Effects of theta burst stimulation on motor cortex excitability in Parkinson's disease.

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Zamir, Orit; Gunraj, Carolyn; Ni, Zhen; Mazzella, Filomena; Chen, Robert

2012-04-01

Long-term potentiation (LTP)-like plasticity induced by paired associative stimulation (PAS) is impaired in Parkinson's disease (PD). Intermittent theta burst stimulation (iTBS) is another rTMS protocol that produces LTP-like effects and increases cortical excitability but its effects are independent of afferent input. The aim of the present study was to examine the effects of iTBS on cortical excitability in PD. iTBS was applied to the motor cortex in 10 healthy subjects and 12 PD patients ON and OFF dopaminergic medications. Motor evoked potential (MEP) before and for 60 min after iTBS were used to examine the changes in cortical excitability induced by iTBS. Paired-pulse TMS was used to test whether intracortical circuits, including short interval intracortical inhibition, intracortical facilitation, short and long latency afferent inhibition, were modulated by iTBS. After iTBS, the control, PD ON and OFF groups had similar increases in MEP amplitude compared to baseline over the course of 60 min. Changes in intracortical circuits induced by iTBS were also similar for the different groups. iTBS produced similar effects on cortical excitability for PD patients and controls. Spike-timing dependent heterosynaptic LTP-like plasticity induced by PAS may be more impaired in PD than frequency dependent homosynaptic LTP-like plasticity induced by iTBS. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex.

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Goldsworthy, Mitchell R; Vallence, Ann-Maree; Hodyl, Nicolette A; Semmler, John G; Pitcher, Julia B; Ridding, Michael C

2016-01-01

To determine whether the intensity of transcranial magnetic stimulation (TMS) used to probe changes in corticospinal excitability influences the measured plasticity response to theta burst stimulation (TBS) of the human primary motor cortex. Motor evoked potential (MEP) input/output (I/O) curves were recorded before and following continuous TBS (cTBS) (Experiment 1; n=18) and intermittent TBS (iTBS) (Experiment 2; n=18). The magnitude and consistency of MEP depression induced by cTBS was greatest when probed using stimulus intensities at or above 150% of resting motor threshold (RMT). In contrast, facilitation of MEPs following iTBS was strongest and most consistent at 110% of RMT. The plasticity response to both cTBS and iTBS is influenced by the stimulus intensity used to probe the induced changes in corticospinal excitability. The results highlight the importance of the test stimulus intensity used to assess TBS-induced changes in corticospinal excitability when interpreting neuroplasticity data, and suggest that a number of test intensities may be required to reliably probe the plasticity response. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Quadri-Pulse Theta Burst Stimulation using Ultra-High Frequency Bursts - A New Protocol to Induce Changes in Cortico-Spinal Excitability in Human Motor Cortex

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Jung, Nikolai H; Gleich, Bernhard; Gattinger, Norbert

2016-01-01

Patterned transcranial magnetic stimulation (TMS) such as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS) can induce changes in cortico-spinal excitability, commonly referred to as long-term potentiation (LTP)-like and long-term depression (LTD)-like effects in human motor cortex (M...... of sinusoidal TMS pulses elicited either a posterior-anterior (PA) or anterior-posterior (AP) directed current in M1. Motor evoked potentials (MEPs) were recorded before and after qTBS to probe changes in cortico-spinal excitability. PA-qTBS at 666 Hz caused a decrease in PA-MEP amplitudes, whereas AP...... in cortico-spinal excitability. Induced current direction in the brain appears to be relevant when qTBS targets I-wave periodicity, corroborating that high-fidelity spike timing mechanisms are critical for inducing bi-directional plasticity in human M1....

Transient Beneficial Effects of Excitatory Theta Burst Stimulation in a Patient with Phonological Agraphia after Left Supramarginal Gyrus Infarction

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Nardone, Raffaele; De Blasi, Pierpaolo; Zuccoli, Giulio; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

2012-01-01

We report a patient showing isolated phonological agraphia after an ischemic stroke involving the left supramarginal gyrus (SMG). In this patient, we investigated the effects of focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the left SMG, corresponding to the Brodmann area (BA) 40. The patient…

Priming theta burst stimulation enhances motor cortex plasticity in young but not old adults.

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Opie, George M; Vosnakis, Eleni; Ridding, Michael C; Ziemann, Ulf; Semmler, John G

Primary motor cortex neuroplasticity is reduced in old adults, which may contribute to the motor deficits commonly observed in the elderly. Previous research in young subjects suggests that the neuroplastic response can be enhanced using non-invasive brain stimulation (NIBS), with a larger plastic response observed following priming with both long-term potentiation (LTP) and depression (LTD)-like protocols. However, it is not known if priming stimulation can also modulate plasticity in older adults. To investigate if priming NIBS can be used to modulate motor cortical plasticity in old subjects. In 16 young (22.3 ± 1.0 years) and 16 old (70.2 ± 1.7 years) subjects, we investigated the response to intermittent theta burst stimulation (iTBS; LTP-like) when applied 10 min after sham stimulation, continuous TBS (cTBS; LTD-like) or an identical block of iTBS. Corticospinal plasticity was assessed by recording changes in motor evoked potential (MEP) amplitude. In young subjects, priming with cTBS (cTBS + iTBS) resulted in larger MEPs than priming with either iTBS (iTBS + iTBS; P = 0.001) or sham (sham + iTBS; P iTBS + iTBS than sham + iTBS (P iTBS + iTBS was not different to sham + iTBS (P > 0.9), whereas the response to cTBS + iTBS was reduced relative to iTBS + iTBS (P = 0.02) and sham + iTBS (P = 0.04). Priming TBS is ineffective for modifying M1 plasticity in older adults, which may limit the therapeutic use of priming stimulation in neurological conditions common in the elderly. Copyright © 2017 Elsevier Inc. All rights reserved.

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study

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Caio Abujadi

2017-12-01

Full Text Available Objective: Theta-burst stimulation (TBS modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD. At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Methods: Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Results: Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. Conclusion: These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study.

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Abujadi, Caio; Croarkin, Paul E; Bellini, Bianca B; Brentani, Helena; Marcolin, Marco A

2017-12-11

Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

Inter- and Intra-individual variability following intermittent theta burst stimulation: implications for rehabilitation and recovery.

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Hinder, Mark R; Goss, Emily L; Fujiyama, Hakuei; Canty, Alison J; Garry, Michael I; Rodger, Jennifer; Summers, Jeffery J

2014-01-01

The continued refinement of non-invasive brain stimulation (NBS) techniques is indicative of promising clinical and rehabilitative interventions that are able to modulate cortical excitability. Intermittent theta burst stimulation (iTBS) is one such technique that can increase cortical excitability, purportedly via LTP-like mechanisms. While iTBS may have the capacity to promote recovery after neurological injury, and to combat cognitive and motor decline, recent reports observed highly variable effects across individuals, questioning the efficacy of iTBS as a clinical tool. The aim of this study was to examine intra-individual reliability and inter-individual variability in responses to iTBS. Thirty healthy participants completed two experimental sessions of the iTBS protocol 1-3 weeks apart. Motor evoked potentials in response to single pulse TMS were used to assess corticospinal excitability prior to, and up to 36 min following, iTBS. At the group level, iTBS evoked statistically significant increases in motor cortical excitability across both sessions (P iTBS is capable of inducing relatively robust and consistent effects within and between young individuals. As such, the capacity for iTBS to be exploited in clinical and rehabilitative interventions should continue to be explored. Copyright © 2014 Elsevier Inc. All rights reserved.

Remote effects of intermittent theta burst stimulation of the human pharyngeal motor system.

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Mistry, Satish; Michou, Emilia; Rothwell, John; Hamdy, Shaheen

2012-08-01

Intermittent theta burst stimulation (iTBS) is a novel, non-invasive form of brain stimulation capable of facilitating excitability of the human primary motor cortex with therapeutic potential in the treatment of neurological conditions, such as multiple sclerosis. The objectives of this study were to evaluate the effects of iTBS on cortical properties in the human pharyngeal motor system. Transcranial magnetic stimulation (TMS)-evoked pharyngeal motor responses were recorded via a swallowed intra-luminal catheter and used to assess motor cortical pathways to the pharynx in both hemispheres before and for up to 90 min after iTBS in 15 healthy adults (nine male/six female, 22-59 years old). Active/sham iTBS comprised 600 intermittent repetitive TMS pulses, delivered in a double-blind pseudo-randomised order over each hemisphere on separate days at least 1 week apart. Abductor pollicis brevis (APB) recordings were used as control. Hemispheric interventional data were compared with sham using repeated-measures anova. iTBS was delivered at an average intensity of 43±1% of stimulator output. Compared with sham, iTBS to the hemisphere with stronger pharyngeal projections induced increased responses only in the contralateral weaker projection 60-90 min post-iTBS (maximum 54±19%, P≤0.007), with no change in stronger hemisphere responses. By contrast, iTBS to weaker projections had no significant effects (P=0.39) on either hemisphere. APB responses similarly did not change significantly (P=0.78) across all study arms. We conclude that iTBS can induce remote changes in corticobulbar excitability. While further studies will clarify the extent of these changes, iTBS holds promise as a potential treatment for dysphagia after unilateral brain damage. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Boosting the LTP-like plasticity effect of intermittent theta-burst stimulation using gamma transcranial alternating current stimulation.

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Guerra, Andrea; Suppa, Antonio; Bologna, Matteo; D'Onofrio, Valentina; Bianchini, Edoardo; Brown, Peter; Di Lazzaro, Vincenzo; Berardelli, Alfredo

2018-03-24

Transcranial Alternating Current Stimulation (tACS) consists in delivering electric current to the brain using an oscillatory pattern that may entrain the rhythmic activity of cortical neurons. When delivered at gamma frequency, tACS modulates motor performance and GABA-A-ergic interneuron activity. Since interneuronal discharges play a crucial role in brain plasticity phenomena, here we co-stimulated the primary motor cortex (M1) in healthy subjects by means of tACS during intermittent theta-burst stimulation (iTBS), a transcranial magnetic stimulation paradigm known to induce long-term potentiation (LTP)-like plasticity. We measured and compared motor evoked potentials before and after gamma, beta and sham tACS-iTBS. While we delivered gamma-tACS, we also measured short-interval intracortical inhibition (SICI) to detect any changes in GABA-A-ergic neurotransmission. Gamma, but not beta and sham tACS, significantly boosted and prolonged the iTBS-induced after-effects. Interestingly, the extent of the gamma tACS-iTBS after-effects correlated directly with SICI changes. Overall, our findings point to a link between gamma oscillations, interneuronal GABA-A-ergic activity and LTP-like plasticity in the human M1. Gamma tACS-iTBS co-stimulation might represent a new strategy to enhance and prolong responses to plasticity-inducing protocols, thereby lending itself to future applications in the neurorehabilitation setting. Copyright © 2018 Elsevier Inc. All rights reserved.

Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition.

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Obeso, Ignacio; Wilkinson, Leonora; Teo, James T; Talelli, Penelope; Rothwell, John C; Jahanshahi, Marjan

Stopping an ongoing motor response or resolving conflict induced by conflicting stimuli are associated with activation of a right-lateralized network of inferior frontal gyrus (IFG), pre-supplementary motor area (pre-SMA) and subthalamic nucleus (STN). However, the roles of the right IFG and pre-SMA in stopping a movement and in conflict resolution remain unclear. We used continuous theta burst stimulation (cTBS) to examine the involvement of the right IFG and pre-SMA in inhibition and conflict resolution using the conditional stop signal task. We measured stop signal reaction time (SSRT, measure of reactive inhibition), response delay effect (RDE, measure of proactive action restraint) and conflict induced slowing (CIS, measure of conflict resolution). Stimulation over the pre-SMA resulted in significantly shorter SSRTs (improved inhibition) compared to sham cTBS. This effect was not observed for CIS, RDE, or any other measures. cTBS over the right IFG had no effect on SSRT, CIS, RDE or on any other measure. The improvement of SSRT with cTBS over the pre-SMA suggests its critical contribution to stopping ongoing movements. Copyright © 2017 Elsevier Inc. All rights reserved.

The facilitatory effects of intermittent theta burst stimulation on corticospinal excitability are enhanced by nicotine.

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Swayne, Orlando B C; Teo, James T H; Greenwood, Richard J; Rothwell, John C

2009-08-01

Intermittent theta burst stimulation (iTBS) is increasingly widely used as a means of facilitating corticospinal excitability in the human primary motor cortex. This form of facilitatory plasticity within the stimulated cortex may occur by induction of long term potentiation (LTP). In animal models, agonists of nicotinic acetylcholine receptors have been shown to modulate or induce LTP; we thus sought to test whether nicotine may modulate the effects of iTBS on corticospinal excitability in humans. A double-blind placebo-controlled cross-over design study was conducted with 10 healthy subjects. iTBS was delivered 60min after subjects took either 4mg nicotine or placebo lozenges, and motor-evoked potentials (MEPs) were then recorded for 40min after the end of stimulation. In the placebo arm, iTBS produced an increase in the amplitudes of MEPs which lasted for 5min. In the nicotine arm, iTBS produced a more pronounced facilitation of MEPs that was still present at 40min. In a control experiment, nicotine alone had no effect on MEP amplitudes when given in the absence of iTBS. These data indicate that the effects of iTBS can be enhanced and prolonged by nicotine. These results are consistent with animal models demonstrating nicotinic modulation of facilitatory plasticity, and will be of interest to investigators seeking to enhance artificially induced changes in cortical excitability.

Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia

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Joseph C. Griffis

2016-01-01

Full Text Available The effects of noninvasive neurostimulation on brain structure and function in chronic poststroke aphasia are poorly understood. We investigated the effects of intermittent theta burst stimulation (iTBS applied to residual language-responsive cortex in chronic patients using functional and anatomical MRI data acquired before and after iTBS. Lateralization index (LI analyses, along with comparisons of inferior frontal gyrus (IFG activation and connectivity during covert verb generation, were used to assess changes in cortical language function. Voxel-based morphometry (VBM was used to assess effects on regional grey matter (GM. LI analyses revealed a leftward shift in IFG activity after treatment. While left IFG activation increased, right IFG activation decreased. Changes in right to left IFG connectivity during covert verb generation also decreased after iTBS. Behavioral correlations revealed a negative relationship between changes in right IFG activation and improvements in fluency. While anatomical analyses did not reveal statistically significant changes in grey matter volume, the fMRI results provide evidence for changes in right and left IFG function after iTBS. The negative relationship between post-iTBS changes in right IFG activity during covert verb generation and improvements in fluency suggests that iTBS applied to residual left-hemispheric language areas may reduce contralateral responses related to language production and facilitate recruitment of residual language areas after stroke.

Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia.

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Griffis, Joseph C; Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

2016-01-01

The effects of noninvasive neurostimulation on brain structure and function in chronic poststroke aphasia are poorly understood. We investigated the effects of intermittent theta burst stimulation (iTBS) applied to residual language-responsive cortex in chronic patients using functional and anatomical MRI data acquired before and after iTBS. Lateralization index (LI) analyses, along with comparisons of inferior frontal gyrus (IFG) activation and connectivity during covert verb generation, were used to assess changes in cortical language function. Voxel-based morphometry (VBM) was used to assess effects on regional grey matter (GM). LI analyses revealed a leftward shift in IFG activity after treatment. While left IFG activation increased, right IFG activation decreased. Changes in right to left IFG connectivity during covert verb generation also decreased after iTBS. Behavioral correlations revealed a negative relationship between changes in right IFG activation and improvements in fluency. While anatomical analyses did not reveal statistically significant changes in grey matter volume, the fMRI results provide evidence for changes in right and left IFG function after iTBS. The negative relationship between post-iTBS changes in right IFG activity during covert verb generation and improvements in fluency suggests that iTBS applied to residual left-hemispheric language areas may reduce contralateral responses related to language production and facilitate recruitment of residual language areas after stroke.

Differential impact of continuous theta-burst stimulation over left and right DLPFC on planning.

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Kaller, Christoph P; Heinze, Katharina; Frenkel, Annekathrein; Läppchen, Claus H; Unterrainer, Josef M; Weiller, Cornelius; Lange, Rüdiger; Rahm, Benjamin

2013-01-01

Most neuroimaging studies on planning report bilateral activations of the dorsolateral prefrontal cortex (dlPFC). Recently, these concurrent activations of left and right dlPFC have been shown to double dissociate with different cognitive demands imposed by the planning task: Higher demands on the extraction of task-relevant information led to stronger activation in left dlPFC, whereas higher demands on the integration of interdependent information into a coherent action sequence entailed stronger activation of right dlPFC. Here, we used continuous theta-burst stimulation (cTBS) to investigate the supposed causal structure-function mapping underlying this double dissociation. Two groups of healthy subjects (left-lateralized stimulation, n = 26; right-lateralized stimulation, n = 26) were tested within-subject on a variant of the Tower of London task following either real cTBS over dlPFC or sham stimulation over posterior parietal cortex. Results revealed that, irrespective of specific task demands, cTBS over left and right dlPFC was associated with a global decrease and increase, respectively, in initial planning times compared to sham stimulation. Moreover, no interaction between task demands and stimulation type (real vs. sham) and/or stimulation side (left vs. right hemisphere) were found. Together, against expectations from previous neuroimaging data, lateralized cTBS did not lead to planning-parameter specific changes in performance, but instead revealed a global asymmetric pattern of faster versus slower task processing after left versus right cTBS. This global asymmetry in the absence of any task-parameter specific impact of cTBS suggests that different levels of information processing may span colocalized, but independent axes of functional lateralization in the dlPFC. Copyright © 2011 Wiley Periodicals, Inc.

Enhancement of motor learning by focal intermittent theta burst stimulation (iTBS) of either the primary motor (M1) or somatosensory area (S1) in healthy human subjects.

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Platz, Thomas; Adler-Wiebe, Marija; Roschka, Sybille; Lotze, Martin

2018-01-01

Motor rehabilitation after brain damage relies on motor re-learning as induced by specific training. Non-invasive brain stimulation (NIBS) can alter cortical excitability and thereby has a potential to enhance subsequent training-induced learning. Knowledge about any priming effects of NIBS on motor learning in healthy subjects can help to design targeted therapeutic applications in brain-damaged subjects. To examine whether complex motor learning in healthy subjects can be enhanced by intermittent theta burst stimulation (iTBS) to primary motor or sensory cortical areas. Eighteen young healthy subjects trained eight different arm motor tasks (arm ability training, AAT) once a day for 5 days using their left non-dominant arm. Except for day 1 (baseline), training was performed after applying an excitatory form of repetitive transcranial magnetic stimulation (iTBS) to either (I) right M1 or (II) S1, or (III) sham stimulation to the right M1. Subjects were randomly assigned to conditions I, II, or III. A principal component analysis of the motor behaviour data suggested eight independent motor abilities corresponding to the 8 trained tasks. AAT induced substantial motor learning across abilities with generalisation to a non-trained test of finger dexterity (Nine-Hole-Peg-Test, NHPT). Participants receiving iTBS (to either M1 or S1) showed better performance with the AAT tasks over the period of training compared to sham stimulation as well as a bigger improvement with the generalisation task (NHPT) for the trained left hand after training completion. Priming with an excitatory repetitive transcranial magnetic stimulation as iTBS of either M1 or S1 can enhance motor learning across different sensorimotor abilities.

Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

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Daina S. E. Dickins

2015-01-01

Full Text Available Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years underwent intermittent theta burst stimulation (iTBS whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS.

Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

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Dickins, Daina S. E.; Sale, Martin V.

2015-01-01

Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS. PMID:26064691

Efficacy and safety of bilateral continuous theta burst stimulation (cTBS for the treatment of chronic tinnitus: design of a three-armed randomized controlled trial

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Plontke Stefan K

2009-08-01

Full Text Available Abstract Background Tinnitus, the perception of sound and noise in absence of an auditory stimulus, has been shown to be associated with maladaptive neuronal reorganization and increased activity of the temporoparietal cortex. Transient modulation of tinnitus by repetitive transcranial magnetic stimulation (rTMS indicated that these areas are critically involved in the pathophysiology of tinnitus and suggested new treatment strategies. However, the therapeutic efficacy of rTMS in tinnitus is still unclear, individual response is variable, and the optimal stimulation area disputable. Recently, continuous theta burst stimulation (cTBS has been put forward as an effective rTMS protocol for the reduction of pathologically enhanced cortical excitability. Methods 48 patients with chronic subjective tinnitus will be included in this randomized, placebo controlled, three-arm trial. The treatment consists of two trains of cTBS applied bilaterally to the secondary auditory cortex, the temporoparietal associaction cortex, or to the lower occiput (sham condition every working day for four weeks. Primary outcome measure is the change of tinnitus distress as quantified by the Tinnitus Questionnaire (TQ. Secondary outcome measures are tinnitus loudness and annoyance as well as tinnitus change during and after treatment. Audiologic and speech audiometric measurements will be performed to assess potential side effects. The aim of the present trail is to investigate effectiveness and safety of a four weeks cTBS treatment on chronic tinnitus and to compare two areas of stimulation. The results will contribute to clarify the therapeutic capacity of rTMS in tinnitus. Trial registration The trial was registered with the clinical trials register of http://www.clinicaltrials.gov (NCT00518024.

Intermittent Theta Burst Stimulation Increases Reward Responsiveness in Individuals with Higher Hedonic Capacity.

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Duprat, Romain; De Raedt, Rudi; Wu, Guo-Rong; Baeken, Chris

2016-01-01

Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (DLPFC) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing. However, the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be elucidated. In this sham-controlled study in healthy individuals, we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation (iTBS) on reward responsiveness, as well as the influence of trait hedonic capacity. We used a randomized crossover single session iTBS design with an interval of 1 week. We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity (the ability to experience pleasure) with the temporal experience of pleasure scale questionnaire. As expected, the participants developed a response bias toward the most rewarded stimulus (rich stimulus). Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus (lean stimulus). Active or sham stimulation did not seem to influence the outcome. However, when taking into account individual trait hedonic capacity, we found an early significant increase in the response bias only after active iTBS. The higher the individual's trait hedonic capacity, the more the response bias toward the rich stimulus increased after the active stimulation. When taking into account trait hedonic capacity, one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity. This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system.

Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion

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Kathrin eHoppenrath

2016-03-01

Full Text Available Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV fast-spiking interneurons (FSIs, evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs of FSIs start to grow around postnatal day 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo – in vitro whole-cell patch clamp recordings from pre-labelled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28 and older animals (PD40-62. Slices of verum iTBS-treated rats further showed higher rates of spontaneous EPSCs. Based on these and previous findings we conclude that FSIs are particularly sensitive to theta-burst stimulation during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

Facilitation of speech repetition accuracy by theta burst stimulation of the left posterior inferior frontal gyrus.

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Restle, Julia; Murakami, Takenobu; Ziemann, Ulf

2012-07-01

The posterior part of the inferior frontal gyrus (pIFG) in the left hemisphere is thought to form part of the putative human mirror neuron system and is assigned a key role in mapping sensory perception onto motor action. Accordingly, the pIFG is involved in motor imitation of the observed actions of others but it is not known to what extent speech repetition of auditory-presented sentences is also a function of the pIFG. Here we applied fMRI-guided facilitating intermittent theta burst transcranial magnetic stimulation (iTBS), or depressant continuous TBS (cTBS), or intermediate TBS (imTBS) over the left pIFG of healthy subjects and compared speech repetition accuracy of foreign Japanese sentences before and after TBS. We found that repetition accuracy improved after iTBS and, to a lesser extent, after imTBS, but remained unchanged after cTBS. In a control experiment, iTBS was applied over the left middle occipital gyrus (MOG), a region not involved in sensorimotor processing of auditory-presented speech. Repetition accuracy remained unchanged after iTBS of MOG. We argue that the stimulation type and stimulation site specific facilitating effect of iTBS over left pIFG on speech repetition accuracy indicates a causal role of the human left-hemispheric pIFG in the translation of phonological perception to motor articulatory output for repetition of speech. This effect may prove useful in rehabilitation strategies that combine repetitive speech training with iTBS of the left pIFG in speech disorders, such as aphasia after cerebral stroke. Copyright © 2012 Elsevier Ltd. All rights reserved.

Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition.

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Allanah Harrington

Full Text Available Theta burst stimulation (TBS of the cerebellum, a potential therapy for neurological disease, can modulate corticospinal excitability via the dentato-thalamo-cortical pathway, but it is uncertain whether its effects are mediated via inhibitory or facilitatory networks. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on the N100 waveform of the TMS-evoked potential (TEP, a marker of intracortical GABAB-mediated inhibition. 16 healthy participants (aged 18-30 years; 13 right handed and 3 left handed received 30Hz intermittent TBS (iTBS, continuous TBS (cTBS or sham stimulation over the right cerebellum, in three separate sessions. The first 8 participants received TBS at a stimulus intensity of 80% of active motor threshold (AMT, while the remainder received 90% of AMT. Motor evoked potentials (MEP and TEP were recorded before and after each treatment, by stimulating the first dorsal interosseus area of the left motor cortex. Analysis of the 13 right handed participants showed that iTBS at 90% of AMT increased the N100 amplitude compared to sham and cTBS, without significantly altering MEP amplitude. cTBS at 80% of active motor threshold decreased the N100 amplitude and cTBS overall reduced resting MEP amplitude. The study demonstrates effects of 30Hz cerebellar TBS on inhibitory cortical networks that may be useful for treatment of neurological conditions associated with dysfunctional intracortical inhibition.

Accelerated intermittent Theta Burst stimulation for suicide risk in therapy-resistant depressed patients: a randomized, sham-controlled trial.

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Stefanie Desmyter

2016-09-01

Full Text Available Objectives We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex in a randomized, sham-controlled cross-over design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI. Results The iTBS protocol was safe and well-tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016. The decrease in suicide risk lasted up to one month after baseline, even in depression non-responders. Conclusions This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary.(clinicaltrials.gov identifier: NCT01832805

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial.

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Desmyter, Stefanie; Duprat, Romain; Baeken, Chris; Van Autreve, Sara; Audenaert, Kurt; van Heeringen, Kees

2016-01-01

Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI). Results: The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016). The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders. Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805).

Network based statistical analysis detects changes induced by continuous theta burst stimulation on brain activity at rest.

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Chiara eMastropasqua

2014-08-01

Full Text Available We combined continuous theta burst stimulation (cTBS and resting state (RS -fMRI approaches to investigate changes in functional connectivity (FC induced by right dorso-lateral prefrontal cortex (DLPFC cTBS at rest in a group of healthy subjects. Seed based fMRI analysis revealed a specific pattern of correlation between the right prefrontal cortex and several brain regions: based on these results, we defined a 29-node network to assess changes in each network connection before and after, respectively, DLPFC-cTBS and sham sessions. A decrease of correlation between the right prefrontal cortex and right parietal cortex (Brodmann areas 46 and 40 respectively was detected after cTBS, while no significant result was found when analyzing sham-session data. To our knowledge, this is the first study that demonstrates within-subject changes in FC induced by cTBS applied on prefrontal area. The possibility to induce selective changes in a specific region without interfering with functionally correlated area could have several implications for the study of functional properties of the brain, and for the emerging therapeutic strategies based on transcranial stimulation.

Agonist contraction during intermittent theta burst stimulation enhances motor cortical plasticity of the wrist flexors.

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Mirdamadi, J L; Suzuki, L Y; Meehan, S K

2015-03-30

Differences in cortical control across the different muscles of the upper limb may mitigate the efficacy of TMS interventions targeting a specific muscle. The current study sought to determine whether weak concurrent contraction during TMS could enhance the efficacy of intermittent theta burst stimulation (iTBS) in the forearm flexors. Motor evoked potentials (MEP) were elicited from the flexor (FCR) and extensor carpi radialis (ECR) motor cortical hotspots before and after iTBS over the FCR cortical hotspot. During iTBS the FCR was either relaxed (iTBS-Relax) or tonically contracted to 10% of maximum voluntary force (iTBS-Contract). iTBS-Relax failed to produce consistent potentiation of MEPFCR amplitude. Individuals with a relatively lower RMTFCR compared RMTECR demonstrated MEPFCR facilitation post-iTBS-Relax. Individuals with relatively higher RMTFCR demonstrated less facilitation and even suppression of MEPFCR amplitude. iTBS-Contract facilitated MEPFCR amplitude but only for MEPFCR evoked from the ECR hotspot. Interactions between overlapping cortical representations determine the efficacy of iTBS. Tonic contraction increases the efficacy of iTBS by enhancing the volume of the cortical representation. However, metaplastic effects may attenuate the enhancement of MEP gain at the motor cortical hotspot. The use of TMS as an adjunct to physical therapy should account for inter-muscle interactions when targeting muscles of the forearm. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effect of single and repeated prefrontal intermittent theta burst stimulation on cortical reactivity and working memory.

