked potential monitoring during spine surgery: is it safe?

PubMed

Schwartz, Daniel M; Sestokas, Anthony K; Dormans, John P; Vaccaro, Alexander R; Hilibrand, Alan S; Flynn, John M; Li, P Mark; Shah, Suken A; Welch, William; Drummond, Denis S; Albert, Todd J

2011-06-01

Retrospective review. To report on the safety of repetitive transcranial electric stimulation (RTES) for eliciting motor-evoked potentials during spine surgery. Theoretical concerns over the safety of RTES have hindered broader acceptance of transcranial electric motor-evoked potentials (tceMEP), despite successful implementation of spinal cord monitoring with tceMEPs in many large spine centers, as well as their apparent superiority over mixed-nerve somatosensory-evoked potentials (SSEP) for detection of spinal cord injury. The records of 18,862 consecutive patients who met inclusion criteria and underwent spine surgery with tceMEP monitoring were reviewed for RTES-related complications. This large retrospective review identified only 26 (0.14%) cases with RTES-related complications; all but one of these were tongue lacerations, most of which were self-limiting. The results demonstrate that RTES is a highly safe modality for monitoring spinal cord motor tract function intraoperatively.

Active Outer Hair Cells Affect the Sound-Evoked Vibration of the Reticular Lamina

NASA Astrophysics Data System (ADS)

Jacob, Stefan; Fridberger, Anders

2011-11-01

It is well established that the organ of Corti uses active mechanisms to enhance its sensitivity and frequency selectivity. Two possible mechanisms have been identified, both capable of producing mechanical forces, which can alter the sound-evoked vibration of the hearing organ. However, little is known about the effect of these forces on the sound-evoked vibration pattern of the reticular lamina. Current injections into scala media were used to alter the amplitude of the active mechanisms in the apex of the guinea pig temporal bone. We used time-resolved confocal imaging to access the vibration pattern of individual outer hair cells. During positive current injection the the sound-evoked vibration of outer hair cell row three increased while row one showed a small decrease. Negative currents reversed the observed effect. We conclude that the outer hair cell mediated modification of reticular lamina vibration patterns could contribute to the inner hair cell stimulation.

Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation.

PubMed

Normann, R A; Dowden, B R; Frankel, M A; Wilder, A M; Hiatt, S D; Ledbetter, N M; Warren, D A; Clark, G A

2012-04-01

The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation

NASA Astrophysics Data System (ADS)

Normann, R. A.; Dowden, B. R.; Frankel, M. A.; Wilder, A. M.; Hiatt, S. D.; Ledbetter, N. M.; Warren, D. A.; Clark, G. A.

2012-04-01

The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

Multicentre investigation on electrically evoked compound action potential and stapedius reflex: how do these objective measures relate to implant programming parameters?

PubMed

Van Den Abbeele, Thierry; Noël-Petroff, Nathalie; Akin, Istemihan; Caner, Gül; Olgun, Levent; Guiraud, Jeanne; Truy, Eric; Attias, Josef; Raveh, Eyal; Belgin, Erol; Sennaroglu, Gonca; Basta, Dietmar; Ernst, Arneborg; Martini, Alessandro; Rosignoli, Monica; Levi, Haya; Elidan, Joseph; Benghalem, Abdelhamid; Amstutz-Montadert, Isabelle; Lerosey, Yannick; De Vel, Eddy; Dhooge, Ingeborg; Hildesheimer, Minka; Kronenberg, Jona; Arnold, Laure