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Chung, Sung Wook; Rogasch, Nigel C; Hoy, Kate E; Fitzgerald, Paul B

With an increasing interest in the use of theta burst stimulation (TBS) as a cognitive enhancer and a potential therapeutic tool for psychiatric disorders, there is a need to identify optimal parameters of TBS in the prefrontal cortex. This study examined the effect of two blocks of prefrontal intermittent TBS (iTBS) on cortical reactivity and working memory performance, compared to one block of iTBS and sham stimulation. We hypothesized that greater cortical effects would be obtained with two blocks of iTBS. Eighteen healthy participants attended three experimental sessions and received either sham, one block or two blocks of iTBS with a 15-min interval. Concurrent transcranial magnetic stimulation with electroencephalography (TMS-EEG) was used to assess the change in cortical reactivity via TMS-evoked potentials. Working memory performance was assessed using the N-back task. Cluster-based permutation statistics and two-way ANOVAs were used for neurophysiological and behavioural data, respectively. Both single and two blocks of iTBS resulted in a significant increase in the amplitude of TMS-evoked N100 and P200. No significant differences were observed between active conditions in either neurophysiological changes or working memory performance, and both failed to improve working memory performance relative to sham. Two blocks of iTBS did not result in stronger measured effects as compared to one block of iTBS. Future studies are needed to identify the optimal stimulation pattern in order to achieve a desired effect. It is also important to establish the best approach in quantifying neuromodulatory effects targeting the prefrontal cortex. Copyright © 2018 Elsevier Inc. All rights reserved.

Continuous theta burst demonstrates a causal role of premotor homunculus in action interpretation

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Michael, John Andrew

2014-01-01

Although it is well established that regions of premotor cortex (PMC) are active during action observation, it remains controversial whether they play a causal role in action understanding. In the experiment reported here, we used off-line continuous theta-burst stimulation (cTBS) to investigate ...

Transcranial Magnetic Stimulation with Intermittent Theta Burst Stimulation Alters Corticospinal Output in Patients with Chronic Incomplete Spinal Cord Injury

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Hunter J. Fassett

2017-08-01

Full Text Available Intermittent theta burst stimulation (iTBS is intended primarily to alter corticospinal excitability, creating an attractive opportunity to alter neural output following incomplete spinal cord injury (SCI. This study is the first to assess the effects of iTBS in SCI. Eight individuals with chronic incomplete SCI were studied. Sham or real iTBS was delivered (to each participant over primary motor and somatosensory cortices in separate sessions. Motor-evoked potential (MEP recruitment curves were obtained from the flexor carpi radialis muscle before and after iTBS. Results indicate similar responses for iTBS to both motor and somatosensory cortex and reduced MEPs in 56.25% and increased MEPs in 25% of instances. Sham stimulation exceeded real iTBS effects in the remaining 18.25%. It is our opinion that observing short-term neuroplasticity in corticospinal output in chronic SCI is an important advance and should be tested in future studies as an opportunity to improve function in this population. We emphasize the need to re-consider the importance of the direction of MEP change following a single session of iTBS since the relationship between MEP direction and motor function is unknown and multiple sessions of iTBS may yield very different directional results. Furthermore, we highlight the importance of including sham control in the experimental design. The fundamental point from this pilot research is that a single session of iTBS is often capable of creating short-term change in SCI. Future sham-controlled randomized trials may consider repeat iTBS sessions to promote long-term changes in corticospinal excitability.

Enhanced motor skill acquisition in the non-dominant upper extremity using intermittent theta burst stimulation and transcranial direct current stimulation.

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Butts, Raymond J; Kolar, Melissa B; Newman-Norlund, Roger D

2014-01-01

Individuals suffering from motor impairments often require physical therapy (PT) to help improve their level of function. Previous investigations suggest that both intermittent theta burst stimulation (iTBS) and bihemispheric transcranial direct current stimulation (tDCS) may increase the speed and extent of motor learning/relearning. The purpose of the current study was to explore the feasibility and effectiveness of a novel, non-invasive brain stimulation approach that combined an iTBS primer, and bihemispheric stimulation coupled with motor training. We hypothesized that individuals exposed to this novel treatment would make greater functional improvements than individuals undergoing sham stimulation when tested immediately following, 24-h, and 7-days post-training. A total of 26 right-handed, healthy young adults were randomly assigned to either a treatment (n = 15) or control group (n = 12). iTBS (20 trains of 10 pulse triplets each delivered at 80% active motor threshold (AMT) / 50 Hz over 191.84 s) and bihemispheric tDCS (1.0 ma for 20 min) were used as a primer to, and in conjunction with, 20 min of motor training, respectively. Our primary outcome measure was performance on the Jebsen-Taylor Hand Function (JTHF) test. Participants tolerated the combined iTBS/bihemispheric stimulation treatment without complaint. While performance gains in the sham and stimulation group were not significant immediately after training, they were nearly significant 24-h post training (p = 0.055), and were significant at 7-days post training (p iTBS/bihemispheric stimulation protocol is both feasible and effective. Future research should examine the mechanistic explanation of this approach as well as the potential of using this approach in clinical populations.

Does a single session of theta-burst transcranial magnetic stimulation of inferior temporal cortex affect tinnitus perception?

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Moser Tobias

2009-05-01

Full Text Available Abstract Background Cortical excitability changes as well as imbalances in excitatory and inhibitory circuits play a distinct pathophysiological role in chronic tinnitus. Repetitive transcranial magnetic stimulation (rTMS over the temporoparietal cortex was recently introduced to modulate tinnitus perception. In the current study, the effect of theta-burst stimulation (TBS, a novel rTMS paradigm was investigated in chronic tinnitus. Twenty patients with chronic tinnitus completed the study. Tinnitus severity and loudness were monitored using a tinnitus questionnaire (TQ and a visual analogue scale (VAS before each session. Patients received 600 pulses of continuous TBS (cTBS, intermittent TBS (iTBS and intermediate TBS (imTBS over left inferior temporal cortex with an intensity of 80% of the individual active or resting motor threshold. Changes in subjective tinnitus perception were measured with a numerical rating scale (NRS. Results TBS applied to inferior temporal cortex appeared to be safe. Although half of the patients reported a slight attenuation of tinnitus perception, group analysis resulted in no significant difference when comparing the three specific types of TBS. Converting the NRS into the VAS allowed us to compare the time-course of aftereffects. Only cTBS resulted in a significant short-lasting improvement of the symptoms. In addition there was no significant difference when comparing the responder and non-responder groups regarding their anamnestic and audiological data. The TQ score correlated significantly with the VAS, lower loudness indicating less tinnitus distress. Conclusion TBS does not offer a promising outcome for patients with tinnitus in the presented study.

Enhanced Motor Skill Acquisition in the Non-dominant Upper Extremity using Intermittent Theta Burst Stimulation and Transcranial Direct Current Stimulation

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Ray eButts

2014-06-01

Full Text Available Individuals suffering from motor impairments often require physical therapy (PT to help improve their level of function. Previous investigations suggest that both intermittent theta burst stimulation (iTBS and bihemispheric transcranial direct current stimulation may increase the speed and extent of motor learning/relearning and that this increase may be related to brain derived neurotrophic factor (BDNF. The purpose of the current study was to explore the feasibility and effectiveness of a novel, non-invasive brain stimulation approach that combined an iTBS primer, and bihemispheric stimulation coupled with motor training. We hypothesized that individuals exposed to this novel treatment would make greater functional improvements than individuals undergoing sham stimulation when tested immediately following, 24-hours, and 7-days post-training. A total of 26 right-handed, healthy young adults were randomly assigned to either a treatment (n = 15 or control group (n = 12. iTBS (20 trains of 10 pulse triplets each delivered at 80% AMT / 50Hz over 191.84 seconds and bihemispheric tDCS (1.0 ma for 20 minutes were used as a primer to, and in conjunction with, 20 minutes of motor training, respectively. Our primary outcome measure was performance on the Jebsen-Taylor Hand Function Test. Participants tolerated the combined iTBS/bihemispheric stimulation treatment without complaint. While performance gains in the sham and stimulation group were not significant immediately after training, they were nearly significant 24-hours post training (p = 0.055, and were significant at 7-days post training (p < 0.05. These results suggest that the combined iTBS/bihemispheric stimulation protocol is both feasible and effective. Future research should examine the mechanistic explanation of this approach as well as the potential of using this approach in clinical populations.

The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex.

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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

Effects of intermittent theta burst stimulation on cerebral blood flow and cerebral vasomotor reactivity.

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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

Effect of 30 Hz Theta Burst Transcranial Magnetic Stimulation on the Primary Motor Cortex in Children and Adolescents

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Ernest ePedapati

2015-02-01

Full Text Available Fourteen healthy children (13.8±2.2 years, range 10 to 16; M:F=5:9 received 30 Hz intermittent theta burst transcranial magnetic stimulation (iTBS with a stimulation intensity of 70% of resting motor threshold (RMT with a total of 300 (iTBS300 pulses. All volunteers were free of neurologic, psychiatric and serious medical illnesses, not taking any neuropsychiatric medications, and did not have any contraindications to Transcranial Magnetic Stimulation. Changes in the mean amplitudes of motor-evoked potentials from baseline following iTBS were expressed as a ratio and assessed from 1 to 10 minutes (BLOCK1 and 1 to 30 minutes (BLOCK2 using repeated-measures analysis of variance. All 14 subjects completed iTBS300 over the dominant primary motor cortex (M1 without any clinically reported adverse events. ITBS300 produced significant M1 facilitation (F5,65=3.165, p=0.01 at BLOCK1 and trend level M1 facilitation at BLOCK2 (F10,129=1.69, p=0.089. Although iTBS300 (stimulation duration of 92 seconds at 70% RMT delivered over M1 in typically developed children was well-tolerated and produced on average significant facilitatory changes in cortical excitability, the post-iTBS300 neurophysiologic response was variable in our small sample. ITBS300-induced changes may represent a potential neuroplastic biomarker in healthy children and those with neuro-genetic or neuro-psychiatric disorders. However, a larger sample size is needed to address safety and concerns of response variability.

Effect of 30 Hz theta burst transcranial magnetic stimulation on the primary motor cortex in children and adolescents

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Pedapati, Ernest V.; Gilbert, Donald L.; Horn, Paul S.; Huddleston, David A.; Laue, Cameron S.; Shahana, Nasrin; Wu, Steve W.

2015-01-01

Fourteen healthy children (13.8 ± 2.2 years, range 10–16; M:F = 5:9) received 30 Hz intermittent theta burst transcranial magnetic stimulation (iTBS) with a stimulation intensity of 70% of resting motor threshold (RMT) with a total of 300 (iTBS300) pulses. All volunteers were free of neurologic, psychiatric and serious medical illnesses, not taking any neuropsychiatric medications, and did not have any contraindications to transcranial magnetic stimulation. Changes in the mean amplitudes of motor-evoked potentials from baseline following iTBS were expressed as a ratio and assessed from 1 to 10 min (BLOCK1) and 1–30 min (BLOCK2) using repeated-measures analysis of variance. All 14 subjects completed iTBS300 over the dominant primary motor cortex (M1) without any clinically reported adverse events. ITBS300 produced significant M1 facilitation [F(5, 65) = 3.165, p = 0.01] at BLOCK1 and trend level M1 facilitation at BLOCK2 [F(10, 129) = 1.69, p = 0.089]. Although iTBS300 (stimulation duration of 92 s at 70% RMT) delivered over M1 in typically developed children was well-tolerated and produced on average significant facilitatory changes in cortical excitability, the post-iTBS300 neurophysiologic response was variable in our small sample. ITBS300-induced changes may represent a potential neuroplastic biomarker in healthy children and those with neuro-genetic or neuro-psychiatric disorders. However, a larger sample size is needed to address safety and concerns of response variability. PMID:25762919

Frontoparietal regions may become hypoactive after intermittent theta burst stimulation over the contralateral homologous cortex in humans.

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He, Xiaofei; Lan, Yue; Xu, Guangqing; Mao, Yurong; Chen, Zhenghong; Huang, Dongfeng; Pei, Zhong

2013-12-01

Brain injury to the dorsal frontoparietal networks, including the posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (DLPFC), commonly cause spatial neglect. However, the interaction of these different regions in spatial attention is unclear. The aim of the present study was to investigate whether hyperexcitable neural networks can cause an abnormal interhemispheric inhibition. The Attention Network Test was used to test subjects following intermittent theta burst stimulation (iTBS) to the left or right frontoparietal networks. During the Attention Network Test task, all subjects tolerated each conditioning iTBS without any obvious iTBS-related side effects. Subjects receiving real-right-PPC iTBS showed significant enhancement in both alerting and orienting efficiency compared with those receiving either sham-right-PPC iTBS or real-left-PPC iTBS. Moreover, subjects exposed to the real-right-DLPFC iTBS exhibited significant improvement in both alerting and executive control efficiency, compared with those exposed to either the sham-right-DLPFC or real-left-DLPFC conditioning. Interestingly, compared with subjects exposed to the sham-left-PPC stimuli, subjects exposed to the real-left-PPC iTBS had a significant deficit in the orienting index. The present study indicates that iTBS over the contralateral homologous cortex may induce the hypoactivity of the right PPC through interhemispheric competition in spatial orienting attention.

Interaction of motor training and intermittent theta burst stimulation in modulating motor cortical plasticity: influence of BDNF Val66Met polymorphism.

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Lee, Mina; Kim, Song E; Kim, Won Sup; Lee, Jungyeun; Yoo, Hye Kyung; Park, Kee-Duk; Choi, Kyoung-Gyu; Jeong, Seon-Yong; Kim, Byung Gon; Lee, Hyang Woon

2013-01-01

Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.

Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following bilateral sequential theta burst magnetic stimulation.

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Vuksanović, Jasmina; Jelić, Milan B; Milanović, Sladjan D; Kačar, Katarina; Konstantinović, Ljubica; Filipović, Saša R

2015-01-01

In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere (RH), by transcranial magnetic stimulation (TMS) or similar methods, can induce improvement in language functions. The supposed mechanism behind this improvement is a release of preserved left hemisphere (LH) language networks from RH transcallosal inhibition. Direct stimulation of the damaged LH can sometimes bring similar results too. Therefore, we developed a novel treatment approach that combined direct LH (Broca's area (BA)) stimulation, by intermittent theta burst stimulation (TBS), with homologue RH area's inhibition, by continuous TBS. We present the results of application of 15 daily sessions of the described treatment approach in a right-handed patient with chronic post-stroke non-fluent aphasia. The intervention appeared to improve several language functions, but most notably propositional speech, semantic fluency, short-term verbal memory, and verbal learning. Bilateral TBS modulation of activation of the language-related areas of both hemispheres seems to be a feasible and promising way to induce recovery in chronic aphasic patients. Due to potentially cumulative physiological effects of bilateral stimulation, the improvements may be even greater than following unilateral interventions.

Effects of intermittent theta-burst stimulation on practice-related changes in fast finger movements in healthy subjects.

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Agostino, Rocco; Iezzi, Ennio; Dinapoli, Loredana; Suppa, Antonio; Conte, Antonella; Berardelli, Alfredo

2008-08-01

In this paper we investigated the effects of intermittent theta-burst stimulation (iTBS) applied to the primary motor cortex on practice-related changes in motor performance. Seventeen healthy subjects underwent two experimental sessions, one testing real iTBS and the other testing sham iTBS. Before and after both iTBS sessions, the subjects practiced fast right index-finger abductions for a few minutes. As measures of cortical excitability we calculated resting motor threshold and motor-evoked potential amplitude. As measures of practice-related changes we evaluated the mean movement amplitude, peak velocity and peak acceleration values for each block. When subjects practiced the movement task, the three variables measuring practice-related changes improved to a similar extent during real and sham iTBS whereas cortical excitability increased only during real iTBS. In a further group of five healthy subjects we investigated the effect of real and sham iTBS on changes in motor performance after a longer task practice and found no significant changes in motor performance and retention after real and sham iTBS. From our results overall we conclude that in healthy subjects iTBS applied to the primary motor cortex leaves practice-related changes in an index finger abduction task unaffected. We suggest that iTBS delivered over the primary motor cortex is insufficient to alter motor performance because early motor learning probably engages a wide cortical and subcortical network.

Modulation of inhibitory activity markers by intermittent theta-burst stimulation in rat cortex is NMDA-receptor dependent.

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Labedi, Adnan; Benali, Alia; Mix, Annika; Neubacher, Ute; Funke, Klaus

2014-01-01

Intermittent theta-burst stimulation (iTBS) applied via transcranial magnetic stimulation has been shown to increase cortical excitability in humans. In the rat brain it strongly reduced the number of neurons expressing the 67-kD isoform of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and those expressing the calcium-binding proteins parvalbumin (PV) and calbindin (CB), specific markers of fast-spiking (FS) and non-FS inhibitory interneurons, respectively, an indication of modified cortical inhibition. Since iTBS effects in humans have been shown to be NMDA receptor sensitive, we wondered whether the iTBS-induced changes in the molecular phenotype of interneurons may be also sensitive to glutamatergic synaptic transmission mediated by NMDA receptors. In a sham-controlled fashion, five iTBS-blocks of 600 stimuli were applied to rats either lightly anesthetized by only urethane or by an additional low (subnarcotic) or high dose of the NMDA receptor antagonist ketamine before immunohistochemical analysis. iTBS reduced the number of neurons expressing GAD67, PV and CB. Except for CB, a low dose of ketamine partially prevented these effects while a higher dose almost completely abolished the iTBS effects. Our findings indicate that iTBS modulates the molecular, and likely also the electric, activity of cortical inhibitory interneurons and that the modulation of FS-type but less that of non-FS-type neurons is mediated by NMDA receptors. A combination of iTBS with pharmacological interventions affecting distinct receptor subtypes may thus offer options to enhance its selectivity in modulating the activity of distinct cell types and preventing others from being modulated. Copyright © 2014 Elsevier Inc. All rights reserved.

Interaction of motor training and intermittent theta burst stimulation in modulating motor cortical plasticity: influence of BDNF Val66Met polymorphism.

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Mina Lee

Full Text Available Cortical physiology in human motor cortex is influenced by behavioral motor training (MT as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS. This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance.

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Chung, Sung Wook; Rogasch, Nigel C; Hoy, Kate E; Sullivan, Caley M; Cash, Robin F H; Fitzgerald, Paul B

2018-02-01

Intermittent theta burst stimulation (iTBS) is a noninvasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex. Sixteen healthy participants received iTBS over prefrontal cortex at either 50, 75 or 100% resting motor threshold in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials and oscillations. The n-back task was used to assess changes in working memory performance. The data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS yielded the largest neurophysiological changes. Improvement in reaction time in the 3-back task was supported by the change in alpha power, however, comparison between conditions revealed no significant differences. The assumption that higher intensity results in greater neuromodulatory effects may be false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample. © 2017 Wiley Periodicals, Inc.

Continuous theta-burst stimulation combined with occupational therapy for upper limb hemiparesis after stroke: a preliminary study.

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Yamada, Naoki; Kakuda, Wataru; Kondo, Takahiro; Shimizu, Masato; Sageshima, Masashi; Mitani, Sugao; Abo, Masahiro

2014-12-01

The purpose of this study was to assess the safety, feasibility and efficacy of continuous theta-burst stimulation (cTBS) combined with intensive occupational therapy (OT) for upper limb hemiparesis after stroke. Ten patients with history of stroke and upper limb hemiparesis (age 62.0 ± 11.1 years, time since stroke 95.7 ± 70.2 months, mean ± SD) were studied. Each patient received 13 sessions, each comprising 160 s of cTBS applied to the skull on the area of the non-lesional hemisphere (using a 70-mm figure-8 coil, three pulse bursts at 50 Hz, repeated every 200 ms, i.e., 5 Hz, with total stimulation of 2,400 pulses), followed by intensive OT (comprising 120-min one-to-one training and 120-min self-training) during 15-day hospitalization. The motor function of the affected upper limb was evaluated by Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) on the days of admission and discharge. All patients completed the 15-day protocol without any adverse effects. Treatment significantly increased the FMA score (from 46.6 ± 8.7 to 51.6 ± 8.2 points, p hemiparesis after stroke.

Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial.

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Bulteau, Samuel; Sébille, Veronique; Fayet, Guillemette; Thomas-Ollivier, Veronique; Deschamps, Thibault; Bonnin-Rivalland, Annabelle; Laforgue, Edouard; Pichot, Anne; Valrivière, Pierre; Auffray-Calvier, Elisabeth; Fortin, June; Péréon, Yann; Vanelle, Jean-Marie; Sauvaget, Anne

2017-01-13

The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression

Reversed Effects of Intermittent Theta Burst Stimulation following Motor Training That Vary as a Function of Training-Induced Changes in Corticospinal Excitability

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Tino Stöckel

2015-01-01

Full Text Available Intermittent theta burst stimulation (iTBS has the potential to enhance corticospinal excitability (CSE and subsequent motor learning. However, the effects of iTBS following motor learning are unknown. The purpose of the present study was to explore the effect of iTBS on CSE and performance following motor learning. Therefore twenty-four healthy participants practiced a ballistic motor task for a total of 150 movements. iTBS was subsequently applied to the trained motor cortex (STIM group or the vertex (SHAM group. Performance and CSE were assessed before motor learning and before and after iTBS. Training significantly increased performance and CSE in both groups. In STIM group participants, subsequent iTBS significantly reduced motor performance with smaller reductions in CSE. CSE changes as a result of motor learning were negatively correlated with both the CSE changes and performance changes as a result of iTBS. No significant effects of iTBS were found for SHAM group participants. We conclude that iTBS has the potential to degrade prior motor learning as a function of training-induced CSE changes. That means the expected LTP-like effects of iTBS are reversed following motor learning.

Reversed Effects of Intermittent Theta Burst Stimulation following Motor Training That Vary as a Function of Training-Induced Changes in Corticospinal Excitability.

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Stöckel, Tino; Summers, Jeffery J; Hinder, Mark R

2015-01-01

Intermittent theta burst stimulation (iTBS) has the potential to enhance corticospinal excitability (CSE) and subsequent motor learning. However, the effects of iTBS following motor learning are unknown. The purpose of the present study was to explore the effect of iTBS on CSE and performance following motor learning. Therefore twenty-four healthy participants practiced a ballistic motor task for a total of 150 movements. iTBS was subsequently applied to the trained motor cortex (STIM group) or the vertex (SHAM group). Performance and CSE were assessed before motor learning and before and after iTBS. Training significantly increased performance and CSE in both groups. In STIM group participants, subsequent iTBS significantly reduced motor performance with smaller reductions in CSE. CSE changes as a result of motor learning were negatively correlated with both the CSE changes and performance changes as a result of iTBS. No significant effects of iTBS were found for SHAM group participants. We conclude that iTBS has the potential to degrade prior motor learning as a function of training-induced CSE changes. That means the expected LTP-like effects of iTBS are reversed following motor learning.

A Data-Driven Approach to Responder Subgroup Identification after Paired Continuous Theta Burst Stimulation

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Tonio Heidegger

2017-08-01

Full Text Available Background: Modulation of cortical excitability by transcranial magnetic stimulation (TMS is used for investigating human brain functions. A common observation is the high variability of long-term depression (LTD-like changes in human (motor cortex excitability. This study aimed at analyzing the response subgroup distribution after paired continuous theta burst stimulation (cTBS as a basis for subject selection.Methods: The effects of paired cTBS using 80% active motor threshold (AMT in 31 healthy volunteers were assessed at the primary motor cortex (M1 corresponding to the representation of the first dorsal interosseous (FDI muscle of the left hand, before and up to 50 min after plasticity induction. The changes in motor evoked potentials (MEPs were analyzed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM and computed ABC analysis.Results: The probability density distribution of the MEP changes from baseline was tri-modal, showing a clear separation at 80.9%. Subjects displaying at least this degree of LTD-like changes were n = 6 responders. By contrast, n = 7 subjects displayed a paradox response with increase in MEP. Reassessment using ABC analysis as alternative approach led to the same n = 6 subjects as a distinct category.Conclusion: Depressive effects of paired cTBS using 80% AMT endure at least 50 min, however, only in a small subgroup of healthy subjects. Hence, plasticity induction by paired cTBS might not reflect a general mechanism in human motor cortex excitability. A mathematically supported criterion is proposed to select responders for enrolment in assessments of human brain functional networks using virtual brain lesions.

Continuous and intermittent transcranial magnetic theta burst stimulation modify tactile learning performance and cortical protein expression in the rat differently.

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Mix, Annika; Benali, Alia; Eysel, Ulf T; Funke, Klaus

2010-11-01

Repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability in a stimulus-frequency-dependent manner. Two kinds of theta burst stimulation (TBS) [intermittent TBS (iTBS) and continuous TBS (cTBS)] modulate human cortical excitability differently, with iTBS increasing it and cTBS decreasing it. In rats, we recently showed that this is accompanied by changes in the cortical expression of proteins related to the activity of inhibitory neurons. Expression levels of the calcium-binding protein parvalbumin (PV) and of the 67-kDa isoform of glutamic acid decarboxylase (GAD67) were strongly reduced following iTBS, but not cTBS, whereas both increased expression of the 65-kDa isoform of glutamic acid decarboxylase. In the present study, to investigate possible functional consequences, we applied iTBS and cTBS to rats learning a tactile discrimination task. Conscious rats received either verum or sham rTMS prior to the task. Finally, to investigate how rTMS and learning effects interact, protein expression was determined for cortical areas directly involved in the task and for those either not, or indirectly, involved. We found that iTBS, but not cTBS, improved learning and strongly reduced cortical PV and GAD67 expression. However, the combination of learning and iTBS prevented this effect in those cortical areas involved in the task, but not in unrelated areas. We conclude that the improved learning found following iTBS is a result of the interaction of two effects, possibly in a homeostatic manner: a general weakening of inhibition mediated by the fast-spiking interneurons, and re-established activity in those neurons specifically involved in the learning task, leading to enhanced contrast between learning-induced and background activity. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Intermittent Theta-Burst Stimulation of the Right Dorsolateral Prefrontal Cortex to Promote Metaphor Comprehension in Parkinson Disease: A Case Study.

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Tremblay, Christina; Monetta, Laura; Langlois, Mélanie; Schneider, Cyril

2016-01-01

This single-case research-designed study explored whether intermittent theta-burst stimulation (iTBS) of the right dorsolateral prefrontal cortex (DLPFC) could improve metaphor comprehension in people with Parkinson disease (PD) and language impairments. A right-handed participant with PD diagnosed 9 years ago, receiving long-term treatment with levodopa, and with metaphor comprehension impairment was recruited to undergo 10 sessions of sham stimulation (in 2wk), a washout period (6wk), and then 10 sessions of iTBS (in 2wk). Clinical scores of metaphor comprehension and motor evaluation (Unified Parkinson Disease Rating Scale part III) and transcranial magnetic stimulation to test the excitability of the primary motor cortex (M1) were used at baseline, postsham, post-iTBS, and at 3 follow-ups (8, 14, and 20wk post-iTBS). Metaphor comprehension was improved after iTBS, and the highest scores were obtained 8 weeks later (P=.01). This improvement was correlated with the increase of the right M1 excitability (r=-.86, P=.03) and with the decrease of transcallosal inhibition latency from the left to the right hemisphere (r=-.88, P=.02). Sham yielded no effect (P>.05). Administration of iTBS over the right DLPFC improved metaphor comprehension likely by a long-term influence on brain synaptic plasticity, including improvement of interhemispheric dialogue. More studies are warranted to confirm these findings in larger samples of participants with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Complex modulation of fingertip forces during precision grasp and lift after theta burst stimulation over the dorsal premotor cortex

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Drljačić Dragana

2017-01-01

Full Text Available Background/Aim. Adaptive control and fingertip force synchronization of precise grasp stability during unimanual manipulation of small objects represents an illustrative example of highly fractionated movements that are foundation of fine motor control. It is assumed that this process is controlled by several motor areas of the frontal lobe, particularly applicable to the primary motor (M-1 and dorsal premotor cortex (PMd. Aiming to examine the role of PMd during fine coordination of fingertip forces we applied theta burst repetitive magnetic stimulation (TBS to disrupt neural processing in that cortical area. Methods. Using a single-blind, randomized, crossover design, 10 healthy subjects (29 ± 3.9 years received single sessions of continuous TBS (cTBS600, intermittent TBS (iTBS600, or sham stimulation, separate from one another at least one week, over the PMd region of dominant hemisphere. Precision grasp and lift were assessed by instrumented device, recording grip (G and load (L forces, during three manipulation tasks (ramp-and-hold, oscillation force producing and simple lifting tasks, with each hand separately, before and after interventions. Results. We observed the improvement of task performance related to constant error (CE in oscillation task with the dominant hand (DH after the iTBS (p = 0.009. On the contrary, the cTBS reduced variable error (VE for non-dominant hand (NH, p = 0.005. Considering force coordination we found that iTBS worsened variables for NH (G/L ratio, p = 0.017; cross-correlation of the G and L, p = 0.047; Gain, p = 0.047. Conclusion. These results demonstrate the ability of TBS to modulate fingertip forces during precision grasping and lifting, when applied over PMd. These findings support the role of PMd in human motor control and forces generation required to hold small objects stable in our hands.

Continuous theta burst stimulation facilitates the clearance efficiency of the glymphatic pathway in a mouse model of sleep deprivation.

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Liu, Dong-Xu; He, Xia; Wu, Dan; Zhang, Qun; Yang, Chao; Liang, Feng-Yin; He, Xiao-Fei; Dai, Guang-Yan; Pei, Zhong; Lan, Yue; Xu, Guang-Qing

2017-07-13

Sleep deprivation (SD) is a common condition associated with a variety of nervous system diseases, and has a negative impact on emotional and cognitive function. Continuous theta burst stimulation (cTBS) is known to improve cognition and emotion function in normal situations as well as in various types of dysfunction, but the mechanism remains unknown. We used two-photon in vivo imaging to explore the effect of cTBS on glymphatic pathway clearance in normal and SD C57BL/6J mice. Aquaporin-4 (AQP4) polarization was detected by immunofluorescence. Anxiety-like behaviors was measured using open field tests. We found that SD reduced influx efficiency along the peri-vascular space (PVS), disturbed AQP4 polarization and induced anxiety-like behaviors. CTBS significantly attenuated the decrease in efficiency of solute clearance usually incurred with SD, restored the loss of AQP4 polarization and improved anxiety-like behavior in SD animals. Our results implied that cTBS had the potential to protect against neuronal dysfunction induced by sleep disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous theta burst stimulation of angular gyrus reduces subjective recollection.

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Yasemin Yazar

Full Text Available The contribution of lateral parietal regions such as the angular gyrus to human episodic memory has been the subject of much debate following widespread observations of left parietal activity in healthy volunteers during functional neuroimaging studies of memory retrieval. Patients with lateral parietal lesions are not amnesic, but recent evidence indicates that their memory abilities may not be entirely preserved. Whereas recollection appears intact when objective measures such as source accuracy are used, patients often exhibit reduced subjective confidence in their accurate recollections. When asked to recall autobiographical memories, they may produce spontaneous narratives that lack richness and specificity, but can remember specific details when prompted. Two distinct theoretical accounts have been proposed to explain these results: that the patients have a deficit in the bottom-up capturing of attention by retrieval output, or that they have an impairment in the subjective experience of recollection. The present study aimed to differentiate between these accounts using continuous theta burst stimulation (cTBS in healthy participants to disrupt function of specific left parietal subregions, including angular gyrus. Inconsistent with predictions of the attentional theory, angular gyrus cTBS did not result in greater impairment of free recall than cued recall. Supporting predictions of the subjective recollection account, temporary disruption of angular gyrus was associated with highly accurate source recollection accuracy but a selective reduction in participants' rated source confidence. The findings are consistent with a role for angular gyrus in the integration of memory features into a conscious representation that enables the subjective experience of remembering.

Reduction in cortical parvalbumin expression due to intermittent theta-burst stimulation correlates with maturation of the perineuronal nets in young rats.

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Mix, Annika; Hoppenrath, Kathrin; Funke, Klaus

2015-01-01

We recently showed that intermittent theta-burst stimulation (iTBS) using transcranial magnetic stimulation strongly reduces the number of rat neocortical interneurons expressing glutamic acid decarboxylase 67 kDa (GAD67) and parvalbumin (PV), indicating changed activity of fast-spiking (FS) interneurons. In advance of in vitro studies intended to characterize changes in electrical properties of FS interneurons under these conditions, we tested whether the iTBS effect is age-dependent. Conscious Sprague-Dawley rats aged between 28 and 90 days received three blocks of iTBS at 15 min intervals. We found that iTBS-related reduction in PV+ cells was absent up to an age of 32 days, then gradually increased, and approached a maximum of about 40% reduction at an age of about 40 days. The relative number of cells expressing PV (PV+, 8-9%) did not change with age in sham-controls and also the increase in cortical c-Fos expression induced by iTBS was not principally age-dependent. However, a prominent growth of the perineuronal nets, typically surrounding the PV+ cells, exactly paralleled the increase in the iTBS effect. Based on these findings, we conclude that the functional development of the inhibitory network of PV+ interneurons with regard to intracortical synaptic connectivity is not sufficiently matured in rats younger than 35 d to enable activity-dependent modifications during iTBS. Outgrowth of the perineuronal nets and associated maturation of excitatory cortical inputs, as is characteristic for the critical cortical period, may take place before PV+ interneurons can be sufficiently activated via repetitive transcranial magnetic stimulation, allowing plastic changes of molecular phenotype and likely also synaptic plasticity. © 2014 Wiley Periodicals, Inc.

Long lasting effects of daily theta burst rTMS sessions in the human amblyopic cortex.

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Clavagnier, Simon; Thompson, Benjamin; Hess, Robert F

2013-11-01

It has been reported that a single session of 1 Hz or 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the visual cortex can temporarily improve contrast sensitivity in adults with amblyopia. More recently, continuous theta burst stimulation (cTBS) of the visual cortex has been found to improve contrast sensitivity in observers with normal vision. The aims of this study were to assess whether cTBS of the visual cortex could improve contrast sensitivity in adults with amblyopia and whether repeated sessions of cTBS would lead to more pronounced and/or longer lasting effects. cTBS was delivered to the visual cortex while patients viewed a high contrast stimulus with their non-amblyopic eye. This manipulation was designed to bias the effects of cTBS toward inputs from the amblyopic eye. Contrast sensitivity was measured before and after stimulation. The effects of one cTBS session were measured in five patients and the effects of five consecutive daily sessions were measured in four patients. Three patients were available for follow-up at varying intervals after the final session. cTBS improved amblyopic eye contrast sensitivity to high spatial frequencies (P enduring visual function improvements in adults with amblyopia. Copyright © 2013 Elsevier Inc. All rights reserved.

DOES THE INFERIOR FRONTAL SULCUS PLAY A FUNCTIONAL ROLE IN DECEPTION? A NEURONAVIGATED THETA-BURST TRANSCRANIAL MAGNETIC STIMULATION STUDY

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Bruno eVerschuere

2012-10-01

Full Text Available Background. By definition, lying involves withholding the truth. Response inhibition may therefore be the cognitive function at the heart of deception. Neuroimaging research has shown that the same brain region that is activated during response inhibition tasks, namely the inferior frontal region, is also activated during deception paradigms. This led to the hypothesis that the inferior frontal region is the neural substrate critically involved in withholding the truth. Objective. We critically examine the functional necessity of the inferior frontal region in withholding the truth during deception. Method. We experimentally manipulated the neural activity level in right inferior frontal sulcus (IFS by means of neuronavigated continuous theta burst stimulation (cTBS. Individual structural magnetic resonance brain images (MRI were used to allow precise stimulation in each participant. Twenty-six participants answered autobiographical questions truthfully or deceptively before and after sham and real cTBS. Results. Deception was reliably associated with more errors, longer and more variable response times than truth telling. Despite the potential role of IFS in deception as suggested by neuroimaging data, the cTBS-induced disruption of right IFS did not affect response times or error rates, when compared to sham stimulation. Conclusions. The present findings do not support the hypothesis that the right inferior frontal sulcus is critically involved in deception.

Modulation of left primary motor cortex excitability after bimanual training and intermittent theta burst stimulation to left dorsal premotor cortex.

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Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

2014-03-15

Bimanual visuomotor movement training (BMT) enhances the excitability of human preparatory premotor and primary motor (M1) cortices compared to unimanual movement. This occurs when BMT involves mirror symmetrical movements of both upper-limbs (in-phase) but not with non-symmetrical movements (anti-phase). The neural mechanisms mediating the effect of BMT is unclear, but may involve interhemispheric connections between homologous M1 representations as well as the dorsal premotor cortices (PMd). The purpose of this study is to assess how intermittent theta burst stimulation (iTBS) of the left PMd affects left M1 excitability, and the possible combined effects of iTBS to left PMd applied before a single session of BMT. Left M1 excitability was quantified using transcranial magnetic stimulation (TMS) in terms of both the amplitudes and spatial extent of motor evoked potentials (MEPs) for the extensor carpi radialis (ECR) before and multiple time points following (1) BMT, (2) iTBS to left PMd or (3) iTBS to left PMd and BMT. Although there was not a greater increase in either specific measure of M1 excitability due to the combination of the interventions, iTBS applied before BMT showed that both the spatial extent and global MEP amplitude for the ECR became larger in parallel, whereas the spatial extent was enhanced with BMT alone and global MEP amplitude was enhanced with iTBS to left PMd alone. These results suggest that the modulation of rapid functional M1 excitability associated with BMT and iTBS of the left PMd could operate under related early markers of neuro-plastic mechanisms, which may be expressed in concurrent and distinct patterns of M1 excitability. Critically, this work may guide rehabilitation training and stimulation techniques that modulate cortical excitability after brain injury. Copyright © 2013 Elsevier B.V. All rights reserved.

Reduced Performance During a Sentence Repetition Task by Continuous Theta-Burst Magnetic Stimulation of the Pre-supplementary Motor Area

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Dietrich, Susanne; Hertrich, Ingo; Müller-Dahlhaus, Florian; Ackermann, Hermann; Belardinelli, Paolo; Desideri, Debora; Seibold, Verena C.; Ziemann, Ulf

2018-01-01

The pre-supplementary motor area (pre-SMA) is engaged in speech comprehension under difficult circumstances such as poor acoustic signal quality or time-critical conditions. Previous studies found that left pre-SMA is activated when subjects listen to accelerated speech. Here, the functional role of pre-SMA was tested for accelerated speech comprehension by inducing a transient “virtual lesion” using continuous theta-burst stimulation (cTBS). Participants were tested (1) prior to (pre-baseline), (2) 10 min after (test condition for the cTBS effect), and (3) 60 min after stimulation (post-baseline) using a sentence repetition task (formant-synthesized at rates of 8, 10, 12, 14, and 16 syllables/s). Speech comprehension was quantified by the percentage of correctly reproduced speech material. For high speech rates, subjects showed decreased performance after cTBS of pre-SMA. Regarding the error pattern, the number of incorrect words without any semantic or phonological similarity to the target context increased, while related words decreased. Thus, the transient impairment of pre-SMA seems to affect its inhibitory function that normally eliminates erroneous speech material prior to speaking or, in case of perception, prior to encoding into a semantically/pragmatically meaningful message. PMID:29896086

Reduced Performance During a Sentence Repetition Task by Continuous Theta-Burst Magnetic Stimulation of the Pre-supplementary Motor Area

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Susanne Dietrich

2018-05-01

Full Text Available The pre-supplementary motor area (pre-SMA is engaged in speech comprehension under difficult circumstances such as poor acoustic signal quality or time-critical conditions. Previous studies found that left pre-SMA is activated when subjects listen to accelerated speech. Here, the functional role of pre-SMA was tested for accelerated speech comprehension by inducing a transient “virtual lesion” using continuous theta-burst stimulation (cTBS. Participants were tested (1 prior to (pre-baseline, (2 10 min after (test condition for the cTBS effect, and (3 60 min after stimulation (post-baseline using a sentence repetition task (formant-synthesized at rates of 8, 10, 12, 14, and 16 syllables/s. Speech comprehension was quantified by the percentage of correctly reproduced speech material. For high speech rates, subjects showed decreased performance after cTBS of pre-SMA. Regarding the error pattern, the number of incorrect words without any semantic or phonological similarity to the target context increased, while related words decreased. Thus, the transient impairment of pre-SMA seems to affect its inhibitory function that normally eliminates erroneous speech material prior to speaking or, in case of perception, prior to encoding into a semantically/pragmatically meaningful message.

Continuous theta-burst stimulation may improve visuospatial neglect via modulating the attention network: a randomized controlled study.

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Fu, Wei; Cao, Lei; Zhang, Yanming; Huo, Su; Du, JuBao; Zhu, Lin; Song, Weiqun

2017-05-01

Visuospatial neglect (VSN) is devastating and common after stroke, and is thought to involve functional disturbance of the attention network. Non-invasive theta-burst stimulation (TBS) may help restore the normal function of attention network, therefore facilitating recovery from VSN. This study investigated the effects of continuous TBS on resting-state functional connectivity (RSFC) in the attention network, and behavioral performances of patients with VSN after stroke. Twelve patients were randomly assigned to receive 10-day cTBS of the left posterior parietal cortex delivered at 80% (the cTBS group), or 40% (the active control group) of the resting motor threshold. Both groups received daily visual scanning training and motor function treatment. Resting-state functional MRI (fMRI) and behavioral tests including line bisection test and star cancelation test were conducted at baseline and after the treatment. At baseline, the two groups showed comparable results in the resting-state fMRI experiments and behavioral tests. After treatment, the cTBS group showed lower functional connectivity between right temporoparietal junction (TPJ) and right anterior insula, and between right superior temporal sulcus and right anterior insula, as compared with the active control group; both groups showed improvement in the behavioral tests, with the cTBS group showing larger changes from baseline than the active control group. cTBS of the left posterior parietal cortex in patients with VSN may induce changes in inter-regional RSFC in the right ventral attention network. These changes may be associated with improved recovery of behavioral deficits after behavioral training. The TPJ and superior temporal sulcus may play crucial roles in recovery from VSN.

Safety and Tolerability of Theta Burst Stimulation versus Single and Paired Pulse Transcranial Magnetic Stimulation: A Comparative Study of 165 Pediatric Subjects

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Yaejee H Hong

2015-02-01

Full Text Available Background: Although single- and paired-pulse (sp/pp transcranial magnetic stimulation (TMS studies are considered minimal risk in adults and children, the safety profile for theta-burst TMS (TBS is unknown.Objective: In this comparative analysis, we explored the rate, severity, and specific symptoms of TMS-related adverse effects (AEs between sp/ppTMS and TBS in subjects between ages 6 and 18 years.Method: Data from 165 participants from 2009-2014 were analyzed. Assessment of AEs was performed based on baseline and post-TMS administration of a symptom-based questionnaire that rated AEs on a 5-level ordinal scale (minimal, mild, moderate, marked, severe. AE rates and severity were compared using Chi Square or Fisher’s Exact Test depending on data characteristics.Result: Overall, no seizures or severe-rated AEs were reported by 165 pediatric participants. The rate of AE in all TBS sessions was 10.5% (n=76, 95% CI: 4.7 - 19.7%, whereas the rate of AE in all sp/ppTMS sessions was 12.4% (n=89, 95% CI: 6.3 - 21.0%. There was no statistical difference in AE rates between TBS and sp/ppTMS (p=0.71. In all sp/ppTMS and TBS sessions, 20 subjects reported a total of 35 AEs, among these 31 (~88.6% were rated as minimal or mild. There was no difference in the severity of AE between TBS and sp/ppTMS (p=1.0. Only one of 76 TBS participants reported an AE rated as more than minimal/mild.Conclusion: Our comparative analysis showed that TBS appears to be as safe as sp/ppTMS in terms of AE rate and severity. This report supports further investigation of TBS in children.

Bilateral primary motor cortex circuitry is modulated due to theta burst stimulation to left dorsal premotor cortex and bimanual training.

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Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

2015-08-27

Motor preparatory and execution activity is enhanced after a single session of bimanual visuomotor training (BMT). Recently, we have shown that increased primary motor cortex (M1) excitability occurs when BMT involves simultaneous activation of homologous muscles and these effects are enhanced when BMT is preceded by intermittent theta burst stimulation (iTBS) to the left dorsal premotor cortex (lPMd). The neural mechanisms underlying these modulations are unclear, but may include interhemispheric interactions between homologous M1s and connectivity with premotor regions. The purpose of this study was to investigate the possible intracortical and interhemispheric modulations of the extensor carpi radials (ECR) representation in M1 bilaterally due to: (1) BMT, (2) iTBS to lPMd, and (3) iTBS to lPMd followed by BMT. This study tests three related hypotheses: (1) BMT will enhance excitability within and between M1 bilaterally, (2) iTBS to lPMd will primarily enhance left M1 (lM1) excitability, and (3) the combination of these interventions will cause a greater enhancement of bilateral M1 excitability. We used single and paired-pulse transcranial magnetic stimulation (TMS) to quantify M1 circuitry bilaterally. The results demonstrate the neural mechanisms underlying the early markers of rapid functional plasticity associated with BMT and iTBS to lPMd primarily relate to modulations of long-interval inhibitory (i.e. GABAB-mediated) circuitry within and between M1s. This work provides novel insight into the underlying neural mechanisms involved in M1 excitability changes associated with BMT and iTBS to lPMd. Critically, this work may inform rehabilitation training and stimulation techniques that modulate cortical plasticity after brain injury. Copyright © 2015. Published by Elsevier B.V.

Is sham cTBS real cTBS? The effect on EEG dynamics

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Alexander eOpitz

2015-01-01

Full Text Available Increasing sensitivity of modern evaluation tools allows for the study of weaker electric stimulation effects on neural populations. In the current study we examined the effects of sham continuous theta burst (cTBS transcranial magnetic stimulation to the left dorsolateral prefrontal cortex (DLPFC upon somatosensory evoked potentials (SEP and frontal-parietal phase coupling of alpha and beta bands. Sham TMS results in an induced electric field amplitude roughly 5% that of real TMS with a similar spatial extent in cortex. Both real and sham cTBS reduced the amplitude of the frontal P14-N30 SEP and increased local phase coupling in the alpha-beta frequency bands of left frontal cortex. In addition, both sham and real cTBS increased frontal-parietal phase coupling in the alpha-beta bands concomitant with an increase in amplitude of parietal P50-N70 complex. These data suggest that weak electric fields from sham cTBS can affect both local and downstream neuronal circuits, though in a different manner than high strength TMS.

Is sham cTBS real cTBS? The effect on EEG dynamics.

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Opitz, Alexander; Legon, Wynn; Mueller, Jerel; Barbour, Aaron; Paulus, Walter; Tyler, William J

2014-01-01

Increasing sensitivity of modern evaluation tools allows for the study of weaker electric stimulation effects on neural populations. In the current study we examined the effects of sham continuous theta burst (cTBS) transcranial magnetic stimulation to the left dorsolateral prefrontal cortex (DLPFC) upon somatosensory evoked potentials (SEP) and frontal-parietal phase coupling of alpha and beta bands. Sham TMS results in an induced electric field amplitude roughly 5% that of real TMS with a similar spatial extent in cortex. Both real and sham cTBS reduced the amplitude of the frontal P14-N30 SEP and increased local phase coupling in the alpha-beta frequency bands of left frontal cortex. In addition, both sham and real cTBS increased frontal-parietal phase coupling in the alpha-beta bands concomitant with an increase in amplitude of parietal P50-N70 complex. These data suggest that weak electric fields from sham cTBS can affect both local and downstream neuronal circuits, though in a different manner than high strength TMS.

Alterations of the amplitude of low-frequency fluctuation in healthy subjects with theta-burst stimulation of the cortex of the suprahyoid muscles.

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Ruan, Xiuhang; Xu, Guangqing; Gao, Cuihua; Liu, Lingling; Liu, Yanli; Jiang, Lisheng; Chen, Xin; Yu, Shaode; Jiang, Xinqing; Lan, Yue; Wei, Xinhua

2017-12-04

Theta burst stimulation (TBS) has emerged as a promising tool for the treatment of swallowing disorders; however, the short-term after-effects of brain activation induced by TBS remain unknown. Here, we measured the changes in spontaneous brain activation using the amplitude of low-frequency fluctuation (ALFF) approach in subjects who underwent different TBS protocols. Sixty right-handed healthy participants (male, n=30; female, n=30; mean age=23.5y) were recruited in this study and randomly assigned to three groups that underwent three different TBS protocols. In group 1, continuous TBS (cTBS) was positioned on the left hemisphere of the suprahyoid muscle cortex. For group 2, intermittent TBS (iTBS) was placed on the left hemisphere of the suprahyoid muscle cortex. Group 3 underwent combined cTBS/iTBS protocols in which iTBS on the right hemisphere was performed immediately after completing cTBS on the left suprahyoid muscle cortex. Compared to pre-TBS, post-cTBS showed decreased ALFF in the anterior cingulate gyrus (BA 32); post-iTBS induced an increase in ALFF in the bilateral precuneus (BA 7); and post-cTBS/iTBS induced a decrease in ALFF in the brainstem, and resulted in increased ALFF in the middle cingulate gyrus (BA 24) as well as the left precentral gyrus (BA 6). Compared the effect of post-TBS protocols, increased ALFF was found in left posterior cerebellum lobe and left inferior parietal lobule (BA 40) (post-cTBS vs post-iTBS), and decreased ALFF exhibited in paracentral lobule (BA 4) (post-iTBS vs post-cTBS/iTBS). These findings indicate that multiple brain areas involved in swallowing regulation after stimulation of TBS over the suprahyoid muscles. cTBS induces decreased after-effects while iTBS results in increased after-effects on spontaneous brain activation. Moreover, iTBS can eliminate the after-effects of cTBS applied on the contralateral swallowing cortex and alter the activity of contralateral motor cortex and brainstem. Our findings provide a

Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion.

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Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

2016-01-01

Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo-in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28) and older animals (PD40-62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

The Impact of Single Session Intermittent Theta-Burst Stimulation over the Dorsolateral Prefrontal Cortex and Posterior Superior Temporal Sulcus on Adults with Autism Spectrum Disorder

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Hsing-Chang Ni

2017-05-01

Full Text Available Intermittent theta burst stimulation (iTBS, a patterned repetitive transcranial magnetic stimulation, was applied over the posterior superior temporal sulcus (pSTS or dorsolateral prefrontal cortex (DLPFC to explore its impact in adults with autism spectrum disorder (ASD. Among 25 adults with ASD, 19 (mean age: 20.8 years completed the randomized, sham-controlled, crossover trial. Every participant received iTBS over the bilateral DLPFC, bilateral pSTS and inion (as a sham control stimulation in a randomized order with a 1-week interval. Neuropsychological functions were assessed using the Conners' Continuous Performance Test (CCPT and the Wisconsin Card Sorting Test (WCST. Behavioral outcomes were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS and the Social Responsiveness Scale (SRS. In comparison to that in the sham stimulation, the reaction time in the CCPT significantly decreased following single DLPFC session (p = 0.04, effect size = 0.71 while there were no significant differences in the CCPT and WCST following single pSTS session. Besides, the results in behavioral outcomes were inconsistent and had discrepancy between reports of parents and patients. In conclusion, a single session of iTBS over the bilateral DLPFC may alter the neuropsychological function in adults with ASD. The impacts of multiple-sessions iTBS over the DLPFC or pSTS deserve further investigations.

rTMS of the dorsomedial prefrontal cortex for major depression: safety, tolerability, effectiveness, and outcome predictors for 10 Hz versus intermittent theta-burst stimulation.

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Bakker, Nathan; Shahab, Saba; Giacobbe, Peter; Blumberger, Daniel M; Daskalakis, Zafiris J; Kennedy, Sidney H; Downar, Jonathan

2015-01-01

Conventional rTMS protocols for major depression commonly employ stimulation sessions lasting >30 min. However, recent studies have sought to improve costs, capacities, and outcomes by employing briefer protocols such as theta burst stimulation (iTBS). To compare safety, effectiveness, and outcome predictors for DMPFC-rTMS with 10 Hz (30 min) versus iTBS (6 min) protocols, in a large, naturalistic, retrospective case series. A chart review identified 185 patients with a medication-resistant major depressive episode who underwent 20-30 sessions of DMPFC-rTMS (10 Hz, n = 98; iTBS, n = 87) at a single Canadian clinic from 2011 to 2014. Clinical characteristics of 10 Hz and iTBS patients did not differ prior to treatment, aside from significantly higher age in iTBS patients. A total 7912 runs of DMPFC-rTMS (10 Hz, 4274; iTBS, 3638) were administered, without any seizures or other serious adverse events, and no significant differences in rates of premature discontinuation between groups. Dichotomous outcomes did not differ significantly between groups (Response/remission rates: Beck Depression Inventory-II: 10 Hz, 40.6%/29.2%; iTBS, 43.0%/31.0%. 17-item Hamilton Rating Scale for Depression: 10 Hz, 50.6%/38.5%; iTBS, 48.5%/27.9%). On continuous outcomes, there was no significant difference between groups in pre-treatment or post-treatment scores, or percent improvement on either measure. Mixed-effects modeling revealed no significant group-by-time interaction on either measure. Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears comparable. Randomized trials comparing 10 Hz to iTBS may be warranted. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Continuous theta-burst stimulation over the dorsal premotor cortex interferes with associative learning during object lifting.

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Nowak, Dennis A; Berner, Julia; Herrnberger, Bärbel; Kammer, Thomas; Grön, Georg; Schönfeldt-Lecuona, Carlos

2009-04-01

When lifting objects of different mass, humans scale grip force according to the expected mass. In this context, humans are able to associate a sensory cue, such as a colour, to a particular mass of an object and link this association to the grip forces necessary for lifting. Here, we study the role of the dorsal premotor cortex (PMd) in setting-up an association between a colour cue and a particular mass to be lifted. Healthy right-handed subjects used a precision grip between the index finger and thumb to lift two different masses. Colour cues provided information about which of the two masses subjects would have to lift. Subjects first performed a series of lifts with the right hand to establish a stable association between a colour cue and a mass, followed by 20sec of continuous high frequency repetitive trancranial magnetic stimulation using a recently developed protocol (continuous theta-burst stimulation, cTBS) over (i) the left primary motor cortex, (ii) the left PMd and (iii) the left occipital cortex to be commenced by another series of lifts with either the right or left hand. cTBS over the PMd, but not over the primary motor cortex or O1, disrupted the predictive scaling of isometric finger forces based on colour cues, irrespective of whether the right or left hand performed the lifts after the stimulation. Our data highlight the role of the PMd to generalize and maintain associative memory processes relevant for predictive control of grip forces during object manipulation.

Human θ burst stimulation enhances subsequent motor learning and increases performance variability.