2012-02-01

The aims of this study were to collect data on electrically evoked compound action potential (eCAP) and electrically evoked stapedius reflex thresholds (eSRT) in HiResolution(TM) cochlear implant (CI) users, and to explore the relationships between these objective measures and behavioural measures of comfort levels (M-levels). A prospective study on newly implanted subjects was designed. The eCAP was measured intra-operatively and at first fitting through neural response imaging (NRI), using the SoundWave(TM) fitting software. The eSRT was measured intra-operatively by visual monitoring of the stapes, using both single-electrode stimulation and speech bursts (four electrodes stimulated at the same time). Measures of M-levels were performed according to standard clinical practice and collected at first fitting, 3 and 6 months of CI use. One hundred seventeen subjects from 14 centres, all implanted unilaterally with a HiResolution CII Bionic Ear(®) or HiRes 90K(®), were included in the study. Speech burst stimulation elicited a significantly higher eSRT success rate than single-electrode stimulation, 84 vs. 64% respectively. The NRI success rate was 81% intra-operatively, significantly increasing to 96% after 6 months. Fitting guidelines were defined on the basis of a single NRI measurement. Correlations, analysis of variance, and multiple regression analysis were applied to generate a predictive model for the M-levels. Useful insights were produced into the behaviour of objective measures according to time, electrode location, and fitting parameters. They may usefully assist in programming the CI when no reliable feedback is obtained through standard behavioural procedures.

Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

PubMed Central

Kozyrev, Vladislav; Eysel, Ulf T.; Jancke, Dirk

2014-01-01

Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. To circumvent these constraints, we performed optical imaging with voltage-sensitive dye (VSD) in an animal experimental setting using anaesthetized cats. The dye signals reflect gradual changes in the cells' membrane potential across several square millimeters of cortical tissue, thus enabling direct visualization of TMS-induced neuronal population dynamics. After application of a single TMS pulse across visual cortex, brief focal activation was immediately followed by synchronous suppression of a large pool of neurons. With consecutive magnetic pulses (10 Hz), widespread activity within this “basin of suppression” increased stepwise to suprathreshold levels and spontaneous activity was enhanced. Visual stimulation after repetitive TMS revealed long-term potentiation of evoked activity. Furthermore, loss of the “deceleration–acceleration” notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions. PMID:25187557

Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue.

PubMed

Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena; Tang, Qinggong; Chen, Yu; Erzurumlu, Reha S; Papkovsky, Dmitri B

2017-04-01

Brain imaging methods are continually improving. Imaging of the cerebral cortex is widely used in both animal experiments and charting human brain function in health and disease. Among the animal models, the rodent cerebral cortex has been widely used because of patterned neural representation of the whiskers on the snout and relative ease of activating cortical tissue with whisker stimulation. We tested a new planar solid-state oxygen sensor comprising a polymeric film with a phosphorescent oxygen-sensitive coating on the working side, to monitor dynamics of oxygen metabolism in the cerebral cortex following sensory stimulation. Sensory stimulation led to changes in oxygenation and deoxygenation processes of activated areas in the barrel cortex. We demonstrate the possibility of dynamic mapping of relative changes in oxygenation in live mouse brain tissue with such a sensor. Oxygenation-based functional magnetic resonance imaging (fMRI) is very effective method for functional brain mapping but have high costs and limited spatial resolution. Optical imaging of intrinsic signal (IOS) does not provide the required sensitivity, and voltage-sensitive dye optical imaging (VSDi) has limited applicability due to significant toxicity of the voltage-sensitive dye. Our planar solid-state oxygen sensor imaging approach circumvents these limitations, providing a simple optical contrast agent with low toxicity and rapid application. The planar solid-state oxygen sensor described here can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo. Further, this approach allows visualization of local neural activity with high temporal and spatial resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Kappa Opioid Receptors Mediate Heterosynaptic Suppression of Hippocampal Inputs in the Rat Ventral Striatum