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Teo, James T H; Swayne, Orlando B C; Cheeran, Binith; Greenwood, Richard J; Rothwell, John C

2011-07-01

Intermittent theta burst stimulation (iTBS) transiently increases motor cortex excitability in healthy humans by a process thought to involve synaptic long-term potentiation (LTP), and this is enhanced by nicotine. Acquisition of a ballistic motor task is likewise accompanied by increased excitability and presumed intracortical LTP. Here, we test how iTBS and nicotine influences subsequent motor learning. Ten healthy subjects participated in a double-blinded placebo-controlled trial testing the effects of iTBS and nicotine. iTBS alone increased the rate of learning but this increase was blocked by nicotine. We then investigated factors other than synaptic strengthening that may play a role. Behavioral analysis and modeling suggested that iTBS increased performance variability, which correlated with learning outcome. A control experiment confirmed the increase in motor output variability by showing that iTBS increased the dispersion of involuntary transcranial magnetic stimulation-evoked thumb movements. We suggest that in addition to the effect on synaptic plasticity, iTBS may have facilitated performance by increasing motor output variability; nicotine negated this effect on variability perhaps via increasing the signal-to-noise ratio in cerebral cortex.

Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system.

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Nettekoven, Charlotte; Volz, Lukas J; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2014-05-14

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. Copyright © 2014 the authors 0270-6474/14/346849-11$15.00/0.

Intermittent Theta Burst Over M1 May Increase Peak Power of a Wingate Anaerobic Test and Prevent the Reduction of Voluntary Activation Measured with Transcranial Magnetic Stimulation.

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Giboin, Louis-Solal; Thumm, Patrick; Bertschinger, Raphael; Gruber, Markus

2016-01-01

Despite the potential of repetitive transcranial magnetic stimulation (rTMS) to improve performances in patients suffering from motor neuronal afflictions, its effect on motor performance enhancement in healthy subjects during a specific sport task is still unknown. We hypothesized that after an intermittent theta burst (iTBS) treatment, performance during the Wingate Anaerobic Test (WAnT) will increase and supraspinal fatigue following the exercise will be lower in comparison to a control treatment. Ten subjects participated in two randomized experiments consisting of a WAnT 5 min after either an iTBS or a control treatment. We determined voluntary activation (VA) of the right knee extensors with TMS (VATMS) and with peripheral nerve stimulation (VAPNS) of the femoral nerve, before and after the WAnT. T-tests were applied to the WAnT results and a two way within subject ANOVA was applied to VA results. The iTBS treatment increased the peak power and the maximum pedalling cadence and suppressed the reduction of VATMS following the WAnT compared to the control treatment. No behavioral changes related to fatigue (mean power and fatigue index) were observed. These results indicate for the first time that iTBS could be used as a potential intervention to improve anaerobic performance in a sport specific task.

Intermittent θ burst stimulation over primary motor cortex enhances movement-related β synchronisation.

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Hsu, Ya-Fang; Liao, Kwong-Kum; Lee, Po-Lei; Tsai, Yun-An; Yeh, Chia-Lung; Lai, Kuan-Lin; Huang, Ying-Zu; Lin, Yung-Yang; Lee, I-Hui

2011-11-01

The objective of this study is to investigate how transcranial magnetic intermittent theta burst stimulation (iTBS) with a prolonged protocol affects human cortical excitability and movement-related oscillations. Using motor-evoked potentials (MEPs) and movement-related magnetoencephalography (MEG), we assessed the changes of corticospinal excitability and cortical oscillations after iTBS with double the conventional stimulation time (1200 pulses, iTBS1200) over the primary motor cortex (M1) in 10 healthy subjects. Continuous TBS (cTBS1200) and sham stimulation served as controls. iTBS1200 facilitated MEPs evoked from the conditioned M1, while inhibiting MEPs from the contralateral M1 for 30 min. By contrast, cTBS1200 inhibited MEPs from the conditioned M1. Importantly, empirical mode decomposition-based MEG analysis showed that the amplitude of post-movement beta synchronisation (16-26 Hz) was significantly increased by iTBS1200 at the conditioned M1, but was suppressed at the nonconditioned M1. Alpha (8-13 Hz) and low gamma-ranged (35-45 Hz) rhythms were not notably affected. Movement kinetics remained consistent throughout. TBS1200 modulated corticospinal excitability in parallel with the direction of conventional paradigms with modestly prolonged efficacy. Moreover, iTBS1200 increased post-movement beta synchronisation of the stimulated M1, and decreased that of the contralateral M1, probably through interhemispheric interaction. Our results provide insight into the underlying mechanism of TBS and reinforce the connection between movement-related beta synchronisation and corticospinal output. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Intermittent theta burst over M1 may increase peak power of a Wingate anaerobic test and prevent the reduction of voluntary activation measured with transcranial magnetic stimulation

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Louis-Solal Giboin

2016-07-01

Full Text Available Despite the potential of repetitive transcranial magnetic stimulation (rTMS to improve performances in patients suffering from motor neuronal afflictions, its effect on motor performance enhancement in healthy subjects during a specific sport task is still unknown. We hypothesised that after an intermittent theta burst (iTBS treatment, performance during the Wingate Anaerobic Test (WAnT, will increase and supraspinal fatigue following the exercise will be lower in comparison to a control treatment.Ten subjects participated in two randomised experiments consisting of a WAnT 5 minutes after either an iTBS or a control treatment. We determined voluntary activation (VA of the right knee extensors with TMS (VATMS and with peripheral nerve stimulation (VAPNS of the femoral nerve, before and after the WAnT. T-tests were applied to the WAnT results and a 2 way within subject ANOVA was applied to VA results. The iTBS treatment increased the peak power and the maximum pedalling cadence and suppressed the reduction of VATMS following the WAnT compared to the control treatment. No behavioural changes related to fatigue (mean power and fatigue index were observed.These results indicate for the first time that iTBS could be used as a potential intervention to improve anaerobic performance in a sport specific task.

Is theta burst stimulation applied to visual cortex able to modulate peripheral visual acuity?

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Sabrina Brückner

Full Text Available Repetitive transcranial magnetic stimulation is usually applied to visual cortex to explore the effects on cortical excitability. Most researchers therefore concentrate on changes of phosphene threshold, rarely on consequences for visual performance. Thus, we investigated peripheral visual acuity in the four quadrants of the visual field using Landolt C optotypes before and after repetitive stimulation of the visual cortex. We applied continuous and intermittend theta burst stimulation with various stimulation intensities (60%, 80%, 100%, 120% of individual phosphene threshold as well as monophasic and biphasic 1 Hz stimulation, respectively. As an important result, no serious adverse effects were observed. In particular, no seizure was induced, even with theta burst stimulation applied with 120% of individual phosphene threshold. In only one case stimulation was ceased because the subject reported intolerable pain. Baseline visual acuity decreased over sessions, indicating a continuous training effect. Unexpectedly, none of the applied transcranial magnetic stimulation protocols had an effect on performance: no change in visual acuity was found in any of the four quadrants of the visual field. Binocular viewing as well as the use of peripheral instead of foveal presentation of the stimuli might have contributed to this result. Furthermore, intraindividual variability could have masked the TMS- induced effects on visual acuity.

Effects of High Frequency Repeated Transcranial Magnetic Stimulation and Continuous Theta Burst Stimulation on Gambling Reinforcement, Delay Discounting, and Stroop Interference in Men with Pathological Gambling.

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Zack, Martin; Cho, Sang Soo; Parlee, Jennifer; Jacobs, Mark; Li, Crystal; Boileau, Isabelle; Strafella, Antonio

Repeated transcranial magnetic stimulation (rTMS) can reduce cravings and improve cognitive function in substance dependent individuals. Whether these benefits extend to individuals with pathological gambling (PG) is unclear. High-frequency rTMS of the medial prefrontal cortex (PFC) and continuous theta burst stimulation (cTBS) of the right dorsolateral PFC can reduce impulsive choice in healthy volunteers. This study aimed to assess the effects of these two protocols on gambling reinforcement and related responses in otherwise healthy men with PG. Participants (n = 9) underwent active or sham treatments at weekly intervals in a repeated-measures, Latin square design. Subjective and physiological responses were assessed before and after a 15-min slot machine game on each session. Delay discounting and Stroop tasks measured post-game impulsive choice and attentional control. Multivariate analysis of covariance, controlling for winnings on the slot machine under each treatment, found that rTMS reduced the post-game increase in Desire to Gamble; cTBS reduced amphetamine-like effects, and decreased diastolic blood pressure. Treatment had no significant univariate effects on bet size or speed of play in the game; however, a multivariate effect for the two indices suggested that treatment decreased behavioral activation. Neither treatment reduced impulsive choice, while both treatments increased Stroop interference. rTMS and cTBS can reduce gambling reinforcement in non-comorbid men with PG. Separate processes appear to mediate gambling reinforcement and betting behavior as against delay discounting and Stroop interference. Interventions that modify risky as opposed to temporal aspects of decision making may better predict therapeutic response in PG. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychophysiological effects of an iTBS modulated virtual reality challenge including participants with spider phobia.

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Notzon, S; Deppermann, S; Fallgatter, A; Diemer, J; Kroczek, A; Domschke, K; Zwanzger, P; Ehlis, A-C

2015-12-01

Preliminary evidence suggests beneficial effects of transcranial magnetic stimulation (TMS) on anxiety. The objective of this study was to investigate the effects of intermittent theta burst stimulation (iTBS) as a form of TMS on acute anxiety provoked by a virtual reality (VR) scenario. Participants with spider phobia (n=41) and healthy controls (n=42) were exposed to a spider scenario in VR after one session of iTBS over the prefrontal cortex or sham treatment. Participants with spider phobia reacted with more anxiety compared to healthy controls. Their heart rate and skin conductance increased compared to baseline. Contrary to expectations, iTBS did not influence these reactions, but modulated heart rate variability (HRV). Sympathetic influence on HRV showed an increase in the active iTBS group only. This study does not support the idea of beneficial effects of a single session of iTBS on anxiety, although other protocols or repeated sessions might be effective. Copyright © 2015 Elsevier B.V. All rights reserved.

Modulation of iTBS after-effects via concurrent directional TDCS: A proof of principle study.

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Tremblay, Sara; Hannah, Ricci; Rawji, Vishal; Rothwell, John C

Polarising currents can modulate membrane potentials in animals, affecting the after-effect of theta burst stimulation (TBS) on synaptic strength. We examined whether a similar phenomenon could also be observed in human motor cortex (M1) using transcranial direct current stimulation (TDCS) during monophasic intermittent TBS (iTBS). TDCS was applied during posterior-anterior iTBS using three different conditions: posterior-anterior TDCS (anode 3.5 cm posterior to M1, cathode 3.5 cm anterior to M1), anterior-posterior TDCS (cathode 3.5 cm posterior to M1, anode 3.5 cm anterior to M1), and sham TDCS. When the direction of TDCS (posterior-anterior) matched the direction of the electrical field induced by iTBS, we found a 19% non-significant increase in excitability changes in comparison with iTBS combined with sham TDCS. When the TDCS was reversed (anterior-posterior), the excitatory effect of iTBS was abolished. Our findings suggest that excitatory after-effects of iTBS can be modulated by directionally-specific TDCS. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia.

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Duprat, Romain; Wu, Guo-Rong; De Raedt, Rudi; Baeken, Chris

2017-08-09

Accelerated intermittent theta-burst stimulation (aiTBS) anti-depressive working mechanisms are still unclear. Because aiTBS may work through modulating the reward system and the level of anhedonia may influence this modulation, we investigated the effect of aiTBS on reward responsiveness in high and low anhedonic MDD patients. In this registered RCT (NCT01832805), 50 MDD patients were randomised to a sham-controlled cross-over aiTBS treatment protocol over the left dorsolateral prefrontal cortex (DLPFC). Patients performed a probabilistic learning task in fMRI before and after each week of stimulation. Task performance analyses did not show any significant effects of aiTBS on reward responsiveness, nor differences between both groups of MDD patients. However, at baseline, low anhedonic patients displayed higher neural activity in the caudate and putamen. After the first week of aiTBS treatment, in low anhedonic patients we found a decreased neural activity within the reward system, in contrast to an increased activity observed in high anhedonic patients. No changes were observed in reward related neural regions after the first week of sham stimulation. Although both MDD groups showed no differences in task performance, our brain imaging findings suggest that left DLPFC aiTBS treatment modulates the reward system differently according to anhedonia severity.

[The application of high-frequency and iTBS transcranial magnetic stimulation for the treatment of spasticity in the patients presenting with secondary progressive multiple sclerosis].

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Korzhova, J E; Chervyakov, A V; Poydasheva, A G; Kochergin, I A; Peresedova, A V; Zakharova, M N; Suponeva, N A; Chernikova, L A; Piradov, M A

Spasticity is considered to be a common manifestation of multiple sclerosis. Muscle relaxants are not sufficiently effective; more than that, some of them often cause a variety of adverse reactions. Transcranial magnetic stimulation (TMS) can be a promising new tool for the treatment of spasticity. The objective of the present study was to compare the effectiveness of the two TMS protocols: rhythmic (high-frequency) TMS (rTMS) and stimulation with the theta bursts (iTBS) in terms of their ability to reduce spasticity in the patients presenting with multiple sclerosis. Twenty two patients with secondary-progressive multiple sclerosis were pseudo-randomized into two groups: those in the first (high-frequency) group received the treatment with the use of rTMS therapy at a frequency of 10 Hz; the patients of the second group, underwent stimulation with the theta bursts (iTBS). All the patients received 10 sessions of either stimulation applied to the primary motor area (M1) of both legs. The effectiveness of TMS protocols was evaluated before therapy and after 10 sessions of stimulation based on the Modified Ashworth scale (MAS), the expanded disability status scale (EDSS), and the Kurtzke functional scale (Kfs). In addition, the patients were interviewed before treatment, after 10 rTMS sessions, immediately after and within 2 and 12 weeks after the completion of the treatment using questionnaires for the evaluation of spasticity (SESS) , fatigue, and dysfunction of the pelvic organs (severity of defecation and urination disorders), fatigue. The study has demonstrated a significant reduction in spasticity in the patients of both groups at the end of the TMS protocol based on the MAS scale. There was no significant difference between the outcomes of the two protocols. Both had positive effect on the concomitant «non-motor» symptoms (fatigue, dysfunction of the pelvic organs). High-frequency transcranial magnetic stimulation (10 sessions of rTMS therapy at a frequency

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial.

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Blumberger, Daniel M; Vila-Rodriguez, Fidel; Thorpe, Kevin E; Feffer, Kfir; Noda, Yoshihiro; Giacobbe, Peter; Knyahnytska, Yuliya; Kennedy, Sidney H; Lam, Raymond W; Daskalakis, Zafiris J; Downar, Jonathan

2018-04-28

Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression. In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18-65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4-6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary

Interindividual differences in motor network connectivity and behavioral response to iTBS in stroke patients.

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Diekhoff-Krebs, Svenja; Pool, Eva-Maria; Sarfeld, Anna-Sophia; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2017-01-01

Cerebral plasticity-inducing approaches like repetitive transcranial magnetic stimulation (rTMS) are of high interest in situations where reorganization of neural networks can be observed, e.g., after stroke. However, an increasing number of studies suggest that improvements in motor performance of the stroke-affected hand following modulation of primary motor cortex (M1) excitability by rTMS shows a high interindividual variability. We here tested the hypothesis that in stroke patients the interindividual variability of behavioral response to excitatory rTMS is related to interindividual differences in network connectivity of the stimulated region. Chronic stroke patients ( n  = 14) and healthy controls ( n  = 12) were scanned with functional magnetic resonance imaging (fMRI) while performing a simple hand motor task. Dynamic causal modeling (DCM) was used to investigate effective connectivity of key motor regions. On two different days after the fMRI experiment, patients received either intermittent theta-burst stimulation (iTBS) over ipsilesional M1 or control stimulation over the parieto-occipital cortex. Motor performance and TMS parameters of cortical excitability were measured before and after iTBS. Our results revealed that patients with better motor performance of the affected hand showed stronger endogenous coupling between supplemental motor area (SMA) and M1 before starting the iTBS intervention. Applying iTBS to ipsilesional M1 significantly increased ipsilesional M1 excitability and decreased contralesional M1 excitability as compared to control stimulation. Individual behavioral improvements following iTBS specifically correlated with neural coupling strengths in the stimulated hemisphere prior to stimulation, especially for connections targeting the stimulated M1. Combining endogenous connectivity and behavioral parameters explained 82% of the variance in hand motor performance observed after iTBS. In conclusion, the data suggest that the

θ-burst stimulation of the cerebellum interferes with internal representations of sensory-motor information related to eye movements in humans.

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Colnaghi, Silvia; Ramat, Stefano; D'Angelo, Egidio; Cortese, Andrea; Beltrami, Giorgio; Moglia, Arrigo; Versino, Maurizio

2011-12-01

Continuous theta-burst stimulation (cTBS) applied over the cerebellum exerts long-lasting effects by modulating long-term synaptic plasticity, which is thought to be the basis of learning and behavioral adaptation. To investigate the impact of cTBS over the cerebellum on short-term sensory-motor memory, we recorded in two groups of eight healthy subject each the visually guided saccades (VGSs), the memory-guided saccades (MGSs), and the multiple memory-guided saccades (MMGSs), before and after cTBS (cTBS group) or simulated cTBS (control group). In the cTBS group, cTBS determined hypometria of contralateral centrifugal VGSs and worsened the accuracy of MMGS bilaterally. In the control group, no significant differences were found between the two recording sessions. These results indicate that cTBS over the cerebellum causes eye movement effects that last longer than the stimulus duration. The VGS contralateral hypometria suggested that we eventually inhibited the fastigial nucleus on the stimulated side. MMGSs in normal subjects have a better final accuracy with respect to MGSs. Such improvement is due to the availability in MMGSs of the efference copy of the initial reflexive saccade directed toward the same peripheral target, which provides a sensory-motor information that is memorized and then used to improve the accuracy of the subsequent volitional memory-guided saccade. Thus, we hypothesize that cTBS disrupted the capability of the cerebellum to make an internal representation of the memorized sensory-motor information to be used after a short interval for forward control of saccades.

Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability

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Jimenez, Samuel; Mordillo-Mateos, Laura; Dileone, Michele

2018-01-01

obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short......Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS....... In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H...

Intermittent Theta-Burst Stimulation of the Lateral Cerebellum Increases Functional Connectivity of the Default Network

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Farzan, Faranak; Eldaief, Mark C.; Schmahmann, Jeremy D.; Pascual-Leone, Alvaro

2014-01-01

Cerebral cortical intrinsic connectivity networks share topographically arranged functional connectivity with the cerebellum. However, the contribution of cerebellar nodes to distributed network organization and function remains poorly understood. In humans, we applied theta-burst transcranial magnetic stimulation, guided by subject-specific connectivity, to regions of the cerebellum to evaluate the functional relevance of connections between cerebellar and cerebral cortical nodes in different networks. We demonstrate that changing activity in the human lateral cerebellar Crus I/II modulates the cerebral default mode network, whereas vermal lobule VII stimulation influences the cerebral dorsal attention system. These results provide novel insights into the distributed, but anatomically specific, modulatory impact of cerebellar effects on large-scale neural network function. PMID:25186750

Interindividual differences in motor network connectivity and behavioral response to iTBS in stroke patients

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Svenja Diekhoff-Krebs

2017-01-01

Full Text Available Cerebral plasticity-inducing approaches like repetitive transcranial magnetic stimulation (rTMS are of high interest in situations where reorganization of neural networks can be observed, e.g., after stroke. However, an increasing number of studies suggest that improvements in motor performance of the stroke-affected hand following modulation of primary motor cortex (M1 excitability by rTMS shows a high interindividual variability. We here tested the hypothesis that in stroke patients the interindividual variability of behavioral response to excitatory rTMS is related to interindividual differences in network connectivity of the stimulated region. Chronic stroke patients (n = 14 and healthy controls (n = 12 were scanned with functional magnetic resonance imaging (fMRI while performing a simple hand motor task. Dynamic causal modeling (DCM was used to investigate effective connectivity of key motor regions. On two different days after the fMRI experiment, patients received either intermittent theta-burst stimulation (iTBS over ipsilesional M1 or control stimulation over the parieto-occipital cortex. Motor performance and TMS parameters of cortical excitability were measured before and after iTBS. Our results revealed that patients with better motor performance of the affected hand showed stronger endogenous coupling between supplemental motor area (SMA and M1 before starting the iTBS intervention. Applying iTBS to ipsilesional M1 significantly increased ipsilesional M1 excitability and decreased contralesional M1 excitability as compared to control stimulation. Individual behavioral improvements following iTBS specifically correlated with neural coupling strengths in the stimulated hemisphere prior to stimulation, especially for connections targeting the stimulated M1. Combining endogenous connectivity and behavioral parameters explained 82% of the variance in hand motor performance observed after iTBS. In conclusion, the data suggest that

High-intensity Aerobic Exercise Blocks the Facilitation of iTBS-induced Plasticity in the Human Motor Cortex.

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Smith, Ashleigh E; Goldsworthy, Mitchell R; Wood, Fiona M; Olds, Timothy S; Garside, Tessa; Ridding, Michael C

2018-03-01

Acute exercise studies using transcranial magnetic stimulation (TMS) can provide important insights into the mechanisms underpinning the positive relationship between regular engagement in physical activity and cortical neuroplasticity. Emerging evidence indicates that a single session of aerobic exercise can promote the response to an experimentally induced suppressive neuroplasticity paradigm; however, little is known about the neuroplasticity response to facilitatory paradigms, including intermittent theta burst stimulation (iTBS). To more fully characterize the effects of exercise on brain plasticity we investigated if a single 30 min bout of high-intensity cycling (80% predicted heart rate reserve) modulated the response to an iTBS paradigm compared to rest. In 18 participants (9 females; 25.5 ± 5.0 years, range: 18-35 years) iTBS was applied using standard repetitive transcranial magnetic stimulation techniques immediately following exercise or 30 min of rest. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle at baseline, after the exercise/rest period but before iTBS, and at 5 time points following iTBS (0, 5, 10, 20 and 30 min). Contrary to our hypothesis, MEPs were suppressed following iTBS after a single 30 min bout of lower limb aerobic exercise compared to rest. These results indicate that acute aerobic exercise may not always enhance the response to an experimentally induced neuroplasticity paradigm. Further investigation of the factors that influence the relationship between exercise and neuroplasticity is warranted. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases.

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Miller, Jonathan P; Sweet, Jennifer A; Bailey, Christopher M; Munyon, Charles N; Luders, Hans O; Fastenau, Philip S

2015-07-01

Memory loss after brain injury can be a source of considerable morbidity, but there are presently few therapeutic options for restoring memory function. We have previously demonstrated that burst stimulation of the fornix is able to significantly improve memory in a rodent model of traumatic brain injury. The present study is a preliminary investigation with a small group of cases to explore whether theta burst stimulation of the fornix might improve memory in humans. Four individuals undergoing stereo-electroencephalography evaluation for drug-resistant epilepsy were enrolled. All participants were implanted with an electrode into the proximal fornix and dorsal hippocampal commissure on the language dominant (n = 3) or language non-dominant (n = 1) side, and stimulation of this electrode reliably produced a diffuse evoked potential in the head and body of the ipsilateral hippocampus. Each participant underwent testing of verbal memory (Rey Auditory-Verbal Learning Test), visual-spatial memory (Medical College of Georgia Complex Figure Test), and visual confrontational naming (Boston Naming Test Short Form) once per day over at least two consecutive days using novel test forms each day. For 50% of the trials, the fornix electrode was continuously stimulated using a burst pattern (200 Hz in 100 ms trains, five trains per second, 100 µs, 7 mA) and was compared with sham stimulation. Participants and examiners were blinded to whether stimulation was active or not, and the order of stimulation was randomized. The small sample size precluded use of inferential statistics; therefore, data were analysed using descriptive statistics and graphic analysis. Burst stimulation of the fornix was not perceived by any of the participants but was associated with a robust reversible improvement in immediate and delayed performance on the Medical College of Georgia Complex Figure Test. There were no apparent differences on either Rey Auditory-Verbal Learning Test or Boston Naming

Daily iTBS worsens hand motor training--a combined TMS, fMRI and mirror training study.

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Läppchen, C H; Ringer, T; Blessin, J; Schulz, K; Seidel, G; Lange, R; Hamzei, F

2015-02-15

Repetitive transcranial magnetic stimulation (rTMS) is used to increase regional excitability to improve motor function in combination with training after neurological diseases or events such as stroke. We investigated whether a daily application of intermittent theta burst stimulation (iTBS; a short-duration rTMS that increases regional excitability) improves the training effect compared with sham stimulation in association with a four-day hand training program using a mirror (mirror training, MT). The right dorsal premotor cortex (dPMC right) was chosen as the target region for iTBS because this region has recently been emphasized as a node within a network related to MT. Healthy subjects were randomized into the iTBS group or sham group (control group CG). In the iTBS group, iTBS was applied daily over dPMC right, which was functionally determined in an initial fMRI session prior to starting MT. MT involved 20 min of hand training daily in a mirror over four days. The hand tests, the intracortical excitability and fMRI were evaluated prior to and at the end of MT. The results of the hand training tests of the iTBS group were surprisingly significantly poorer compared with those from the CG group. Both groups showed a different course of excitability in both M1 and a different course of fMRI activation within the supplementary motor area and M1 left. We suggest the inter-regional functional balance was affected by daily iTBS over dPMC right. Maybe an inter-regional connectivity within a network is differentially balanced. An excitability increase within an inhibitory-balanced network would therefore disturb the underlying network. Copyright © 2014 Elsevier Inc. All rights reserved.

Reproducibility of Single-Pulse, Paired-Pulse, and Intermittent Theta-Burst TMS Measures in Healthy Aging, Type-2 Diabetes, and Alzheimer’s Disease

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Peter J. Fried

2017-08-01

Full Text Available Background: Transcranial magnetic stimulation (TMS can be used to assess neurophysiology and the mechanisms of cortical brain plasticity in humans in vivo. As the use of these measures in specific populations (e.g., Alzheimer’s disease; AD increases, it is critical to understand their reproducibility (i.e., test–retest reliability in the populations of interest.Objective: Reproducibility of TMS measures was evaluated in older adults, including healthy, AD, and Type-2 diabetes mellitus (T2DM groups.Methods: Participants received two identical neurophysiological assessments within a year including motor thresholds, baseline motor evoked potentials (MEPs, short- and long-interval intracortical inhibition (SICI, LICI and intracortical facilitation (ICF, and MEP changes following intermittent theta-burst stimulation (iTBS. Cronbach’s α coefficients were calculated to assess reproducibility. Multiple linear regression analyses were used to investigate factors related to intraindividual variability.Results: Reproducibility was highest for motor thresholds, followed by baseline MEPs, SICI and LICI, and was lowest for ICF and iTBS aftereffects. The AD group tended to show higher reproducibility than T2DM or controls. Intraindividual variability of baseline MEPs was related to age and variability of RMT, while the intraindividual variability in post-iTBS measures was related to baseline MEP variability, intervisit duration, and Brain-derived neurotrophic factor (BDNF polymorphism.Conclusion: Increased reproducibility in AD may reflect pathophysiological declines in the efficacy of neuroplastic mechanisms. Reproducibility of iTBS aftereffects can be improved by keeping baseline MEPs consistent, controlling for BDNF genotype, and waiting at least a week between visits.Significance: These findings provide the first direct assessment of reproducibility of TMS measures in older clinical populations. Reproducibility coefficients may be used to adjust

LTP in Hippocampal Area CA1 Is Induced by Burst Stimulation over a Broad Frequency Range Centered around Delta

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Grover, Lawrence M.; Kim, Eunyoung; Cooke, Jennifer D.; Holmes, William R.

2009-01-01

Long-term potentiation (LTP) is typically studied using either continuous high-frequency stimulation or theta burst stimulation. Previous studies emphasized the physiological relevance of theta frequency; however, synchronized hippocampal activity occurs over a broader frequency range. We therefore tested burst stimulation at intervals from 100…

Effects of inhibitory theta burst TMS to different brain sites involved in visuospatial attention - a combined neuronavigated cTBS and behavioural study.

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Platz, Thomas; Schüttauf, Johannes; Aschenbach, Julia; Mengdehl, Christine; Lotze, Martin

2016-01-01

The study sought to alter visual spatial attention in young healthy subjects by a neuronavigated inhibitory rTMS protocol (cTBS-600) to right brain areas thought to be involved in visual attentional processes, i.e. the temporoparietal junction (TPJ) and the posterior middle frontal gyrus (pMFG), and to test the reversibility of effects by an additional consecutive cTBS to the homologue left brain cortical areas. Healthy subjects showed a leftward bias of the egocentric perspective for both visual-perceptive and visual-exploratory tasks specifically for items presented in the left hemifield. cTBS to the right TPJ, and less systematically to the right pMFG reduced this bias for visuo-spatial and exploratory visuo-motor behaviour. Further, a consecutive cTBS to the left TPJ changed the bias again towards the left for a visual-perceptive task. The evidence supports the notion of an involvement of the right TPJ (and pMFG) in spatial visual attention. The observations further indicate that inhibitory non-invasive brain stimulation (cTBS) to the left TPJ has a potential for reversing a rightward bias of spatial attention when the right TPJ is dysfunctional. Accordingly, the findings could have implications for therapeutic rTMS development for right brain damaged patients with visual neglect.

Inter-subject and Inter-session Variability of Plasticity Induction by Non-invasive Brain Stimulation

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Ziemann, Ulf; Siebner, Hartwig R

2015-01-01

in human cortex well beyond the time of stimulation. These aftereffects have been termed long-term potentiation (LTP)-like and long-term depression (LTD)-like plasticity because indirect evidence supported the notion that synaptic strengthening or weakening similar to LTP/D at the cellular level underlies......Non-invasive brain stimulation (NIBS) protocols such as regular repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), paired associative stimulation (PAS) and transcranial direct current stimulation (tDCS) can change the excitability of the stimulated neuronal network...

iTBS-induced LTP-like plasticity parallels oscillatory activity changes in the primary sensory and motor areas of macaque monkeys.

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Papazachariadis, Odysseas; Dante, Vittorio; Verschure, Paul F M J; Del Giudice, Paolo; Ferraina, Stefano

2014-01-01

Recently, neuromodulation techniques based on the use of repetitive transcranial magnetic stimulation (rTMS) have been proposed as a non-invasive and efficient method to induce in vivo long-term potentiation (LTP)-like aftereffects. However, the exact impact of rTMS-induced perturbations on the dynamics of neuronal population activity is not well understood. Here, in two monkeys, we examine changes in the oscillatory activity of the sensorimotor cortex following an intermittent theta burst stimulation (iTBS) protocol. We first probed iTBS modulatory effects by testing the iTBS-induced facilitation of somatosensory evoked potentials (SEP). Then, we examined the frequency information of the electrocorticographic signal, obtained using a custom-made miniaturised multi-electrode array for electrocorticography, after real or sham iTBS. We observed that iTBS induced facilitation of SEPs and influenced spectral components of the signal, in both animals. The latter effect was more prominent on the θ band (4-8 Hz) and the high γ band (55-90 Hz), de-potentiated and potentiated respectively. We additionally found that the multi-electrode array uniformity of β (13-26 Hz) and high γ bands were also afflicted by iTBS. Our study suggests that enhanced cortical excitability promoted by iTBS parallels a dynamic reorganisation of the interested neural network. The effect in the γ band suggests a transient local modulation, possibly at the level of synaptic strength in interneurons. The effect in the θ band suggests the disruption of temporal coordination on larger spatial scales.

iTBS-induced LTP-like plasticity parallels oscillatory activity changes in the primary sensory and motor areas of macaque monkeys.

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Odysseas Papazachariadis

Full Text Available Recently, neuromodulation techniques based on the use of repetitive transcranial magnetic stimulation (rTMS have been proposed as a non-invasive and efficient method to induce in vivo long-term potentiation (LTP-like aftereffects. However, the exact impact of rTMS-induced perturbations on the dynamics of neuronal population activity is not well understood. Here, in two monkeys, we examine changes in the oscillatory activity of the sensorimotor cortex following an intermittent theta burst stimulation (iTBS protocol. We first probed iTBS modulatory effects by testing the iTBS-induced facilitation of somatosensory evoked potentials (SEP. Then, we examined the frequency information of the electrocorticographic signal, obtained using a custom-made miniaturised multi-electrode array for electrocorticography, after real or sham iTBS. We observed that iTBS induced facilitation of SEPs and influenced spectral components of the signal, in both animals. The latter effect was more prominent on the θ band (4-8 Hz and the high γ band (55-90 Hz, de-potentiated and potentiated respectively. We additionally found that the multi-electrode array uniformity of β (13-26 Hz and high γ bands were also afflicted by iTBS. Our study suggests that enhanced cortical excitability promoted by iTBS parallels a dynamic reorganisation of the interested neural network. The effect in the γ band suggests a transient local modulation, possibly at the level of synaptic strength in interneurons. The effect in the θ band suggests the disruption of temporal coordination on larger spatial scales.

Reduced multimodal integration of memory features following continuous theta burst stimulation of angular gyrus.

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Yazar, Yasemin; Bergström, Zara M; Simons, Jon S

Lesions of the angular gyrus (AnG) region of human parietal cortex do not cause amnesia, but appear to be associated with reduction in the ability to consciously experience the reliving of previous events. We used continuous theta burst stimulation to test the hypothesis that the cognitive mechanism implicated in this memory deficit might be the integration of retrieved sensory event features into a coherent multimodal memory representation. Healthy volunteers received stimulation to AnG or a vertex control site after studying stimuli that each comprised a visual object embedded in a scene, with the name of the object presented auditorily. Participants were then asked to make memory judgments about the studied stimuli that involved recollection of single event features (visual or auditory), or required integration of event features within the same modality, or across modalities. Participants' ability to retrieve context features from across multiple modalities was significantly reduced after AnG stimulation compared to stimulation of the vertex. This effect was observed only for the integration of cross-modal context features but not for integration of features within the same modality, and could not be accounted for by task difficulty as performance was matched across integration conditions following vertex stimulation. These results support the hypothesis that AnG is necessary for the multimodal integration of distributed cortical episodic features into a unified conscious representation that enables the experience of remembering. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Excitatory stimulation of the right inferior parietal cortex lessens implicit religiousness/spirituality.

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Crescentini, Cristiano; Di Bucchianico, Marilena; Fabbro, Franco; Urgesi, Cosimo

2015-04-01

Although religiousness and spirituality (RS) are considered two fundamental constituents of human life, neuroscientific investigation has long avoided the study of their neurocognitive basis. Nevertheless, recent investigations with brain imaging and brain damaged patients, and more recently with brain stimulation methods, have documented important associations between RS beliefs and experiences and frontoparietal neural activity. In this study, we further investigated how individuals' implicit RS self-representations can be modulated by changes in right inferior parietal lobe (IPL) excitability, a key region associated to RS. To this end, we combined continuous theta burst stimulation (cTBS), intermittent TBS (iTBS), and sham TBS with RS-related, Implicit Association Test (IAT) and with a control self-esteem (SE) IAT in a group of fourteen healthy adult individuals. A specific decrease of implicit RS, as measured with the IAT effect, was induced by increasing IPL excitability with iTBS; conversely cTBS, which is supposedly inhibitory, left participants' implicit RS unchanged. The performance in the control SE-IAT was left unchanged by any TBS stimulation. These data showed the causative role of right IPL functional state in mediating plastic changes of implicit RS. Implications of these results are also discussed in the light of the variability of behavioral effects associated with TBS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transcranial magnetic stimulation primes the effects of exercise therapy in multiple sclerosis.

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Mori, Francesco; Ljoka, Concetta; Magni, Elisabetta; Codecà, Claudia; Kusayanagi, Hajime; Monteleone, Fabrizia; Sancesario, Andrea; Bernardi, Giorgio; Koch, Giacomo; Foti, Calogero; Centonze, Diego

2011-07-01

Exercise therapy (ET) can be beneficial in disabled multiple sclerosis (MS) patients. Intermittent transcranial magnetic theta burst stimulation (iTBS) induces long-term excitability changes of the cerebral cortex and may ameliorate spasticity in MS. We investigated whether the combination of iTBS and a program of ET can improve motor disability in MS patients. In a double-blind, sham-controlled trial, 30 participants were randomized to three different interventions: iTBS plus ET, sham stimulation plus ET, and iTBS alone. Before and after 2 weeks of treatment, measures of spasticity through the modified Ashworth scale (MAS) and the 88 items Multiple Sclerosis Spasticity Score questionnaire (MSSS-88), fatigue through the Fatigue Severity Scale (FSS), daily living activities (ADL) through the Barthel index and health-related quality of life (HRQoL) through the 54 items Multiple Sclerosis Quality of life inventory (MSQoL-54) were collected. iTBS plus ET reduced MAS, MSSS-88, FSS scores, while in the Barthel index and MSQoL-54, physical composite scores were increased. iTBS alone caused a reduction of the MAS score, while none of the measured scales showed significant changes after sham iTBS plus ET. iTBS associated with ET is a promising tool for motor rehabilitation of MS patients.

Time-course of changes in neuronal activity markers following iTBS-TMS of the rat neocortex.

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Hoppenrath, Kathrin; Funke, Klaus

2013-03-01

In a rat model of transcranial magnetic stimulation we could recently show that intermittent theta-burst stimulation (iTBS) affects the neocortical expression of the immediate early gene products c-Fos and zif268 as well as that of the two glutamic acid decarboxylase isoforms GAD65 and GAD67 and that of the calcium-binding proteins calbindin (CB) and parvalbumin (PV), known as markers of excitatory and inhibitory activity. We now analyzed in more detail the time course of changes in the expression of these proteins at 10, 20, 40, 80 and 160min following a single block of iTBS consisting of 600 stimuli. Initial increase in c-Fos, zif268 and GAD65 (20min) signals transient activation of excitatory and inhibitory neurons, thereafter first followed by a decrease in markers of activity of inhibitory neurons (GAD67, PV, CB: 20-80min) and then by a late decrease in c-Fos and GAD65 expression (160min). The results demonstrate that one iTBS block may have an after-effect of at least two different phases, an early phase with increased neuronal activity (c-Fos, zif268) but also the likelihood of increased GABA-release (GAD65), followed by a late phase (>40min) of reduced neuronal activity in excitatory and inhibitory systems which may indicate a state of reduced excitability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparative study of ipsilesional and contralesional repetitive transcranial magnetic stimulations for acute infarction.

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Watanabe, Kosuke; Kudo, Yosuke; Sugawara, Eriko; Nakamizo, Tomoki; Amari, Kazumitsu; Takahashi, Koji; Tanaka, Osamu; Endo, Miho; Hayakawa, Yuko; Johkura, Ken

2018-01-15

Repetitive transcranial magnetic stimulation (rTMS) is reported to improve chronic post-stoke hemiparesis. However, application of rTMS during the acute phase of post-stroke has not fully been investigated. We investigated the safety and the efficacy of intermittent theta-burst stimulation (iTBS) of the affected motor cortex and 1-Hz stimulation of the unaffected hemisphere during the acute phase in patients with hemiparesis due to capsular infarction. Twenty one patients who met the study criteria were randomly assigned to receive, starting within 7days after stroke onset and for a period of 10days, iTBS of the affected motor cortex hand area (n=8), 1-Hz stimulation of the unaffected motor cortex hand area (n=7), or sham stimulation (n=6). Upper limb motor function was evaluated before rTMS and 12weeks after onset of the stroke. Evaluation was based on the Fugl-Meyer Assessment (FMA), Stroke Impairment Assessment Set (SIAS), Modified Ashworth Scale (MAS), grip strength, and motor evoked potential (MEP) amplitude in the first dorsal interosseous (FDI) muscle. Both iTBS applied to the affected motor cortex hand area and 1-Hz stimulation applied to the unaffected motor cortex hand area enhanced motor recovery. In comparison to sham stimulation, iTBS increased the SIAS finger-function test score, and 1-Hz stimulation decreased the MAS wrist and finger score. Ipsilesional iTBS and contralesional 1-Hz stimulation applied during the acute phase of stroke have different effects: ipsilesional iTBS improves movement of the affected limb, whereas contralesional 1-Hz stimulation reduces spasticity of the affected limb. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of chronic iTBS-rTMS and enriched environment on visual cortex early critical period and visual pattern discrimination in dark-reared rats.

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Castillo-Padilla, Diana V; Funke, Klaus

2016-01-01

Early cortical critical period resembles a state of enhanced neuronal plasticity enabling the establishment of specific neuronal connections during first sensory experience. Visual performance with regard to pattern discrimination is impaired if the cortex is deprived from visual input during the critical period. We wondered how unspecific activation of the visual cortex before closure of the critical period using repetitive transcranial magnetic stimulation (rTMS) could affect the critical period and the visual performance of the experimental animals. Would it cause premature closure of the plastic state and thus worsen experience-dependent visual performance, or would it be able to preserve plasticity? Effects of intermittent theta-burst stimulation (iTBS) were compared with those of an enriched environment (EE) during dark-rearing (DR) from birth. Rats dark-reared in a standard cage showed poor improvement in a visual pattern discrimination task, while rats housed in EE or treated with iTBS showed a performance indistinguishable from rats reared in normal light/dark cycle. The behavioral effects were accompanied by correlated changes in the expression of brain-derived neurotrophic factor (BDNF) and atypical PKC (PKCζ/PKMζ), two factors controlling stabilization of synaptic potentiation. It appears that not only nonvisual sensory activity and exercise but also cortical activation induced by rTMS has the potential to alleviate the effects of DR on cortical development, most likely due to stimulation of BDNF synthesis and release. As we showed previously, iTBS reduced the expression of parvalbumin in inhibitory cortical interneurons, indicating that modulation of the activity of fast-spiking interneurons contributes to the observed effects of iTBS. © 2015 Wiley Periodicals, Inc.

Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

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Claudia Mastroeni

Full Text Available Repetitive transcranial magnetic stimulation (rTMS of the human motor hand area (M1HAND can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66met polymorphism in the brain-derived neurotrophic factor (BDNF gene. Here we used theta burst stimulation (TBS to examine whether the BDNF val(66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS usually inducing a lasting increase and continuous TBS (cTBS a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66met (n = 12 and val(66val (n = 17 carriers received neuronavigated cTBS followed by cTBS (n = 27, cTBS followed by iTBS (n = 29, and iTBS followed by iTBS (n = 28. Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS and increase (iTBS in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66met carriers and val(66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66met polymorphism, our results do not support the notion that the BDNF val(66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

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Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

2013-01-01

Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

Differential Effects of HRAS Mutation on LTP-Like Activity Induced by Different Protocols of Repetitive Transcranial Magnetic Stimulation.

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Dileone, Michele; Ranieri, Federico; Florio, Lucia; Capone, Fioravante; Musumeci, Gabriella; Leoni, Chiara; Mordillo-Mateos, Laura; Tartaglia, Marco; Zampino, Giuseppe; Di Lazzaro, Vincenzo

2016-01-01

Costello syndrome (CS) is a rare congenital disorder due to a G12S amino acid substitution in HRAS protoncogene. Previous studies have shown that Paired Associative Stimulation (PAS), a repetitive brain stimulation protocol inducing motor cortex plasticity by coupling peripheral nerve stimulation with brain stimulation, leads to an extremely pronounced motor cortex excitability increase in CS patients. Intermittent Theta Burst Stimulation (iTBS) represents a protocol able to induce motor cortex plasticity by trains of stimuli at 50 Hz. In healthy subjects PAS and iTBS produce similar after-effects in motor cortex excitability. Experimental models showed that HRAS-dependent signalling pathways differently affect LTP induced by different patterns of repetitive synaptic stimulation. We aimed to compare iTBS-induced after-effects on motor cortex excitability with those produced by PAS in CS patients and to observe whether HRAS mutation differentially affects two different forms of neuromodulation protocols. We evaluated in vivo after-effects induced by PAS and iTBS applied over the right motor cortex in 4 CS patients and in 21 healthy age-matched controls. Our findings confirmed HRAS-dependent extremely pronounced PAS-induced after-effects and showed for the first time that iTBS induces no change in MEP amplitude in CS patients whereas both protocols lead to an increase of about 50% in controls. CS patients are characterized by an impairment of iTBS-related LTP-like phenomena besides enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling pathways have a differential influence on PAS- and iTBS-induced plasticity in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain-Derived Neurotrophic Factor – A Major Player in Stimulation-Induced Homeostatic Metaplasticity of Human Motor Cortex?

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Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

2013-01-01

Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val66met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val66met (n = 12) and val66val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val66met carriers and val66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val66met polymorphism, our results do not support the notion that the BDNF val66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND. PMID:23469118

Network connectivity and individual responses to brain stimulation in the human motor system.

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Cárdenas-Morales, Lizbeth; Volz, Lukas J; Michely, Jochen; Rehme, Anne K; Pool, Eva-Maria; Nettekoven, Charlotte; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2014-07-01

The mechanisms driving cortical plasticity in response to brain stimulation are still incompletely understood. We here explored whether neural activity and connectivity in the motor system relate to the magnitude of cortical plasticity induced by repetitive transcranial magnetic stimulation (rTMS). Twelve right-handed volunteers underwent functional magnetic resonance imaging during rest and while performing a simple hand motor task. Resting-state functional connectivity, task-induced activation, and task-related effective connectivity were assessed for a network of key motor areas. We then investigated the effects of intermittent theta-burst stimulation (iTBS) on motor-evoked potentials (MEP) for up to 25 min after stimulation over left primary motor cortex (M1) or parieto-occipital vertex (for control). ITBS-induced increases in MEP amplitudes correlated negatively with movement-related fMRI activity in left M1. Control iTBS had no effect on M1 excitability. Subjects with better response to M1-iTBS featured stronger preinterventional effective connectivity between left premotor areas and left M1. In contrast, resting-state connectivity did not predict iTBS aftereffects. Plasticity-related changes in M1 following brain stimulation seem to depend not only on local factors but also on interconnected brain regions. Predominantly activity-dependent properties of the cortical motor system are indicative of excitability changes following induction of cortical plasticity with rTMS. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Motor Cortex Stimulation Reverses Maladaptive Plasticity Following Spinal Cord Injury

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2011-09-01

burst stimulation (TBS) protocols can produce powerful effects on motor cortex outputs, with intermittent TBS ( iTBS ) being most effective [27... iTBS (2-second trains of TBS repeated every 10 seconds) appeared to increase mechanical withdrawal thresholds on the hind paw ipsilateral to the

Sniff-Like Patterned Input Results in Long-Term Plasticity at the Rat Olfactory Bulb Mitral and Tufted Cell to Granule Cell Synapse

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Mahua Chatterjee

2016-01-01

Full Text Available During odor sensing the activity of principal neurons of the mammalian olfactory bulb, the mitral and tufted cells (MTCs, occurs in repetitive bursts that are synchronized to respiration, reminiscent of hippocampal theta-gamma coupling. Axonless granule cells (GCs mediate self- and lateral inhibitory interactions between the excitatory MTCs via reciprocal dendrodendritic synapses. We have explored long-term plasticity at this synapse by using a theta burst stimulation (TBS protocol and variations thereof. GCs were excited via glomerular stimulation in acute brain slices. We find that TBS induces exclusively long-term depression in the majority of experiments, whereas single bursts (“single-sniff paradigm” can elicit both long-term potentiation and depression. Statistical analysis predicts that the mechanism underlying this bidirectional plasticity involves the proportional addition or removal of presynaptic release sites. Gamma stimulation with the same number of APs as in TBS was less efficient in inducing plasticity. Both TBS- and “single-sniff paradigm”-induced plasticity depend on NMDA receptor activation. Since the onset of plasticity is very rapid and requires little extra activity, we propose that these forms of plasticity might play a role already during an ongoing search for odor sources. Our results imply that components of both short-term and long-term olfactory memory may be encoded at this synapse.

Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations : Negative Findings From a Double-Blind-Randomized Trial

NARCIS (Netherlands)

Koops, Sanne; van Dellen, Edwin; Schutte, Maya J L; Nieuwdorp, Wendy; Neggers, Sebastiaan F W; Sommer, Iris E C

BACKGROUND: Auditory verbal hallucinations (AVH) in schizophrenia are resistant to antipsychotic medication in approximately 25% of patients. Treatment with repetitive transcranial magnetic stimulation (rTMS) for refractory AVH has shown varying results. A stimulation protocol using continuous theta

Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia.

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Deppermann, S; Notzon, S; Kroczek, A; Rosenbaum, D; Haeussinger, F B; Diemer, J; Domschke, K; Fallgatter, A J; Ehlis, A-C; Zwanzger, P

2016-07-01

A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further. Copyright © 2016 Elsevier B.V. All rights reserved.

Artificial theta stimulation impairs encoding of contextual fear memory.

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Arto Lipponen

Full Text Available Several experiments have demonstrated an intimate relationship between hippocampal theta rhythm (4-12 Hz and memory. Lesioning the medial septum or fimbria-fornix, a fiber track connecting the hippocampus and the medial septum, abolishes the theta rhythm and results in a severe impairment in declarative memory. To assess whether there is a causal relationship between hippocampal theta and memory formation we investigated whether restoration of hippocampal theta by electrical stimulation during the encoding phase also restores fimbria-fornix lesion induced memory deficit in rats in the fear conditioning paradigm. Male Wistar rats underwent sham or fimbria-fornix lesion operation. Stimulation electrodes were implanted in the ventral hippocampal commissure and recording electrodes in the septal hippocampus. Artificial theta stimulation of 8 Hz was delivered during 3-min free exploration of the test cage in half of the rats before aversive conditioning with three foot shocks during 2 min. Memory was assessed by total freezing time in the same environment 24 h and 28 h after fear conditioning, and in an intervening test session in a different context. As expected, fimbria-fornix lesion impaired fear memory and dramatically attenuated hippocampal theta power. Artificial theta stimulation produced continuous theta oscillations that were almost similar to endogenous theta rhythm in amplitude and frequency. However, contrary to our predictions, artificial theta stimulation impaired conditioned fear response in both sham and fimbria-fornix lesioned animals. These data suggest that restoration of theta oscillation per se is not sufficient to support memory encoding after fimbria-fornix lesion and that universal theta oscillation in the hippocampus with a fixed frequency may actually impair memory.

Prefrontal θ-Burst Stimulation Disrupts the Organizing Influence of Active Short-Term Retrieval on Episodic Memory.

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Marin, Bianca M; VanHaerents, Stephen A; Voss, Joel L; Bridge, Donna J

2018-01-01

Dorsolateral prefrontal cortex (DLPFC) is thought to organize items in working memory and this organizational role may also influence long-term memory. To causally test this hypothesized role of DLPFC in long-term memory formation, we used θ-burst noninvasive stimulation (TBS) to modulate DLPFC involvement in a memory task that assessed the influence of active short-term retrieval on later memory. Human subjects viewed three objects on a grid and then either actively retrieved or passively restudied one object's location after a brief delay. Long-term memory for the other objects was assessed after a delay to evaluate the beneficial role of active short-term retrieval on subsequent memory for the entire set of object locations. We found that DLPFC TBS had no significant effects on short-term memory. In contrast, DLPFC TBS impaired long-term memory selectively in the active-retrieval condition but not in the passive-restudy condition. These findings are consistent with the hypothesized contribution of DLPFC to the organizational processes operative during active short-term retrieval that influence long-term memory, although other regions that were not stimulated could provide similar contributions. Notably, active-retrieval and passive-restudy conditions were intermixed, and therefore nonspecific influences of stimulation were well controlled. These results suggest that DLPFC is causally involved in organizing event information during active retrieval to support coherent long-term memory formation.

Bilateral theta-burst TMS to influence global gestalt perception.

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Bernd Ritzinger

Full Text Available While early and higher visual areas along the ventral visual pathway in the inferotemporal cortex are critical for the recognition of individual objects, the neural representation of human perception of complex global visual scenes remains under debate. Stroke patients with a selective deficit in the perception of a complex global Gestalt with intact recognition of individual objects - a deficit termed simultanagnosia - greatly helped to study this question. Interestingly, simultanagnosia typically results from bilateral lesions of the temporo-parietal junction (TPJ. The present study aimed to verify the relevance of this area for human global Gestalt perception. We applied continuous theta-burst TMS either unilaterally (left or right or bilateral simultaneously over TPJ. Healthy subjects were presented with hierarchically organized visual stimuli that allowed parametrical degrading of the object at the global level. Identification of the global Gestalt was significantly modulated only for the bilateral TPJ stimulation condition. Our results strengthen the view that global Gestalt perception in the human brain involves TPJ and is co-dependent on both hemispheres.

Long-term plasticity is proportional to theta-activity.

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Marian Tsanov

Full Text Available BACKGROUND: Theta rhythm in the hippocampal formation is a main feature of exploratory behaviour and is believed to enable the encoding of new spatial information and the modification of synaptic weights. Cyclic changes of dentate gyrus excitability during theta rhythm are related to its function, but whether theta epochs per se are able to alter network properties of dentate gyrus for long time-periods is still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We used low-frequency stimulation protocols that amplify the power of endogenous theta oscillations, in order to estimate the plasticity effect of endogenous theta oscillations on a population level. We found that stimulation-induced augmentation of the theta rhythm is linked to a subsequent increase of neuronal excitability and decrease of the synaptic response. This EPSP-to-Spike uncoupling is related to an increased postsynaptic spiking on the positive phases of theta frequency oscillations. Parallel increase of the field EPSP slope and the population spike occurs only after concurrent pre- and postsynaptic activation. Furthermore, we observed that long-term potentiation (>24 h occurs in the dentate gyrus of freely behaving adult rats after phasic activity of entorhinal afferents in the theta-frequency range. This plasticity is proportional to the field bursting activity of granule cells during the stimulation, and may comprise a key step in spatial information transfer. Long-term potentiation of the synaptic component occurs only when the afferent stimulus precedes the evoked population burst, and is input-specific. CONCLUSIONS/SIGNIFICANCE: Our data confirm the role of the dentate gyrus in filtering information to the subsequent network during the activated state of the hippocampus.

Weight-specific anticipatory coding of grip force in human dorsal premotor cortex

DEFF Research Database (Denmark)

van Nuenen, Bart F L; Kuhtz-Buschbeck, Johann; Schulz, Christian

2012-01-01

, using either continuous theta burst stimulation (cTBS) at 80% (inhibitory cTBS) or 30% (sham cTBS) of active motor threshold. The conditioning effects of cTBS on preparatory brain activity were assessed with functional MRI, while participants lifted a light or heavy weight in response to a go-cue (S2......). An additional pre-cue (S1) correctly predicted the weight in 75% of the trials. Participants were asked to use this prior information to prepare for the lift. In the sham condition, grip force showed a consistent undershoot, if the S1 incorrectly prompted the preparation of a light lift. Likewise, an S1...... during object lifting....

Oscillatory frontal theta responses are increased upon bisensory stimulation.

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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.

Continuous theta-burst stimulation to primary motor cortex reveals asymmetric compensation for sensory attenuation in bimanual repetitive force production.

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Therrien, Amanda S; Lyons, James; Balasubramaniam, Ramesh

2013-08-01

Studies of fingertip force production have shown that self-produced forces are perceived as weaker than externally generated forces. This is due to mechanisms of sensory reafference where the comparison between predicted and actual sensory feedback results in attenuated perceptions of self-generated forces. Without an external reference to calibrate attenuated performance judgments, a compensatory overproduction of force is exhibited. It remains unclear whether the force overproduction seen in the absence of visual reference stimuli differs when forces are produced bimanually. We studied performance of two versions of a bimanual sequential force production task compared with each hand performing the task unimanually. When the task goal was shared, force series produced by each hand in bimanual conditions were found to be uncorrelated. When the bimanual task required each hand to reach a target force level, we found asymmetries in the degree of force overproduction between the hands following visual feedback removal. Unilateral continuous theta-burst stimulation of the left primary motor cortex yielded a selective reduction of force overproduction in the hand contralateral to stimulation by disrupting sensory reafference processes. While variability was lower in bimanual trials when the task goal was shared, this influence of hand condition disappeared when the target force level was to be reached by each hand simultaneously. Our findings strengthen the notion that force control in bimanual action is less tightly coupled than other mechanisms of bimanual motor control and show that this effector specificity may be extended to the processing and compensation for mechanisms of sensory reafference.

Relationship Between Non-invasive Brain Stimulation-induced Plasticity and Capacity for Motor Learning.