PubMed Central

2017-01-01

Kappa opioid receptors (KORs) are highly enriched within the ventral striatum (VS) and are thought to modulate striatal neurotransmission. This includes presynaptic inhibition of local glutamatergic release from excitatory inputs to the VS. However, it is not known which inputs drive this modulation and what impact they have on the local circuit dynamics within the VS. Individual medium spiny neurons (MSNs) within the VS serve as a site of convergence for glutamatergic inputs arising from the PFC and limbic regions, such as the hippocampus (HP). Recent data suggest that competition can arise between these inputs with robust cortical activation leading to a reduction in ongoing HP-evoked MSN responses. Here, we investigated the contribution of KOR signaling in PFC-driven heterosynaptic suppression of HP inputs onto MSNs using whole-cell patch-clamp recordings in slices from adult rats. Optogenetically evoked HP EPSPs were greatly attenuated after a short latency (50 ms) following burst-like PFC electrical stimulation, and the magnitude of this suppression was partially reversed following blockade of GABAARs (GABA Type A receptors), but not GABABRs (GABA Type B receptors). A similar reduction in suppression was observed in the presence of the KOR antagonist, norBNI. Combined blockade of local GABAARs and KORs resulted in complete blockade of PFC-induced heterosynaptic suppression of less salient HP inputs. These findings highlight a mechanism by which strong, transient PFC activity can take precedence over other excitatory inputs to the VS. SIGNIFICANCE STATEMENT Emerging evidence suggests that kappa opioid receptor (KOR) activation can selectively modulate striatal glutamatergic inputs onto medium spiny neurons (MSNs). In this study, we found that robust cortical stimulation leads to a reduction in ongoing hippocampal-evoked MSNs responses through the combined recruitment of local inhibitory mechanisms and activation of presynaptic KORs in the ventral striatum (VS). These processes are likely to facilitate the efficient transfer of cortical information through the VS during critical decision making by dampening competing information from less salient excitatory inputs. These data provide a novel mechanism through which VS information processing could influence decision making, a function thought to occur primarily in the PFC. PMID:28642282

Responses evoked from man by acoustic stimulation

NASA Technical Reports Server (NTRS)

Galambos, R.; Hecox, K.; Picton, T.

1974-01-01

Clicks and other acoustic stimuli evoke time-locked responses from the brain of man. The properties of the waves recordable within the interval from 1 to 10 msec after the stimuli strike the eardrum are discussed along with factors influencing the waves in the 100 to 500 msec epoch. So-called brainstem responses from a normal young adult are considered. No waves were observed for clicks to weak to be heard. With increasing stimulus strength the waves become larger in amplitude and their latency shortens.

Correlation of the Hippocampal theta rhythm to changes in hypothalamic temperature

NASA Technical Reports Server (NTRS)

Saleh, M. A.; Horowitz, J. M.; Hsieh, A. C. L.

1974-01-01

Warming and cooling the preoptic anterior hypothalamic area in awake, loosely restrained rabbits was found to evoke theta rhythm. This is consistent with previous studies indicating that theta rhythm is a nonspecific response evoked by stimulation of several sensory modalities. Several studies have correlated theta rhythm with alertness. A neural pathway involving the hypothalamus, the hippocampus, the septal area, and the reticular formation is proposed. Thus, a role of this pathway may be to alert the animal to changes in its body temperature.

Source analysis of short and long latency vestibular-evoked potentials (VsEPs) produced by left vs. right ear air-conducted 500 Hz tone pips.

PubMed

Todd, N P M; Paillard, A C; Kluk, K; Whittle, E; Colebatch, J G

2014-06-01

Todd et al. (2014) have recently demonstrated the presence of vestibular dependent changes both in the morphology and in the intensity dependence of auditory evoked potentials (AEPs) when passing through the vestibular threshold as determined by vestibular evoked myogenic potentials (VEMPs). In this paper we extend this work by comparing left vs. right ear stimulation and by conducting a source analysis of the resulting evoked potentials of short and long latency. Ten healthy, right-handed subjects were recruited and evoked potentials were recorded to both left- and right-ear sound stimulation, above and below vestibular threshold. Below VEMP threshold, typical AEPs were recorded, consisting of mid-latency (MLR) waves Na and Pa followed by long latency AEPs (LAEPs) N1 and P2. In the supra-threshold condition, the expected changes in morphology were observed, consisting of: (1) short-latency vestibular evoked potentials (VsEPs) which have no auditory correlate, i.e. the ocular VEMP (OVEMP) and inion response related potentials; (2) a later deflection, labelled N42/P52, followed by the LAEPs N1 and P2. Statistical analysis of the vestibular dependent responses indicated a contralateral effect for inion related short-latency responses and a left-ear/right-hemisphere advantage for the long-latency responses. Source analysis indicated that the short-latency effects may be mediated by a contralateral projection to left cerebellum, while the long-latency effects were mediated by a contralateral projection to right cingulate cortex. In addition we found evidence of a possible vestibular contribution to the auditory T-complex in radial temporal lobe sources. These last results raise the possibility that acoustic activation of the otolith organs could potentially contribute to auditory processing. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.