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López-Alonso, Virginia; Cheeran, Binith; Fernández-del-Olmo, Miguel

2015-01-01

Cortical plasticity plays a key role in motor learning (ML). Non-invasive brain stimulation (NIBS) paradigms have been used to modulate plasticity in the human motor cortex in order to facilitate ML. However, little is known about the relationship between NIBS-induced plasticity over M1 and ML capacity. NIBS-induced MEP changes are related to ML capacity. 56 subjects participated in three NIBS (paired associative stimulation, anodal transcranial direct current stimulation and intermittent theta-burst stimulation), and in three lab-based ML task (serial reaction time, visuomotor adaptation and sequential visual isometric pinch task) sessions. After clustering the patterns of response to the different NIBS protocols, we compared the ML variables between the different patterns found. We used regression analysis to explore further the relationship between ML capacity and summary measures of the MEPs change. We ran correlations with the "responders" group only. We found no differences in ML variables between clusters. Greater response to NIBS protocols may be predictive of poor performance within certain blocks of the VAT. "Responders" to AtDCS and to iTBS showed significantly faster reaction times than "non-responders." However, the physiological significance of these results is uncertain. MEP changes induced in M1 by PAS, AtDCS and iTBS appear to have little, if any, association with the ML capacity tested with the SRTT, the VAT and the SVIPT. However, cortical excitability changes induced in M1 by AtDCS and iTBS may be related to reaction time and retention of newly acquired skills in certain motor learning tasks. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhancing the Temporal Complexity of Distributed Brain Networks with Patterned Cerebellar Stimulation

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Farzan, Faranak; Pascual-Leone, Alvaro; Schmahmann, Jeremy D.; Halko, Mark

2016-01-01

Growing evidence suggests that sensory, motor, cognitive and affective processes map onto specific, distributed neural networks. Cerebellar subregions are part of these networks, but how the cerebellum is involved in this wide range of brain functions remains poorly understood. It is postulated that the cerebellum contributes a basic role in brain functions, helping to shape the complexity of brain temporal dynamics. We therefore hypothesized that stimulating cerebellar nodes integrated in different networks should have the same impact on the temporal complexity of cortical signals. In healthy humans, we applied intermittent theta burst stimulation (iTBS) to the vermis lobule VII or right lateral cerebellar Crus I/II, subregions that prominently couple to the dorsal-attention/fronto-parietal and default-mode networks, respectively. Cerebellar iTBS increased the complexity of brain signals across multiple time scales in a network-specific manner identified through electroencephalography (EEG). We also demonstrated a region-specific shift in power of cortical oscillations towards higher frequencies consistent with the natural frequencies of targeted cortical areas. Our findings provide a novel mechanism and evidence by which the cerebellum contributes to multiple brain functions: specific cerebellar subregions control the temporal dynamics of the networks they are engaged in. PMID:27009405

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study.

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Lai, Chih-Jou; Wang, Chih-Pin; Tsai, Po-Yi; Chan, Rai-Chi; Lin, Shan-Hui; Lin, Fu-Gong; Hsieh, Chin-Yi

2015-01-01

To identify the effective predictors for therapeutic outcomes based on intermittent theta-burst stimulation (iTBS). A sham-controlled, double-blind parallel study design. A tertiary hospital. People with stroke (N=72) who presented with unilateral hemiplegia. Ten consecutive sessions of real or sham iTBS were implemented with the aim of enhancing hand function. Patients were categorized into 4 groups according to the presence (MEP+) or absence (MEP-) of motor-evoked potentials (MEPs) and grip strength according to the Medical Research Council (MRC) scale. Cortical excitability, Wolf Motor Function Test (WMFT), finger-tapping task (FT), and simple reaction time were performed before and after the sessions. MEPs and the MRC scale were predictive of iTBS therapeutic outcomes. Group A (MEP+, MRC>1) exhibited the greatest WMFT change (7.6±2.3, P1; 5.2±2.2 score change) and group C (MEP-, MRC=0; 2.3±1.5 score change). These improvements were correlated significantly with baseline motor function and ipsilesional maximum MEP amplitude. The effectiveness of iTBS modulation for poststroke motor enhancement depends on baseline hand grip strength and the presence of MEPs. Our findings indicate that establishing neurostimulation strategies based on the proposed electrophysiological and clinical criteria can allow iTBS to be executed with substantial precision. Effective neuromodulatory strategies can be formulated by using electrophysiological features and clinical presentation information as guidelines. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Neuropeptide Y as a possible homeostatic element for changes in cortical excitability induced by repetitive transcranial magnetic stimulation.

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Jazmati, Danny; Neubacher, Ute; Funke, Klaus

2018-02-24

Repetitive transcranial magnetic stimulation (rTMS) is able to modify cortical excitability. Rat rTMS studies revealed a modulation of inhibitory systems, in particular that of the parvalbumin-expressing (PV+) interneurons, when using intermittent theta-burst stimulation (iTBS). The potential disinhibitory action of iTBS raises the questions of how neocortical circuits stabilize excitatory-inhibitory balance within a physiological range. Neuropeptide Y (NPY) appears to be one candidate. Analysis of cortical expression of PV, NPY and vesicular glutamate transporter type 1 (vGluT1) by immunohistochemical means at the level of cell counts, mean neuropil expression and single cell pre-/postsynaptic expression, with and without intraventricular NPY-injection. Our results show that iTBS not only reduced the number of neurons with high-PV expression in a dose-dependent fashion, but also increased the cortical expression of NPY, discussed to reduce glutamatergic transmission, and this was further associated with a reduced vGluT1 expression, an indicator of glutamateric presynaptic activity. Interneurons showing a low-PV expression exhibit less presynaptic vGluT1 expression compared to those with a high-PV expression. Intraventricular application of NPY prior to iTBS prevented the iTBS-induced reduction in the number of high-PV neurons, the reduction in tissue vGluT1 level and that presynaptic to high-PV cells. We conclude that NPY, possibly via a global but also slow homeostatic control of glutamatergic transmission, modulates the strength and direction of the iTBS effects, likely preventing pathological imbalance of excitatory and inhibitory cortical activity but still allowing enough disinhibition beneficial for plastic changes as during learning. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Deleting Both PHLPP1 and CANP1 Rescues Impairments in Long-Term Potentiation and Learning in Both Single Knockout Mice

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Liu, Yan; Sun, Jiandong; Wang, Yubin; Lopez, Dulce; Tran, Jennifer; Bi, Xiaoning; Baudry, Michel

2016-01-01

Calpain-1 (CANP1) has been shown to play a critical role in synaptic plasticity and learning and memory, as its deletion in mice results in impairment in theta-burst stimulation (TBS)-induced LTP and various forms of learning and memory. Likewise, PHLPP1 (aka SCOP) has also been found to participate in learning and memory, as PHLPP1 overexpression…

A Voltage-Based STDP Rule Combined with Fast BCM-Like Metaplasticity Accounts for LTP and Concurrent "Heterosynaptic" LTD in the Dentate Gyrus In Vivo.

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Peter Jedlicka

2015-11-01

Full Text Available Long-term potentiation (LTP and long-term depression (LTD are widely accepted to be synaptic mechanisms involved in learning and memory. It remains uncertain, however, which particular activity rules are utilized by hippocampal neurons to induce LTP and LTD in behaving animals. Recent experiments in the dentate gyrus of freely moving rats revealed an unexpected pattern of LTP and LTD from high-frequency perforant path stimulation. While 400 Hz theta-burst stimulation (400-TBS and 400 Hz delta-burst stimulation (400-DBS elicited substantial LTP of the tetanized medial path input and, concurrently, LTD of the non-tetanized lateral path input, 100 Hz theta-burst stimulation (100-TBS, a normally efficient LTP protocol for in vitro preparations produced only weak LTP and concurrent LTD. Here we show in a biophysically realistic compartmental granule cell model that this pattern of results can be accounted for by a voltage-based spike-timing-dependent plasticity (STDP rule combined with a relatively fast Bienenstock-Cooper-Munro (BCM-like homeostatic metaplasticity rule, all on a background of ongoing spontaneous activity in the input fibers. Our results suggest that, at least for dentate granule cells, the interplay of STDP-BCM plasticity rules and ongoing pre- and postsynaptic background activity determines not only the degree of input-specific LTP elicited by various plasticity-inducing protocols, but also the degree of associated LTD in neighboring non-tetanized inputs, as generated by the ongoing constitutive activity at these synapses.

Comparing the Efficacy of Excitatory Transcranial Stimulation Methods Measuring Motor Evoked Potentials

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Vera Moliadze

2014-01-01

Full Text Available The common aim of transcranial stimulation methods is the induction or alterations of cortical excitability in a controlled way. Significant effects of each individual stimulation method have been published; however, conclusive direct comparisons of many of these methods are rare. The aim of the present study was to compare the efficacy of three widely applied stimulation methods inducing excitability enhancement in the motor cortex: 1 mA anodal transcranial direct current stimulation (atDCS, intermittent theta burst stimulation (iTBS, and 1 mA transcranial random noise stimulation (tRNS within one subject group. The effect of each stimulation condition was quantified by evaluating motor-evoked-potential amplitudes (MEPs in a fixed time sequence after stimulation. The analyses confirmed a significant enhancement of the M1 excitability caused by all three types of active stimulations compared to sham stimulation. There was no significant difference between the types of active stimulations, although the time course of the excitatory effects slightly differed. Among the stimulation methods, tRNS resulted in the strongest and atDCS significantly longest MEP increase compared to sham. Different time courses of the applied stimulation methods suggest different underlying mechanisms of action. Better understanding may be useful for better targeting of different transcranial stimulation techniques.

Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case-Control Pilot Study.

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Pedapati, Ernest V; Gilbert, Donald L; Erickson, Craig A; Horn, Paul S; Shaffer, Rebecca C; Wink, Logan K; Laue, Cameron S; Wu, Steve W

2016-09-01

This case-control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. We studied youth with ASD aged 11-18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing.

Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case–Control Pilot Study

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Gilbert, Donald L.; Erickson, Craig A.; Horn, Paul S.; Shaffer, Rebecca C.; Wink, Logan K.; Laue, Cameron S.; Wu, Steve W.

2016-01-01

Abstract Objective: This case–control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. Methods: We studied youth with ASD aged 11–18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. Results: Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. Conclusion: In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of

Wakefulness delta waves increase after cortical plasticity induction.

Science.gov (United States)

Assenza, G; Pellegrino, G; Tombini, M; Di Pino, G; Di Lazzaro, V

2015-06-01

Delta waves (DW) are present both during sleep and in wakefulness. In the first case, DW are considered effectors of synaptic plasticity, while in wakefulness, when they appear in the case of brain lesions, their functional meaning is not unanimously recognized. To throw light on the latter, we aimed to investigate the impact on DW exerted by the cortical plasticity-inducing protocol of intermittent theta burst stimulation (iTBS). Twenty healthy subjects underwent iTBS (11 real iTBS and nine sham iTBS) on the left primary motor cortex with the aim of inducing long-term potentiation (LTP)-like phenomena. Five-minute resting open-eye 32-channel EEG, right opponens pollicis motor-evoked potentials (MEPs), and alertness behavioral scales were collected before and up to 30 min after the iTBS. Power spectral density (PSD), interhemispheric coherence between homologous sensorimotor regions, and intrahemispheric coherence were calculated for the frequency bands ranging from delta to beta. Real iTBS induced a significant increase of both MEP amplitude and DW PSD lasting up to 30 min after stimulation, while sham iTBS did not. The DW increase was evident over frontal areas ipsilateral and close to the stimulated cortex (electrode F3). Neither real nor sham iTBS induced significant modifications in the PSD of theta, alpha, and beta bands and in the interhemispheric coherence. Behavioral visuo-analogic scales score did not demonstrate changes in alertness after stimulations. No correlations were found between MEP amplitude and PSD changes in the delta band. Our data showed that LTP induction in the motor cortex during wakefulness, by means of iTBS, is accompanied by a large and enduring increase of DW over the ipsilateral frontal cortex. The present results are strongly in favor of a prominent role of DW in the neural plasticity processes taking place during the awake state. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland

Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

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Jones, Christina B; Lulic, Tea; Bailey, Aaron Z; Mackenzie, Tanner N; Mi, Yi Qun; Tommerdahl, Mark; Nelson, Aimee J

2016-05-01

Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively. Copyright © 2016 the American Physiological Society.

Disrupting frontal eye-field activity impairs memory recall.

Science.gov (United States)

Wantz, Andrea L; Martarelli, Corinna S; Cazzoli, Dario; Kalla, Roger; Müri, René; Mast, Fred W

2016-04-13

A large body of research demonstrated that participants preferably look back to the encoding location when retrieving visual information from memory. However, the role of this 'looking back to nothing' is still debated. The goal of the present study was to extend this line of research by examining whether an important area in the cortical representation of the oculomotor system, the frontal eye field (FEF), is involved in memory retrieval. To interfere with the activity of the FEF, we used inhibitory continuous theta burst stimulation (cTBS). Before stimulation was applied, participants encoded a complex scene and performed a short-term (immediately after encoding) or long-term (after 24 h) recall task, just after cTBS over the right FEF or sham stimulation. cTBS did not affect overall performance, but stimulation and statement type (object vs. location) interacted. cTBS over the right FEF tended to impair object recall sensitivity, whereas there was no effect on location recall sensitivity. These findings suggest that the FEF is involved in retrieving object information from scene memory, supporting the hypothesis that the oculomotor system contributes to memory recall.

The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

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Milos R Ljubisavljevic

Full Text Available Although repetitive Transcranial Magnetic Stimulation (rTMS in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS and intermittent (iTBS theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS and pattern (cTBS vs. iTBS. The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss

The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS) Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury

Science.gov (United States)

Ljubisavljevic, Milos R.; Javid, Asma; Oommen, Joji; Parekh, Khatija; Nagelkerke, Nico; Shehab, Safa; Adrian, Thomas E.

2015-01-01

Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS) theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss functions. PMID

High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats

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Jing Luo

2017-02-01

Full Text Available Repetitive transcranial magnetic stimulation (rTMS has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF/tropomyosin-related kinase B (TrkB pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO, following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX, NeuN and glial fibrillary acidic protein (GFAP, and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats.

Inhibition of Pre-Supplementary Motor Area by Continuous Theta Burst Stimulation Leads to More Cautious Decision-making and More Efficient Sensory Evidence Integration.

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Tosun, Tuğçe; Berkay, Dilara; Sack, Alexander T; Çakmak, Yusuf Ö; Balcı, Fuat

2017-08-01

Decisions are made based on the integration of available evidence. The noise in evidence accumulation leads to a particular speed-accuracy tradeoff in decision-making, which can be modulated and optimized by adaptive decision threshold setting. Given the effect of pre-SMA activity on striatal excitability, we hypothesized that the inhibition of pre-SMA would lead to higher decision thresholds and an increased accuracy bias. We used offline continuous theta burst stimulation to assess the effect of transient inhibition of the right pre-SMA on the decision processes in a free-response two-alternative forced-choice task within the drift diffusion model framework. Participants became more cautious and set higher decision thresholds following right pre-SMA inhibition compared with inhibition of the control site (vertex). Increased decision thresholds were accompanied by an accuracy bias with no effects on post-error choice behavior. Participants also exhibited higher drift rates as a result of pre-SMA inhibition compared with the vertex inhibition. These results, in line with the striatal theory of speed-accuracy tradeoff, provide evidence for the functional role of pre-SMA activity in decision threshold modulation. Our results also suggest that pre-SMA might be a part of the brain network associated with the sensory evidence integration.

Increase in short-term memory capacity induced by down-regulating individual theta frequency via transcranial alternating current stimulation.

Science.gov (United States)

Vosskuhl, Johannes; Huster, René J; Herrmann, Christoph S

2015-01-01

Working memory (WM) and short-term memory (STM) supposedly rely on the phase-amplitude coupling (PAC) of neural oscillations in the theta and gamma frequency ranges. The ratio between the individually dominant gamma and theta frequencies is believed to determine an individual's memory capacity. The aim of this study was to establish a causal relationship between the gamma/theta ratio and WM/STM capacity by means of transcranial alternating current stimulation (tACS). To achieve this, tACS was delivered at a frequency below the individual theta frequency. Thereby the individual ratio of gamma to theta frequencies was changed, resulting in an increase of STM capacity. Healthy human participants (N = 33) were allocated to two groups, one receiving verum tACS, the other underwent a sham control protocol. The electroencephalogram (EEG) was measured before stimulation and analyzed with regard to the properties of PAC between theta and gamma frequencies to determine individual stimulation frequencies. After stimulation, EEG was recorded again in order to find after-effects of tACS in the oscillatory features of the EEG. Measures of STM and WM were obtained before, during and after stimulation. Frequency spectra and behavioral data were compared between groups and different measurement phases. The tACS- but not the sham stimulated group showed an increase in STM capacity during stimulation. WM was not affected in either groups. An increase in task-related theta amplitude after stimulation was observed only for the tACS group. These augmented theta amplitudes indicated that the manipulation of individual theta frequencies was successful and caused the increase in STM capacity.

Inter-individual variability in cortical excitability and motor network connectivity following multiple blocks of rTMS.

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Nettekoven, Charlotte; Volz, Lukas J; Leimbach, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2015-09-01

The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) - an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability - depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent. To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15min. We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups. Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level. Copyright © 2015 Elsevier Inc. All rights reserved.

Increase in short-term memory capacity induced by down-regulating individual theta frequency via transcranial alternating current stimulation

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Johannes eVosskuhl

2015-05-01

Full Text Available Working memory (WM and short-term memory (STM supposedly rely on the phase-amplitude coupling of neural oscillations in the theta and gamma frequency ranges. The ratio between the individually dominant gamma and theta frequencies is believed to determine an individual’s memory capacity. The aim of this study was to establish a causal relationship between the gamma/theta ratio and WM/STM capacity by means of transcranial alternating current stimulation (tACS. To achieve this, tACS was delivered at a frequency below the individual theta frequency. Thereby the individual ratio of gamma to theta frequencies was changed, resulting in an increase of STM capacity. Healthy human participants (N=33 were allocated to two groups, one receiving verum tACS, the other underwent a sham control protocol. The electroencephalogram (EEG was measured before stimulation and analyzed with regard to the properties of phase-amplitude coupling between theta and gamma frequencies to determine individual stimulation frequencies. After stimulation, EEG was recorded again in order to find after-effects of tACS in the oscillatory features of the EEG. Measures of STM and WM were obtained before, during and after stimulation. Frequency spectra and behavioral data were compared between groups and different measurement phases. The tACS- but not the sham stimulated group showed an increase in STM capacity during stimulation. WM was not affected in either groups. An increase in task-related theta amplitude after stimulation was observed only for the tACS group. These augmented theta amplitudes indicated that the manipulation of individual theta frequencies was successful and caused the increase in STM capacity.

Abnormal cortical synaptic plasticity in primary motor area in progressive supranuclear palsy.

Science.gov (United States)

Conte, Antonella; Belvisi, Daniele; Bologna, Matteo; Ottaviani, Donatella; Fabbrini, Giovanni; Colosimo, Carlo; Williams, David R; Berardelli, Alfredo

2012-03-01

No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.

Frontal and parietal theta burst TMS impairs working memory for visual-spatial conjunctions.

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Morgan, Helen M; Jackson, Margaret C; van Koningsbruggen, Martijn G; Shapiro, Kimron L; Linden, David E J

2013-03-01

In tasks that selectively probe visual or spatial working memory (WM) frontal and posterior cortical areas show a segregation, with dorsal areas preferentially involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object identity) WM. In a previous fMRI study [1], we showed that right parietal cortex (PC) was more active during WM for orientation, whereas left inferior frontal gyrus (IFG) was more active during colour WM. During WM for colour-orientation conjunctions, activity in these areas was intermediate to the level of activity for the single task preferred and non-preferred information. To examine whether these specialised areas play a critical role in coordinating visual and spatial WM to perform a conjunction task, we used theta burst transcranial magnetic stimulation (TMS) to induce a functional deficit. Compared to sham stimulation, TMS to right PC or left IFG selectively impaired WM for conjunctions but not single features. This is consistent with findings from visual search paradigms, in which frontal and parietal TMS selectively affects search for conjunctions compared to single features, and with combined TMS and functional imaging work suggesting that parietal and frontal regions are functionally coupled in tasks requiring integration of visual and spatial information. Our results thus elucidate mechanisms by which the brain coordinates spatially segregated processing streams and have implications beyond the field of working memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Manual evaluation of residual curarization using double burst stimulation

DEFF Research Database (Denmark)

Drenck, N E; Ueda, N; Olsen, Niels Vidiendal

1989-01-01

Double burst stimulation (DBS) is a new mode of stimulation developed to reveal residual neuromuscular blockade under clinical conditions. The stimulus consists of two short bursts of 50 Hz tetanic stimulation, separated by 750 ms, and the response to the stimulation is two short muscle contracti......Double burst stimulation (DBS) is a new mode of stimulation developed to reveal residual neuromuscular blockade under clinical conditions. The stimulus consists of two short bursts of 50 Hz tetanic stimulation, separated by 750 ms, and the response to the stimulation is two short muscle...... contractions. Fade in the response results from neuromuscular blockade as with train-of-four stimulation (TOF). The authors compared the sensitivity of DBS and TOF in the detection of residual neuromuscular blockade during clinical anaesthesia. Fifty-two healthy patients undergoing surgery were studied...... with DBS than with TOF, regardless of the TOF ratio level. Absence of fade with TOF implied a 48% chance of considerable residual relaxation as compared with 9% when fade was absent with DBS. The results demonstrate that DBS is more sensitive than TOF in the manual detection of residual neuromuscular...

Tell it to a child! A brain stimulation study of the role of left inferior frontal gyrus in emotion regulation during storytelling.

Science.gov (United States)

Urgesi, Cosimo; Mattiassi, Alan D A; Buiatti, Tania; Marini, Andrea

2016-08-01

In everyday life we need to continuously regulate our emotional responses according to their social context. Strategies of emotion regulation allow individuals to control time, intensity, nature and expression of emotional responses to environmental stimuli. The left inferior frontal gyrus (LIFG) is involved in the cognitive control of the selection of semantic content. We hypothesized that it might also be involved in the regulation of emotional feelings and expressions. We applied continuous theta burst stimulation (cTBS) over LIFG or a control site before a newly-developed ecological regulation task that required participants to produce storytelling of pictures with negative or neutral valence to either a peer (unregulated condition) or a child (regulated condition). Linguistic, expressive, and physiological responses were analyzed in order to assess the effects of LIFG-cTBS on emotion regulation. Results showed that the emotion regulation context modulated the emotional content of narrative productions, but not the physiologic orienting response or the early expressive behavior to negative stimuli. Furthermore, LIFG-cTBS disrupted the text-level structuring of negative picture storytelling and the early cardiac and muscular response to negative pictures; however, it did not affect the contextual emotional regulation of storytelling. These results may suggest that LIFG is involved in the initial detection of the affective arousal of emotional stimuli. Copyright © 2016 Elsevier Inc. All rights reserved.

Do studies on cortical plasticity provide a rationale for using non invasive brain stimulation as a treatment for Parkinson’s disease patients?

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Giacomo eKoch

2013-11-01

Full Text Available Animal models of Parkinson’s disease (PD have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP and long-term depression (LTD can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS and theta burst stimulation (TBS, can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential (MEP these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD-like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of levo-dopa. However, it still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms b

Bursting behaviours in cascaded stimulated Brillouin scattering

International Nuclear Information System (INIS)

Liu Zhan-Jun; He Xian-Tu; Zheng Chun-Yang; Wang Yu-Gang

2012-01-01

Stimulated Brillouin scattering is studied by numerically solving the Vlasov—Maxwell system. A cascade of stimulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma. It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light, as well as introduce a bursting behaviour in the evolution of the laser-plasma interaction. The bursting time in the reflectivity is found to be less than half the ion acoustic period. The ion temperature can affect the stimulated Brillouin scattering cascade, which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures. For stimulated Brillouin scattering saturation, higher-harmonic generation and wave—wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter. In addition, stimulated Brillouin scattering cascade can restrict the amplitude of the scattered light. (physics of gases, plasmas, and electric discharges)

Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias

NARCIS (Netherlands)

Ott, D.V.M.; Ullsperger, M.; Jocham, G.; Neumann, J.; Klein, T.A.

2011-01-01

The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of

Short-term and long-term plasticity interaction in human primary motor cortex.

Science.gov (United States)

Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Li Voti, Pietro; Bologna, Matteo; Berardelli, Alfredo

2011-05-01

Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Shaping Early Reorganization of Neural Networks Promotes Motor Function after Stroke

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Volz, L. J.; Rehme, A. K.; Michely, J.; Nettekoven, C.; Eickhoff, S. B.; Fink, G. R.; Grefkes, C.

2016-01-01

Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1–16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis. PMID:26980614

Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile X syndrome and autism spectrum disorder

Directory of Open Access Journals (Sweden)

Lindsay M Oberman

2010-06-01

Full Text Available Fragile X Syndrome (FXS is the most common heritable cause of intellectual disability. In vitro electrophysiologic data from mouse models of FXS suggest that loss of Fragile X Mental Retardation Protein (FMRP affects intracortical excitability and synaptic plasticity. Specifically, the cortex appears hyperexcitable, and use-dependent long-term potentiation (LTP and long-term depression (LTD of synaptic strength are abnormal. Though animal models provide important information, FXS and other neurodevelopmental disorders are human diseases and as such translational research to evaluate cortical excitability and plasticity must be applied in the human. Transcranial magnetic stimulation (TMS paradigms have recently been developed to noninvasively investigate cortical excitability using paired-pulse stimulation, as well as LTP- and LTD-like synaptic plasticity in response to theta burst stimulation (TBS in vivo in the human. TBS applied on consecutive days can be used to measure metaplasticity (the ability of the synapse to undergo a second plastic change following a recent induction of plasticity. The current study investigated intracortical inhibition, plasticity and metaplasticity in full mutation females with FXS, participants with autism spectrum disorders (ASD, and neurotypical controls. Results suggest that intracortical inhibition is normal in participants with FXS, while plasticity and metaplasticity appear abnormal. ASD participants showed abnormalities in plasticity and metaplasticity, as well as heterogeneity in intracortical inhibition. Our findings highlight the utility of noninvasive neurophysiological measures to translate insights from animal models to humans with neurodevelopmental disorders, and thus provide direct confirmation of cortical dysfunction in patients with FXS and ASD.

What saccadic eye movements tell us about TMS-induced neuromodulation of the DLPFC and mood changes: a pilot study in bipolar disorders.

Science.gov (United States)

Beynel, Lysianne; Chauvin, Alan; Guyader, Nathalie; Harquel, Sylvain; Szekely, David; Bougerol, Thierry; Marendaz, Christian

2014-01-01

The study assumed that the antisaccade (AS) task is a relevant psychophysical tool to assess (i) short-term neuromodulation of the dorsolateral prefrontal cortex (DLPFC) induced by intermittent theta burst stimulation (iTBS); and (ii) mood change occurring during the course of the treatment. Saccadic inhibition is known to strongly involve the DLPFC, whose neuromodulation with iTBS requires less stimulation time and lower stimulation intensity, as well as results in longer aftereffects than the conventional repetitive transcranial magnetic stimulation (rTMS). Active or sham iTBS was applied every day for 3 weeks over the left DLPFC of 12 drug-resistant bipolar depressed patients. To assess the iTBS-induced short-term neuromodulation, the saccadic task was performed just before (S1) and just after (S2) the iTBS session, the first day of each week. Mood was evaluated through Montgomery and Asberg Depression Rating Scale (MADRS) scores and the difference in scores between the beginning and the end of treatment was correlated with AS performance change between these two periods. As expected, only patients from the active group improved their performance from S1 to S2 and mood improvement was significantly correlated with AS performance improvement. In addition, the AS task also discriminated depressive bipolar patients from healthy control subjects. Therefore, the AS task could be a relevant and useful tool for clinicians to assess if the Transcranial magnetic stimulation (TMS)-induced short-term neuromodulation of the DLPFC occurs as well as a "trait vs. state" objective marker of depressive mood disorder.

12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels

Science.gov (United States)

DeCostanzo, Anthony J.; Voloshyna, Iryna; Rosen, Zev B.; Feinmark, Steven J.; Siegelbaum, Steven A.

2010-01-01

Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+ sources. Here we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta-burst stimulation (TBS) protocol, which depends on Ca2+ influx through both NMDA receptors and L-type voltage-gated Ca2+ channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+ influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+ influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE, a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP. PMID:20130191

Burst-suppression is reactive to photic stimulation in comatose children with acquired brain injury

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Nita, Dragos A.; Moldovan, Mihai; Sharma, Roy

2016-01-01

reactivity. We quantified reactivity by measuring the change in the burst ratio (fraction of time in burst) following photic stimulation. Results: Photic stimulation evoked bursts in all patients, resulting in a transient increase in the burst ratio, while the mean heart rate remained unchanged......Objective: Burst-suppression is an electroencephalographic pattern observed during coma. In individuals without known brain pathologies undergoing deep general anesthesia, somatosensory stimulation transiently increases the occurrence of bursts. We investigated the reactivity of burst......-suppression in children with acquired brain injury. Methods: Intensive care unit electroencephalographic monitoring recordings containing burst-suppression were obtained from 5 comatose children with acquired brain injury of various etiologies. Intermittent photic stimulation was performed at 1 Hz for 1 min to assess...

Network-targeted cerebellar transcranial magnetic stimulation improves attentional control

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Esterman, Michael; Thai, Michelle; Okabe, Hidefusa; DeGutis, Joseph; Saad, Elyana; Laganiere, Simon E.; Halko, Mark A.

2018-01-01

Developing non-invasive brain stimulation interventions to improve attentional control is extremely relevant to a variety of neurologic and psychiatric populations, yet few studies have identified reliable biomarkers that can be readily modified to improve attentional control. One potential biomarker of attention is functional connectivity in the core cortical network supporting attention - the dorsal attention network (DAN). We used a network-targeted cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance cortical functional connectivity in the DAN. Specifically, in healthy young adults we administered intermittent theta burst TMS (iTBS) to the midline cerebellar node of the DAN and, as a control, the right cerebellar node of the default mode network (DMN). These cerebellar targets were localized using individual resting-state fMRI scans. Participants completed assessments of both sustained (gradual onset continuous performance task, gradCPT) and transient attentional control (attentional blink) immediately before and after stimulation, in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation, participants had significantly fewer attentional lapses (lower commission error rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not affect gradCPT performance. Further, in the DAN condition, individuals with worse baseline gradCPT performance showed the greatest enhancement in gradCPT performance. These results suggest that temporarily increasing functional connectivity in the DAN via network-targeted cerebellar stimulation can enhance sustained attention, particularly in those with poor baseline performance. With regard to transient attention, TMS stimulation improved attentional blink performance across both stimulation sites, suggesting increasing functional connectivity in both networks can enhance this aspect of attention. These findings have important implications for intervention applications

Perturbation of the left inferior frontal gyrus triggers adaptive plasticity in the right homologous area during speech production

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Hartwigsen, Gesa; Saur, Dorothee; Price, Cathy J

2013-01-01

The role of the right hemisphere in aphasia recovery after left hemisphere damage remains unclear. Increased activation of the right hemisphere has been observed after left hemisphere damage. This may simply reflect a release from transcallosal inhibition that does not contribute to language...... functions. Alternatively, the right hemisphere may actively contribute to language functions by supporting disrupted processing in the left hemisphere via interhemispheric connections. To test this hypothesis, we applied off-line continuous theta burst stimulation (cTBS) over the left inferior frontal gyrus...... (IFG) in healthy volunteers, then used functional MRI to investigate acute changes in effective connectivity between the left and right hemispheres during repetition of auditory and visual words and pseudowords. In separate sessions, we applied cTBS over the left anterior IFG (aIFG) or posterior IFG (p...

What saccadic eye movements tell us about TMS-induced neuromodulation of the DLPFC and mood changes: a pilot study in bipolar disorders

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Lysianne eBeynel

2014-08-01

Full Text Available The study assumed that the antisaccade (AS task is a relevant psychophysical tool to assess (i short-term neuromodulation of the dorsolateral prefrontal cortex (DLPFC induced by intermittent theta burst stimulation (iTBS and (ii mood change occurring during the course of the treatment. Saccadic inhibition is known to strongly involve the DLPFC, whose neuromodulation with iTBS requires less stimulation time and lower stimulation intensity, as well as results in longer aftereffects than the conventional repetitive transcranial magnetic stimulation (rTMS. Active or sham iTBS was applied every day for three weeks over the left DLPFC of 12 drug-resistant bipolar depressed patients. To assess the iTBS-induced short-term neuromodulation, the saccadic task was performed just before (S1 and just after (S2 the iTBS session, the first day of each week. Mood was evaluated through MADRS scores and the difference in scores between the beginning and the end of treatment was correlated with AS performance change between these two periods. As expected, only patients from the active group improved their performance from S1 to S2 and mood improvement was significantly correlated with AS performance improvement. In addition, the AS task also discriminated depressive bipolar patients from healthy control subjects. Therefore, the AS task could be a relevant and useful tool for clinicians to assess if the TMS-induced short-term neuromodulation of the DLPFC occurs as well as a ‘trait vs. state’ objective marker of depressive mood disorder.

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

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Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter

2017-04-01

Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could

Improved Pain Relief With Burst Spinal Cord Stimulation for Two Weeks in Patients Using Tonic Stimulation: Results From a Small Clinical Study.

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Courtney, Peter; Espinet, Anthony; Mitchell, Bruce; Russo, Marc; Muir, Andrew; Verrills, Paul; Davis, Kristina

2015-07-01

Conventional spinal cord stimulation (SCS) delivers a tonic waveform with consistent stream of pulses; burst delivers groups of pulses separated by short pulse-free periods. The current study compared the short-term safety and efficacy of burst with tonic stimulation in subjects already receiving SCS. At 4 IRB-approved sites, 22 subjects previously implanted with an SCS device for intractable, chronic pain gave informed consent and received burst stimulation for 14 days. Subjects reported average daily Visual Analog Scale (VAS) for overall, trunk, and limb pain using tonic stimulation and after 7 and 14 days of burst stimulation. Thoughts about pain were assessed using the Pain Catastrophizing Scale. Areas of paresthesia were assessed during tonic and burst stimulation using body maps. Assessment of patient satisfaction and preferred stimulation occurred after 14 days of burst. Average daily overall VAS reduced 46% from a mean of 53.5 (±20.2) mm during tonic SCS to 28.5 (±18.1) mm during burst (p pain relief was the most common reason cited for preference. A majority of subjects reported improved pain relief using burst compared with tonic stimulation. Most subjects experienced less paresthesia during burst and preferred burst citing better pain relief. © 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

Temporal correlation between auditory neurons and the hippocampal theta rhythm induced by novel stimulations in awake guinea pigs.

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Liberman, Tamara; Velluti, Ricardo A; Pedemonte, Marisa

2009-11-17

The hippocampal theta rhythm is associated with the processing of sensory systems such as touch, smell, vision and hearing, as well as with motor activity, the modulation of autonomic processes such as cardiac rhythm, and learning and memory processes. The discovery of temporal correlation (phase locking) between the theta rhythm and both visual and auditory neuronal activity has led us to postulate the participation of such rhythm in the temporal processing of sensory information. In addition, changes in attention can modify both the theta rhythm and the auditory and visual sensory activity. The present report tested the hypothesis that the temporal correlation between auditory neuronal discharges in the inferior colliculus central nucleus (ICc) and the hippocampal theta rhythm could be enhanced by changes in sensory stimulation. We presented chronically implanted guinea pigs with auditory stimuli that varied over time, and recorded the auditory response during wakefulness. It was observed that the stimulation shifts were capable of producing the temporal phase correlations between the theta rhythm and the ICc unit firing, and they differed depending on the stimulus change performed. Such correlations disappeared approximately 6 s after the change presentation. Furthermore, the power of the hippocampal theta rhythm increased in half of the cases presented with a stimulation change. Based on these data, we propose that the degree of correlation between the unitary activity and the hippocampal theta rhythm varies with--and therefore may signal--stimulus novelty.

Excitability decreasing central motor plasticity is retained in multiple sclerosis patients

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Zeller Daniel

2012-09-01

Full Text Available Abstract Background Compensation of brain injury in multiple sclerosis (MS may in part work through mechanisms involving neuronal plasticity on local and interregional scales. Mechanisms limiting excessive neuronal activity may have special significance for retention and (re-acquisition of lost motor skills in brain injury. However, previous neurophysiological studies of plasticity in MS have investigated only excitability enhancing plasticity and results from neuroimaging are ambiguous. Thus, the aim of this study was to probe long-term depression-like central motor plasticity utilizing continuous theta-burst stimulation (cTBS, a non-invasive brain stimulation protocol. Because cTBS also may trigger behavioral effects through local interference with neuronal circuits, this approach also permitted investigating the functional role of the primary motor cortex (M1 in force control in patients with MS. Methods We used cTBS and force recordings to examine long-term depression-like central motor plasticity and behavioral consequences of a M1 lesion in 14 patients with stable mild-to-moderate MS (median EDSS 1.5, range 0 to 3.5 and 14 age-matched healthy controls. cTBS consisted of bursts (50 Hz of three subthreshold biphasic magnetic stimuli repeated at 5 Hz for 40 s over the hand area of the left M1. Corticospinal excitability was probed via motor-evoked potentials (MEP in the abductor pollicis brevis muscle over M1 before and after cTBS. Force production performance was assessed in an isometric right thumb abduction task by recording the number of hits into a predefined force window. Results cTBS reduced MEP amplitudes in the contralateral abductor pollicis brevis muscle to a comparable extent in control subjects (69 ± 22% of baseline amplitude, p  Conclusions Long-term depression-like plasticity remains largely intact in mild-to-moderate MS. Increasing brain injury may render the neuronal networks less responsive toward lesion

Area 5 influences excitability within the primary motor cortex in humans.

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Azra Premji

Full Text Available In non-human primates, Brodmann's area 5 (BA 5 has direct connectivity with primary motor cortex (M1, is largely dedicated to the representation of the hand and may have evolved with the ability to perform skilled hand movement. Less is known about human BA 5 and its interaction with M1 neural circuits related to hand control. The present study examines the influence of BA 5 on excitatory and inhibitory neural circuitry within M1 bilaterally before and after continuous (cTBS, intermittent (iTBS, and sham theta-burst stimulation (sham TBS over left hemisphere BA 5. Using single and paired-pulse TMS, measurements of motor evoked potentials (MEPs, short interval intracortical inhibition (SICI, and intracortical facilitation (ICF were quantified for the representation of the first dorsal interosseous muscle. Results indicate that cTBS over BA 5 influences M1 excitability such that MEP amplitudes are increased bilaterally for up to one hour. ITBS over BA 5 results in an increase in MEP amplitude contralateral to stimulation with a delayed onset that persists up to one hour. SICI and ICF were unaltered following TBS over BA 5. Similarly, F-wave amplitude and latency were unaltered following cTBS over BA 5. The data suggest that BA 5 alters M1 output directed to the hand by influencing corticospinal neurons and not interneurons that mediate SICI or ICF circuitry. Targeting BA 5 via cTBS and iTBS is a novel mechanism to powerfully modulate activity within M1 and may provide an avenue for investigating hand control in healthy populations and modifying impaired hand function in clinical populations.

Does rTMS Alter Neurocognitive Functioning in Patients with Panic Disorder/Agoraphobia? An fNIRS-Based Investigation of Prefrontal Activation during a Cognitive Task and Its Modulation via Sham-Controlled rTMS

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Saskia Deppermann

2014-01-01

Full Text Available Objectives. Neurobiologically, panic disorder (PD is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS, we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC could be replicated. As intermittent theta burst stimulation (iTBS modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Methods. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. Results. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG during the phonological task was found. Conclusion. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an “add-on” to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.

Does rTMS alter neurocognitive functioning in patients with panic disorder/agoraphobia? An fNIRS-based investigation of prefrontal activation during a cognitive task and its modulation via sham-controlled rTMS.

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Deppermann, Saskia; Vennewald, Nadja; Diemer, Julia; Sickinger, Stephanie; Haeussinger, Florian B; Notzon, Swantje; Laeger, Inga; Arolt, Volker; Ehlis, Ann-Christine; Zwanzger, Peter; Fallgatter, Andreas J

2014-01-01

Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an "add-on" to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.

Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults.

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Marielle eYoung-Bernier

2014-08-01

Full Text Available Cortical plasticity, including long-term potentiation (LTP-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI, a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS. Methods: SAI was first assessed by examining the modulation of motor evoked potentials (MEPs in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 HZ every 200 ms for 2 s with 8 s between trains, repeated 20 times. MEP responses (120% RMT were assessed immediately after iTBS and 5, 10, and 20 min post-application. Results: Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n=13 young and 10 older adults showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS. Conclusion: Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS.

Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults.

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Young-Bernier, Marielle; Tanguay, Annick N; Davidson, Patrick S R; Tremblay, François

2014-01-01

Cortical plasticity, including long-term potentiation (LTP)-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS) protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS) in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI), a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS. SAI was first assessed by examining the modulation of motor evoked potentials (MEPs) in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 Hz every 200 ms for 2 s with 8 s between trains, repeated 20 times). MEP responses (120% resting motor threshold (RMT)) were assessed immediately after iTBS and 5, 10, and 20 min post-application. Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n = 13 young and 10 older adults) showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS. Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS.

Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease.

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Suppa, A; Marsili, L; Belvisi, D; Conte, A; Iezzi, E; Modugno, N; Fabbrini, G; Berardelli, A

2011-02-01

In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors "Group" and "Time". After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (piTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features. Copyright © 2010 Elsevier Inc. All rights reserved.

Stimulation of auroral kilometric radiation by type III solar radio bursts

International Nuclear Information System (INIS)

Calvert, W.

1981-01-01

It has been found that the onset of auroral kilometric radiation (AKR) frequently coincides with the arrival of type III solar radio bursts. Although the AKR onsets are usually abrupt and appear to be spontaneous, they sometimes develop from a discrete frequency near the leading edge of a type III burst or sometimes occur at progressively lower frequencies following that edge. From this, and the absence of the related solar electrons in specific cases, it was concluded that the incoming type III waves were sometimes responsible for stimulating auroral kilometric radiation. It was estimated that intense, isolated type III bursts were capable of stimulating AKR roughly one third of the time, and that at least ten percent of the observed AKR onsets could be attributed to these and weaker bursts, including some barely detectable by the ISEE plasma wave receivers

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

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Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H

2016-03-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor

Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

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Mouna Maroun

2008-02-01

Full Text Available Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience.

Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

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Yarom, Orli; Maroun, Mouna; Richter-Levin, Gal

2008-01-01

Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP) of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI) and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS) reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience. PMID:18301720

A Preliminary Comparison of Motor Learning Across Different Non-invasive Brain Stimulation Paradigms Shows No Consistent Modulations

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Virginia Lopez-Alonso

2018-04-01

Full Text Available Non-invasive brain stimulation (NIBS has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1 on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI. We compared anodal transcranial direct current stimulation (tDCS, paired associative stimulation (PAS25, and intermittent theta burst stimulation (iTBS, along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants (n = 28 were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online, 1 day after training (consolidation, and 1 week after training (retention. We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning.

A Preliminary Comparison of Motor Learning Across Different Non-invasive Brain Stimulation Paradigms Shows No Consistent Modulations

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Lopez-Alonso, Virginia; Liew, Sook-Lei; Fernández del Olmo, Miguel; Cheeran, Binith; Sandrini, Marco; Abe, Mitsunari; Cohen, Leonardo G.

2018-01-01

Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1) on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task) and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI). We compared anodal transcranial direct current stimulation (tDCS), paired associative stimulation (PAS25), and intermittent theta burst stimulation (iTBS), along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants (n = 28) were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online), 1 day after training (consolidation), and 1 week after training (retention). We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning. PMID:29740271

Differences in motor evoked potentials induced in rats by transcranial magnetic stimulation under two separate anesthetics: implications for plasticity studies

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Matthew Sykes

2016-10-01

Full Text Available Repetitive transcranial magnetic stimulation (rTMS is primarily used in humans to change the state of corticospinal excitability. To assess the efficacy of different rTMS stimulation protocols, motor evoked potentials (MEPs are used as a readout due to their non-invasive nature. Stimulation of the motor cortex produces a response in a targeted muscle, and the amplitude of this twitch provides an indirect measure of the current state of the cortex. When applied to the motor cortex, rTMS can alter MEP amplitude, however results are variable between participants and across studies. In addition, the mechanisms underlying any change and its locus are poorly understood. In order to better understand these effects, MEPs have been investigated in vivo in animal models, primarily in rats. One major difference in protocols between rats and humans is the use of general anesthesia in animal experiments. Anesthetics are known to affect plasticity-like mechanisms and so may contaminate the effects of an rTMS protocol. In the present study, we explored the effect of anesthetic on MEP amplitude, recorded before and after intermittent theta burst stimulation (iTBS, a patterned rTMS protocol with reported facilitatory effects. MEPs were assessed in the brachioradialis muscle of the upper forelimb under two anesthetics: a xylazine/zoletil combination and urethane. We found MEPs could be induced under both anesthetics, with no differences in the resting motor threshold or the average baseline amplitudes. However, MEPs were highly variable between animals under both anesthetics, with the xylazine/zoletil combination showing higher variability and most prominently a rise in amplitude across the baseline recording period. Interestingly, application of iTBS did not facilitate MEP amplitude under either anesthetic condition. Although it is important to underpin human application of TMS with mechanistic examination of effects in animals, caution must be taken when

Differences in Motor Evoked Potentials Induced in Rats by Transcranial Magnetic Stimulation under Two Separate Anesthetics: Implications for Plasticity Studies.

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Sykes, Matthew; Matheson, Natalie A; Brownjohn, Philip W; Tang, Alexander D; Rodger, Jennifer; Shemmell, Jonathan B H; Reynolds, John N J

2016-01-01

Repetitive transcranial magnetic stimulation (rTMS) is primarily used in humans to change the state of corticospinal excitability. To assess the efficacy of different rTMS stimulation protocols, motor evoked potentials (MEPs) are used as a readout due to their non-invasive nature. Stimulation of the motor cortex produces a response in a targeted muscle, and the amplitude of this twitch provides an indirect measure of the current state of the cortex. When applied to the motor cortex, rTMS can alter MEP amplitude, however, results are variable between participants and across studies. In addition, the mechanisms underlying any change and its locus are poorly understood. In order to better understand these effects, MEPs have been investigated in vivo in animal models, primarily in rats. One major difference in protocols between rats and humans is the use of general anesthesia in animal experiments. Anesthetics are known to affect plasticity-like mechanisms and so may contaminate the effects of an rTMS protocol. In the present study, we explored the effect of anesthetic on MEP amplitude, recorded before and after intermittent theta burst stimulation (iTBS), a patterned rTMS protocol with reported facilitatory effects. MEPs were assessed in the brachioradialis muscle of the upper forelimb under two anesthetics: a xylazine/zoletil combination and urethane. We found MEPs could be induced under both anesthetics, with no differences in the resting motor threshold or the average baseline amplitudes. However, MEPs were highly variable between animals under both anesthetics, with the xylazine/zoletil combination showing higher variability and most prominently a rise in amplitude across the baseline recording period. Interestingly, application of iTBS did not facilitate MEP amplitude under either anesthetic condition. Although it is important to underpin human application of TMS with mechanistic examination of effects in animals, caution must be taken when selecting an

Continuous theta-burst stimulation of the primary motor cortex in essential tremor

DEFF Research Database (Denmark)

Hellriegel, Helge; Schulz, Eva M; Siebner, Hartwig R

2012-01-01

We investigated whether essential tremor (ET) can be altered by suppressing the corticospinal excitability in the primary motor cortex (M1) with transcranial magnetic stimulation.......We investigated whether essential tremor (ET) can be altered by suppressing the corticospinal excitability in the primary motor cortex (M1) with transcranial magnetic stimulation....

Primed Physical Therapy Enhances Recovery of Upper Limb Function in Chronic Stroke Patients.

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Ackerley, Suzanne J; Byblow, Winston D; Barber, P Alan; MacDonald, Hayley; McIntyre-Robinson, Andrew; Stinear, Cathy M

2016-05-01

Recovery of upper limb function is important for regaining independence after stroke. To test the effects of priming upper limb physical therapy with intermittent theta burst stimulation (iTBS), a form of noninvasive brain stimulation. Eighteen adults with first-ever chronic monohemispheric subcortical stroke participated in this randomized, controlled, triple-blinded trial. Intervention consisted of priming with real or sham iTBS to the ipsilesional primary motor cortex immediately before 45 minutes of upper limb physical therapy, daily for 10 days. Changes in upper limb function (Action Research Arm Test [ARAT]), upper limb impairment (Fugl-Meyer Scale), and corticomotor excitability, were assessed before, during, and immediately, 1 month and 3 months after the intervention. Functional magnetic resonance images were acquired before and at one month after the intervention. Improvements in ARAT were observed after the intervention period when therapy was primed with real iTBS, but not sham, and were maintained at 1 month. These improvements were not apparent halfway through the intervention, indicating a dose effect. Improvements in ARAT at 1 month were related to balancing of corticomotor excitability and an increase in ipsilesional premotor cortex activation during paretic hand grip. Two weeks of iTBS-primed therapy improves upper limb function at the chronic stage of stroke, for at least 1 month postintervention, whereas therapy alone may not be sufficient to alter function. This indicates a potential role for iTBS as an adjuvant to therapy delivered at the chronic stage. © The Author(s) 2015.

TMS evidence for a selective role of the precuneus in source memory retrieval.

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Bonnì, Sonia; Veniero, Domenica; Mastropasqua, Chiara; Ponzo, Viviana; Caltagirone, Carlo; Bozzali, Marco; Koch, Giacomo

2015-04-01

The posteromedial cortex including the precuneus (PC) is thought to be involved in episodic memory retrieval. Here we used continuous theta burst stimulation (cTBS) to disentangle the role of the precuneus in the recognition memory process in a sample of healthy subjects. During the encoding phase, subjects were presented with a series of colored pictures. Afterwards, during the retrieval phase, all previously presented items and a sample of new pictures were presented in black, and subjects were asked to indicate whether each item was new or old, and in the latter case to indicate the associated color. cTBS was delivered over PC, posterior parietal cortex (PPC) and vertex before the retrieval phase. The data were analyzed in terms of hits, false alarms, source errors and omissions. cTBS over the precuneus, but not over the PPC or the vertex, induced a selective decrease in source memory errors, indicating an improvement in context retrieval. All the other accuracy measurements were unchanged. These findings suggest a direct implication of the precuneus in successful context-dependent retrieval. Copyright © 2015 Elsevier B.V. All rights reserved.

Preliminary RAMI analysis of DFLL TBS for ITER

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Wang, Dagui [Key Laboratory of Neutronics and Radiation Safety, Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, Hefei, Anhui, 230031 (China); University of Science and Technology of China, Hefei, Anhui, 230031 (China); Yuan, Run [Key Laboratory of Neutronics and Radiation Safety, Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, Hefei, Anhui, 230031 (China); Wang, Jiaqun, E-mail: jiaqun.wang@fds.org.cn [Key Laboratory of Neutronics and Radiation Safety, Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, Hefei, Anhui, 230031 (China); Wang, Fang; Wang, Jin [Key Laboratory of Neutronics and Radiation Safety, Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, Hefei, Anhui, 230031 (China)

2016-11-15

Highlights: • We performed the functional analysis of the DFLL TBS. • We performed a failure mode analysis of the DFLL TBS. • We estimated the reliability and availability of the DFLL TBS. • The ITER RAMI approach was applied to the DFLL TBS for technical risk control in the design phase. - Abstract: ITER is the first fusion machine fully designed to prove the physics and technological basis for next fusion power plants. Among the main technical objectives of ITER is to test and validate design concepts of tritium breeding blankets relevant to the fusion power plants. To achieve this goal, China has proposed the dual functional lithium-lead test blanket module (DFLL TBM) concept design. The DFLL TBM and its associated ancillary system were called DFLL TBS. The DFLL TBS play a key role in next fusion reactor. In order to ensure reliable and available of DFLL TBS, the risk control project of DFLL TBS has been put on the schedule. As the stage of the ITER technical risk control policy, the RAMI (Reliability, Availability, Maintainability, Inspectability) approach was used to control the technical risk of ITER. In this paper, the RAMI approach was performed on the conceptual design of DFLL TBS. A functional breakdown was prepared on DFLL TBS, and the system was divided into 3 main functions and 72 basic functions. Based on the result of functional breakdown of DFLL TBS, the reliability block diagrams were prepared to estimate the reliability and availability of each function under the stipulated operating conditions. The inherent availability of the DFLL TBS expected after implementation of mitigation actions was calculated to be 98.57% over 2 years based on the ITER reliability database. A Failure Modes Effects and Criticality Analysis (FMECA) was performed with criticality charts highlighting the risk level of the different failure modes with regard to their probability of occurrence and their effects on the availability.

Inhibition of DNA Methylation Impairs Synaptic Plasticity during an Early Time Window in Rats

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Pablo Muñoz

2016-01-01

Full Text Available Although the importance of DNA methylation-dependent gene expression to neuronal plasticity is well established, the dynamics of methylation and demethylation during the induction and expression of synaptic plasticity have not been explored. Here, we combined electrophysiological, pharmacological, molecular, and immunohistochemical approaches to examine the contribution of DNA methylation and the phosphorylation of Methyl-CpG-binding protein 2 (MeCP2 to synaptic plasticity. We found that, at twenty minutes after theta burst stimulation (TBS, the DNA methylation inhibitor 5-aza-2-deoxycytidine (5AZA impaired hippocampal long-term potentiation (LTP. Surprisingly, after two hours of TBS, when LTP had become a transcription-dependent process, 5AZA treatment had no effect. By comparing these results to those in naive slices, we found that, at two hours after TBS, an intergenic region of the RLN gene was hypomethylated and that the phosphorylation of residue S80 of MeCP2 was decreased, while the phosphorylation of residue S421 was increased. As expected, 5AZA affected only the methylation of the RLN gene and exerted no effect on MeCP2 phosphorylation patterns. In summary, our data suggest that tetanic stimulation induces critical changes in synaptic plasticity that affects both DNA methylation and the phosphorylation of MeCP2. These data also suggest that early alterations in DNA methylation are sufficient to impair the full expression of LTP.

Inhibition of DNA Methylation Impairs Synaptic Plasticity during an Early Time Window in Rats.

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Muñoz, Pablo; Estay, Carolina; Díaz, Paula; Elgueta, Claudio; Ardiles, Álvaro O; Lizana, Pablo A

2016-01-01

Although the importance of DNA methylation-dependent gene expression to neuronal plasticity is well established, the dynamics of methylation and demethylation during the induction and expression of synaptic plasticity have not been explored. Here, we combined electrophysiological, pharmacological, molecular, and immunohistochemical approaches to examine the contribution of DNA methylation and the phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) to synaptic plasticity. We found that, at twenty minutes after theta burst stimulation (TBS), the DNA methylation inhibitor 5-aza-2-deoxycytidine (5AZA) impaired hippocampal long-term potentiation (LTP). Surprisingly, after two hours of TBS, when LTP had become a transcription-dependent process, 5AZA treatment had no effect. By comparing these results to those in naive slices, we found that, at two hours after TBS, an intergenic region of the RLN gene was hypomethylated and that the phosphorylation of residue S80 of MeCP2 was decreased, while the phosphorylation of residue S421 was increased. As expected, 5AZA affected only the methylation of the RLN gene and exerted no effect on MeCP2 phosphorylation patterns. In summary, our data suggest that tetanic stimulation induces critical changes in synaptic plasticity that affects both DNA methylation and the phosphorylation of MeCP2. These data also suggest that early alterations in DNA methylation are sufficient to impair the full expression of LTP.

Cortical and brainstem plasticity in Tourette syndrome and obsessive-compulsive disorder.

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Suppa, Antonio; Marsili, Luca; Di Stasio, Flavio; Berardelli, Isabella; Roselli, Valentina; Pasquini, Massimo; Cardona, Francesco; Berardelli, Alfredo

2014-10-01

Gilles de la Tourette syndrome is characterized by motor/vocal tics commonly associated with psychiatric disorders, including obsessive-compulsive disorder. We investigated primary motor cortex and brainstem plasticity in Tourette patients, exposed and unexposed to chronic drug treatment, with and without psychiatric disturbances. We also investigated primary motor cortex and brainstem plasticity in obsessive-compulsive disorder. We studied 20 Tourette patients with and without psychiatric disturbances, 15 with obsessive-compulsive disorder, and 20 healthy subjects. All groups included drug-naïve patients. We conditioned the left primary motor cortex with intermittent/continuous theta-burst stimulation and recorded motor evoked potentials. We conditioned the supraorbital nerve with facilitatory/inhibitory high-frequency stimulation and recorded the blink reflex late response area. In healthy subjects, intermittent theta-burst increased and continuous theta-burst stimulation decreased motor evoked potentials. Differently, intermittent theta-burst failed to increase and continuous theta-burst stimulation failed to decrease motor evoked potentials in Tourette patients, with and without psychiatric disturbances. In obsessive-compulsive disorder, intermittent/continuous theta-burst stimulation elicited normal responses. In healthy subjects and in subjects with obsessive-compulsive disorder, the blink reflex late response area increased after facilitatory high-frequency and decreased after inhibitory high-frequency stimulation. Conversely, in Tourette patients, with and without psychiatric disturbances, facilitatory/inhibitory high-frequency stimulation left the blink reflex late response area unchanged. Theta-burst and high-frequency stimulation elicited similar responses in drug-naïve and chronically treated patients. Tourette patients have reduced plasticity regardless of psychiatric disturbances. These findings suggest that abnormal plasticity contributes to the

Role of brain hemispheric dominance in anticipatory postural control strategies.

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Cioncoloni, David; Rosignoli, Deborah; Feurra, Matteo; Rossi, Simone; Bonifazi, Marco; Rossi, Alessandro; Mazzocchio, Riccardo

2016-07-01

Most of the cerebral functions are asymmetrically represented in the two hemispheres. Moreover, dexterity and coordination of the distal segment of the dominant limbs depend on cortico-motor lateralization. In this study, we investigated whether postural control may be also considered a lateralized hemispheric brain function. To this aim, 15 young subjects were tested in standing position by measuring center of pressure (COP) shifts along the anteroposterior axis (COP-Y) during dynamic posturography before and after continuous Theta Burst Stimulation (cTBS) intervention applied to the dominant or non-dominant M1 hand area as well as to the vertex. We show that when subjects were expecting a forward platform translation, the COP-Y was positioned significantly backward or forward after dominant or non-dominant M1 stimulation, respectively. We postulate that cTBS applied on M1 may have disrupted the functional connectivity between intra- and interhemispheric areas implicated in the anticipatory control of postural stability. This study suggests a functional asymmetry between the two homologous primary motor areas, with the dominant hemisphere playing a critical role in the selection of the appropriate postural control strategy.

Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

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Vincenzo eDi Lazzaro

2016-01-01

Full Text Available The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization.We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH and unaffected hemisphere (UH by measuring resting and active motor threshold and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI, to evidence hemispheric asymmetry. Active motor threshold differed significantly between AH and UH only in the male group (p=0.004, not in females (p>0.200, and both LIAMT and LIRMT were significantly higher in males than in females (respectively p=0.033 and p=0.042. LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery.

Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

Science.gov (United States)

Di Lazzaro, Vincenzo; Pellegrino, Giovanni; Di Pino, Giovanni; Ranieri, Federico; Lotti, Fiorenza; Florio, Lucia; Capone, Fioravante

2016-01-01

The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization. We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH) and unaffected hemisphere (UH) by measuring resting and active motor threshold (AMT) and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS) of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI), to evidence hemispheric asymmetry. AMT differed significantly between AH and UH only in the male group (p = 0.004), not in females (p > 0.200), and both LIAMT and LIRMT were significantly higher in males than in females (respectively p = 0.033 and p = 0.042). LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery. PMID:26858590

The Effect of Aerobic Exercise on Neuroplasticity within the Motor Cortex following Stroke.

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Kate Murdoch

Full Text Available Aerobic exercise is associated with enhanced plasticity in the motor cortex of healthy individuals, but the effect of aerobic exercise on neuroplasticity following a stroke is unknown.The aim of this study was to compare corticomotoneuronal excitability and neuroplasticity in the upper limb cortical representation following a single session of low intensity lower limb cycling, or a rest control condition.We recruited chronic stroke survivors to take part in three experimental conditions in a randomised, cross-over design. Corticomotoneuronal excitability was examined using transcranial magnetic stimulation to elicit motor evoked potentials in the affected first dorsal interosseus muscle. Following baseline measures, participants either cycled on a stationary bike at a low exercise intensity for 30 minutes, or remained resting in a seated position for 30 minutes. Neuroplasticity within the motor cortex was then examined using an intermittent theta burst stimulation (iTBS paradigm. During the third experimental condition, participants cycled for the 30 minutes but did not receive any iTBS.Twelve participants completed the study. We found no significant effect of aerobic exercise on corticomotoneuronal excitability when compared to the no exercise condition (P > 0.05 for all group and time comparisons. The use of iTBS did not induce a neuroplastic-like response in the motor cortex with or without the addition of aerobic exercise.Our results suggest that following a stroke, the brain may be less responsive to non-invasive brain stimulation paradigms that aim to induce short-term reorganisation, and aerobic exercise was unable to induce or improve this response.

The Effect of Aerobic Exercise on Neuroplasticity within the Motor Cortex following Stroke

Science.gov (United States)

Murdoch, Kate; Buckley, Jonathan D.; McDonnell, Michelle N.

2016-01-01

Background Aerobic exercise is associated with enhanced plasticity in the motor cortex of healthy individuals, but the effect of aerobic exercise on neuroplasticity following a stroke is unknown. Objective The aim of this study was to compare corticomotoneuronal excitability and neuroplasticity in the upper limb cortical representation following a single session of low intensity lower limb cycling, or a rest control condition. Methods We recruited chronic stroke survivors to take part in three experimental conditions in a randomised, cross-over design. Corticomotoneuronal excitability was examined using transcranial magnetic stimulation to elicit motor evoked potentials in the affected first dorsal interosseus muscle. Following baseline measures, participants either cycled on a stationary bike at a low exercise intensity for 30 minutes, or remained resting in a seated position for 30 minutes. Neuroplasticity within the motor cortex was then examined using an intermittent theta burst stimulation (iTBS) paradigm. During the third experimental condition, participants cycled for the 30 minutes but did not receive any iTBS. Results Twelve participants completed the study. We found no significant effect of aerobic exercise on corticomotoneuronal excitability when compared to the no exercise condition (P > 0.05 for all group and time comparisons). The use of iTBS did not induce a neuroplastic-like response in the motor cortex with or without the addition of aerobic exercise. Conclusions Our results suggest that following a stroke, the brain may be less responsive to non-invasive brain stimulation paradigms that aim to induce short-term reorganisation, and aerobic exercise was unable to induce or improve this response. PMID:27018862

Estrogen's Place in the Family of Synaptic Modulators.

Science.gov (United States)

Kramár, Enikö A; Chen, Lulu Y; Rex, Christopher S; Gall, Christine M; Lynch, Gary

2009-01-01

Estrogen, in addition to its genomic effects, triggers rapid synaptic changes in hippocampus and cortex. Here we summarize evidence that the acute actions of the steroid arise from actin signaling cascades centrally involved in long-term potentiation (LTP). A 10-min infusion of E2 reversibly increased fast EPSPs and promoted theta burst-induced LTP within adult hippocampal slices. The latter effect reflected a lowered threshold and an elevated ceiling for the potentiation effect. E2's actions on transmission and plasticity were completely blocked by latrunculin, a toxin that prevents actin polymerization. E2 also caused a reversible increase in spine concentrations of filamentous (F-) actin and markedly enhanced polymerization caused by theta burst stimulation (TBS). Estrogen activated the small GTPase RhoA, but not the related GTPase Rac, and phosphorylated (inactivated) synaptic cofilin, an actin severing protein targeted by RhoA. An inhibitor of RhoA kinase (ROCK) thoroughly suppressed the synaptic effects of E2. Collectively, these results indicate that E2 engages a RhoA >ROCK> cofilin> actin pathway also used by brain-derived neurotrophic factor and adenosine, and therefore belongs to a family of 'synaptic modulators' that regulate plasticity. Finally, we describe evidence that the acute signaling cascade is critical to the depression of LTP produced by ovariectomy.

Slow oscillation electrical brain stimulation during waking promotes EEG theta activity and memory encoding

DEFF Research Database (Denmark)

Kirov, Roumen; Weiss, Carsten; Siebner, Hartwig R

2009-01-01

typically occurring during this state of sleep were also enhanced. Here, we show that the same tSOS applied in the waking brain also induced an increase in endogenous EEG slow oscillations (0.4-1.2 Hz), although in a topographically restricted fashion. Applied during wakefulness tSOS, additionally, resulted......The application of transcranial slow oscillation stimulation (tSOS; 0.75 Hz) was previously shown to enhance widespread endogenous EEG slow oscillatory activity when applied during a sleep period characterized by emerging endogenous slow oscillatory activity. Processes of memory consolidation...... induced by tSOS critically depend on brain state. In response to tSOS during wakefulness the brain transposes stimulation by responding preferentially with theta oscillations and facilitated encoding....

Theta-rhythmic drive between medial septum and hippocampus in slow-wave sleep and microarousal: a Granger causality analysis.

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Kang, D; Ding, M; Topchiy, I; Shifflett, L; Kocsis, B

2015-11-01

Medial septum (MS) plays a critical role in controlling the electrical activity of the hippocampus (HIPP). In particular, theta-rhythmic burst firing of MS neurons is thought to drive lasting HIPP theta oscillations in rats during waking motor activity and REM sleep. Less is known about MS-HIPP interactions in nontheta states such as non-REM sleep, in which HIPP theta oscillations are absent but theta-rhythmic burst firing in subsets of MS neurons is preserved. The present study used Granger causality (GC) to examine the interaction patterns between MS and HIPP in slow-wave sleep (SWS, a nontheta state) and during its short interruptions called microarousals (a transient theta state). We found that during SWS, while GC revealed a unidirectional MS→HIPP influence over a wide frequency band (2-12 Hz, maximum: ∼8 Hz), there was no theta peak in the hippocampal power spectra, indicating a lack of theta activity in HIPP. In contrast, during microarousals, theta peaks were seen in both MS and HIPP power spectra and were accompanied by bidirectional GC with MS→HIPP and HIPP→MS theta drives being of equal magnitude. Thus GC in a nontheta state (SWS) vs. a theta state (microarousal) primarily differed in the level of HIPP→MS. The present findings suggest a modification of our understanding of the role of MS as the theta generator in two regards. First, a MS→HIPP theta drive does not necessarily induce theta field oscillations in the hippocampus, as found in SWS. Second, HIPP theta oscillations entail bidirectional theta-rhythmic interactions between MS and HIPP. Copyright © 2015 the American Physiological Society.

Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli

DEFF Research Database (Denmark)

Friis, P; Svehag, S E; Andersen, Ove

1991-01-01

. Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited...

Melodic Priming of Motor Sequence Performance: The Role of the Dorsal Premotor Cortex

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Marianne Anke Stephan

2016-05-01

Full Text Available The purpose of this study was to determine whether exposure to specific auditory sequences leads to the induction of new motor memories and to investigate the role of the dorsal premotor cortex (dPMC in this crossmodal learning process. Fifty-two young healthy non-musicians were familiarized with the sound to key-press mapping on a computer keyboard and tested on their baseline motor performance. Each participant received subsequently either continuous theta burst stimulation (cTBS or sham stimulation over the dPMC and was then asked to remember a 12-note melody without moving. For half of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (Congruent group. For the other half, the melody memorized was incongruent to the subsequent finger movement sequence (Incongruent group. Hearing a congruent melody led to significantly faster performance of a motor sequence immediately thereafter compared to hearing an incongruent melody. In addition, cTBS speeded up motor performance in both groups, possibly by relieving motor consolidation from interference by the declarative melody memorization task. Our findings substantiate recent evidence that exposure to a movement-related tone sequence can induce specific, crossmodal encoding of a movement sequence representation. They further suggest that cTBS over the dPMC may enhance early offline procedural motor skill consolidation in cognitive states where motor consolidation would normally be disturbed by concurrent declarative memory processes. These findings may contribute to a better understanding of auditory-motor system interactions and have implications for the development of new motor rehabilitation approaches using sound and non-invasive brain stimulation as neuromodulatory tools.

Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus.

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Vandecasteele, Marie; Varga, Viktor; Berényi, Antal; Papp, Edit; Barthó, Péter; Venance, Laurent; Freund, Tamás F; Buzsáki, György

2014-09-16

Theta oscillations in the limbic system depend on the integrity of the medial septum. The different populations of medial septal neurons (cholinergic and GABAergic) are assumed to affect different aspects of theta oscillations. Using optogenetic stimulation of cholinergic neurons in ChAT-Cre mice, we investigated their effects on hippocampal local field potentials in both anesthetized and behaving mice. Cholinergic stimulation completely blocked sharp wave ripples and strongly suppressed the power of both slow oscillations (0.5-2 Hz in anesthetized, 0.5-4 Hz in behaving animals) and supratheta (6-10 Hz in anesthetized, 10-25 Hz in behaving animals) bands. The same stimulation robustly increased both the power and coherence of theta oscillations (2-6 Hz) in urethane-anesthetized mice. In behaving mice, cholinergic stimulation was less effective in the theta (4-10 Hz) band yet it also increased the ratio of theta/slow oscillation and theta coherence. The effects on gamma oscillations largely mirrored those of theta. These findings show that medial septal cholinergic activation can both enhance theta rhythm and suppress peri-theta frequency bands, allowing theta oscillations to dominate.

Activation of the CREB/c-Fos Pathway during Long-Term Synaptic Plasticity in the Cerebellum Granular Layer

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Daniela Gandolfi

2017-06-01

Full Text Available The induction of long-term potentiation and depression (LTP and LTD is thought to trigger gene expression and protein synthesis, leading to consolidation of synaptic and neuronal changes. However, while LTP and LTD have been proposed to play important roles for sensori-motor learning in the cerebellum granular layer, their association with these mechanisms remained unclear. Here, we have investigated phosphorylation of the cAMP-responsive element binding protein (CREB and activation of the immediate early gene c-Fos pathway following the induction of synaptic plasticity by theta-burst stimulation (TBS in acute cerebellar slices. LTP and LTD were localized using voltage-sensitive dye imaging (VSDi. At two time points following TBS (15 min and 120 min, corresponding to the early and late phases of plasticity, slices were fixed and processed to evaluate CREB phosphorylation (P-CREB and c-FOS protein levels, as well as Creb and c-Fos mRNA expression. High levels of P-CREB and Creb/c-Fos were detected before those of c-FOS, as expected if CREB phosphorylation triggered gene expression followed by protein synthesis. No differences between control slices and slices stimulated with TBS were observed in the presence of an N-methyl-D-aspartate receptor (NMDAR antagonist. Interestingly, activation of the CREB/c-Fos system showed a relevant degree of colocalization with long-term synaptic plasticity. These results show that NMDAR-dependent plasticity at the cerebellum input stage bears about transcriptional and post-transcriptional processes potentially contributing to cerebellar learning and memory consolidation.

Increased Reliance on Value-based Decision Processes Following Motor Cortex Disruption.

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Zénon, Alexandre; Klein, Pierre-Alexandre; Alamia, Andrea; Boursoit, François; Wilhelm, Emmanuelle; Duque, Julie

2015-01-01

During motor decision making, the neural activity in primary motor cortex (M1) encodes dynamically the competition occurring between potential action plans. A common view is that M1 represents the unfolding of the outcome of a decision process taking place upstream. Yet, M1 could also be directly involved in the decision process. Here we tested this hypothesis by assessing the effect of M1 disruption on a motor decision-making task. We applied continuous theta burst stimulation (cTBS) to inhibit either left or right M1 in different groups of subjects and included a third control group with no stimulation. Following cTBS, participants performed a task that required them to choose between two finger key-presses with the right hand according to both perceptual and value-based information. Effects were assessed by means of generalized linear mixed models and computational simulations. In all three groups, subjects relied both on perceptual (P < 0.0001) and value-based information (P = 0.003) to reach a decision. Yet, left M1 disruption led to an increased reliance on value-based information (P = 0.03). This result was confirmed by a computational model showing an increased weight of the valued-based process on the right hand finger choices following left M1 cTBS (P < 0.01). These results indicate that M1 is involved in motor decision making, possibly by weighting the final integration of multiple sources of evidence driving motor behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Current status of accident analysis for Korean HCCR TBS

Energy Technology Data Exchange (ETDEWEB)

Ahn, Mu-Young, E-mail: myahn74@nfri.re.kr [National Fusion Research Institute, Daejeon (Korea, Republic of); Jin, Hyung Gon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cho, Seungyon [National Fusion Research Institute, Daejeon (Korea, Republic of); Lee, Dong Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Ku, Duck Young; Park, Yi-Hyun; Kim, Chang-Shuk; Lee, Youngmin [National Fusion Research Institute, Daejeon (Korea, Republic of)

2014-10-15

Korea has decided to test Helium Cooled Ceramic Reflector (HCCR) Test Blanket Module (TBM) in ITER and design of the TBM with its ancillary systems, i.e. Test Blanket System (TBS), is under progress. Since the TBM is operated at elevated temperature with high heat load, safety consideration is essential in design procedure. In this paper, preliminary accident analysis results for the current HCCR TBS design on selected scenarios are presented as an important part of safety assessments. To simulate transient thermo-hydraulic behavior, GAMMA-FR code which has been developed in Korea for fusion applications was used. The main cooling and tritium extraction circuit systems, as well as the TBM, were simulated and the main components in the TBS were modeled as the associated heat structures. The important accident scenarios were produced and summarized in the paper considering the HCCR TBS design and ITER conditions, which cover in-vessel Loss Of Coolant Accident (LOCA), in-box LOCA, ex-vessel LOCA, Loss Of Flow Accident (LOFA), Loss Of Heat Sink Accident (LOHSA) and purge pipe rupture case. The accident analysis based on the selected scenarios was performed and it was found that the current design of the HCCR TBS meets the thermo-hydraulic safety requirements.

Current status of accident analysis for Korean HCCR TBS

International Nuclear Information System (INIS)

Ahn, Mu-Young; Jin, Hyung Gon; Cho, Seungyon; Lee, Dong Won; Ku, Duck Young; Park, Yi-Hyun; Kim, Chang-Shuk; Lee, Youngmin

2014-01-01

Korea has decided to test Helium Cooled Ceramic Reflector (HCCR) Test Blanket Module (TBM) in ITER and design of the TBM with its ancillary systems, i.e. Test Blanket System (TBS), is under progress. Since the TBM is operated at elevated temperature with high heat load, safety consideration is essential in design procedure. In this paper, preliminary accident analysis results for the current HCCR TBS design on selected scenarios are presented as an important part of safety assessments. To simulate transient thermo-hydraulic behavior, GAMMA-FR code which has been developed in Korea for fusion applications was used. The main cooling and tritium extraction circuit systems, as well as the TBM, were simulated and the main components in the TBS were modeled as the associated heat structures. The important accident scenarios were produced and summarized in the paper considering the HCCR TBS design and ITER conditions, which cover in-vessel Loss Of Coolant Accident (LOCA), in-box LOCA, ex-vessel LOCA, Loss Of Flow Accident (LOFA), Loss Of Heat Sink Accident (LOHSA) and purge pipe rupture case. The accident analysis based on the selected scenarios was performed and it was found that the current design of the HCCR TBS meets the thermo-hydraulic safety requirements

Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli

DEFF Research Database (Denmark)

Friis, P; Svehag, S E; Andersen, Ove

1991-01-01

. Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited......Conglutinin is a mammalian C-type lectin which shows anti-bacterial activity when tested in vivo and in vitro. This study concerns the effect of conglutinin on the respiratory burst of murine spleen cells, using a chemiluminescence assay for measurement of generated reactive oxygen metabolites...

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.

Science.gov (United States)

Zareen, N; Shinozaki, M; Ryan, D; Alexander, H; Amer, A; Truong, D Q; Khadka, N; Sarkar, A; Naeem, S; Bikson, M; Martin, J H

2017-11-01

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury+stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Theta vectors and quantum theta functions

International Nuclear Information System (INIS)

Chang-Young, Ee; Kim, Hoil

2005-01-01

In this paper, we clarify the relation between Manin's quantum theta function and Schwarz's theta vector. We do this in comparison with the relation between the kq representation, which is equivalent to the classical theta function, and the corresponding coordinate space wavefunction. We first explain the equivalence relation between the classical theta function and the kq representation in which the translation operators of the phase space are commuting. When the translation operators of the phase space are not commuting, then the kq representation is no longer meaningful. We explain why Manin's quantum theta function, obtained via algebra (quantum torus) valued inner product of the theta vector, is a natural choice for the quantum version of the classical theta function. We then show that this approach holds for a more general theta vector containing an extra linear term in the exponent obtained from a holomorphic connection of constant curvature than the simple Gaussian one used in Manin's construction

Learning stage-dependent effect of M1 disruption on value-based motor decisions.

Science.gov (United States)

Derosiere, Gerard; Vassiliadis, Pierre; Demaret, Sophie; Zénon, Alexandre; Duque, Julie

2017-11-15

The present study aimed at characterizing the impact of M1 disruption on the implementation of implicit value information in motor decisions, at both early stages (during reinforcement learning) and late stages (after consolidation) of action value encoding. Fifty subjects performed, over three consecutive days, a task that required them to select between two finger responses according to the color (instruction) and to the shape (implicit, undisclosed rule) of an imperative signal: considering the implicit rule in addition to the instruction allowed subjects to earn more money. We investigated the functional contribution of M1 to the implementation of the implicit rule in subjects' motor decisions. Continuous theta burst stimulation (cTBS) was applied over M1 either on Day 1 or on Day 3, producing a temporary lesion either during reinforcement learning (cTBS Learning group) or after consolidation of the implicit rule, during decision-making (cTBS Decision group), respectively. Interestingly, disrupting M1 activity on Day 1 improved the reliance on the implicit rule, plausibly because M1 cTBS increased dopamine release in the putamen in an indirect way. This finding corroborates the view that cTBS may affect activity in unstimulated areas, such as the basal ganglia. Notably, this effect was short-lasting; it did not persist overnight, suggesting that the functional integrity of M1 during learning is a prerequisite for the consolidation of implicit value information to occur. Besides, cTBS over M1 did not impact the use of the implicit rule when applied on Day 3, although it did so when applied on Day 2 in a recent study where the reliance on the implicit rule declined following cTBS (Derosiere et al., 2017). Overall, these findings indicate that the human M1 is functionally involved in the consolidation and implementation of implicit value information underlying motor decisions. However, M1 contribution seems to vanish as subjects become more experienced in using

The Effects of Theta and Gamma tACS on Working Memory and Electrophysiology

Directory of Open Access Journals (Sweden)

Anja Pahor

2018-01-01

Full Text Available A single blind sham-controlled study was conducted to explore the effects of theta and gamma transcranial alternating current stimulation (tACS on offline performance on working memory tasks. In order to systematically investigate how specific parameters of tACS affect working memory, we manipulated the frequency of stimulation (theta frequency vs. gamma frequency, the type of task (n-back vs. change detection task and the content of the tasks (verbal vs. figural stimuli. A repeated measures design was used that consisted of three sessions: theta tACS, gamma tACS and sham tACS. In total, four experiments were conducted which differed only with respect to placement of tACS electrodes (bilateral frontal, bilateral parietal, left fronto-parietal and right-fronto parietal. Healthy female students (N = 72 were randomly assigned to one of these groups, hence we were able to assess the efficacy of theta and gamma tACS applied over different brain areas, contrasted against sham stimulation. The pre-post/sham resting electroencephalogram (EEG analysis showed that theta tACS significantly affected theta amplitude, whereas gamma tACS had no significant effect on EEG amplitude in any of the frequency bands of interest. Gamma tACS did not significantly affect working memory performance compared to sham, and theta tACS led to inconsistent changes in performance on the n-back tasks. Active theta tACS significantly affected P3 amplitude and latency during performance on the n-back tasks in the bilateral parietal and right-fronto parietal protocols.

A 2-center Comparative Study on Tonic Versus Burst Spinal Cord Stimulation: Amount of Responders and Amount of Pain Suppression

NARCIS (Netherlands)

Ridder, D.M.D.; Lenders, M.W.P.M.; de Vos, Cecilia Cecilia Clementine; Dijkstra-Scholten, C.R.N.; Wolters, R.R.N.; Vancamp, T.P.T.; Van Looy, P.R.N.; Van Havenbergh, T.M.D.; Vanneste, S.

2015-01-01

Introduction: Spinal cord stimulation is a safe and effective procedure applied for medically intractable neuropathic pain and failed back surgery syndrome. Recently, a novel stimulation paradigm was developed, called burst stimulation consisting of intermittent packets of closely spaced

Inzicht in de verblijfsduur van tbs-gestelden : Cijfers en mogelijke verklaringen

NARCIS (Netherlands)

Nagtegaal, M.H.; Horst, R.P. van der; Schönberger, H.J.M.

2011-01-01

De belangrijkste doelstellingen van het onderzoek waren:Inzicht bieden in de ontwikkeling van de verblijfsduur van tbs-gestelden in de periode 1990-2009.Inzicht bieden in mogelijke verklaringen voor de ontwikkeling van de verblijfsduur van tbs-gestelden in de periode 1990-2009.

The lumbar spine age-related degenerative disease influences the BMD not the TBS: the Osteolaus cohort.

Science.gov (United States)

Padlina, I; Gonzalez-Rodriguez, E; Hans, D; Metzger, M; Stoll, D; Aubry-Rozier, B; Lamy, O

2017-03-01

We evaluated the influence of degenerative disease and fractured vertebra on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) in 1500 women aged 50-80 years. TBS was not affected by a degenerative disease. While BMD increases after 62.5 years, TBS continues to decline. TBS should play a leading role in lumbar spine evaluation. After menopause, lumbar spine (LS) BMD and TBS values decrease. Degenerative disease (DD) increases with age and affect LS BMD. The aim of this study was to measure changes in LS BMD and TBS in women 50 to 80 years old, taking into account the impact of fractured vertebrae and DD. LS BMD, TBS, and vertebral fracture assessment were evaluated in the OsteoLaus cohort (1500 women, 50-80 years old). The exams were analyzed following ISCD guidelines to identify vertebrae with fractures or DD (Vex). 1443 women were enrolled: mean age 66.7 ± 11.7 years, BMI 25.7 ± 4.4. LS BMD and TBS were weakly correlated (r2 = 0.16). The correlation (Vex excluded) between age and BMD was +0.03, between age and TBS -0.34. According to age group, LS BMD was 1.2 to 3.2% higher before excluding Vex (p < 0.001). TBS had an insignificant change of <1% after excluding Vex. LS BMD (Vex) decreased by 4.6% between 52.5 and 62.5 years, and increased by 2.6% between 62.5 and 77.5 years. TBS (Vex excluded) values decreased steadily with age with an overall loss of 8.99% between 52.5 and 77.5 years. Spine TBS, femoral neck, and total hip BMD gradually decreased with age, reaching one SD between the oldest and youngest group. TBS is not affected by DD. While BMD increases after 62.5 years, TBS continues to decline. For lumbar spine evaluation, in view of its independence from DD, TBS should play a leading role in the diagnosis in complement to BMD.

Trapped-Particle Instability Leading to Bursting in Stimulated Raman Scattering Simulations

International Nuclear Information System (INIS)

Brunner, S.; Valeo, E.

2001-01-01

Nonlinear, kinetic simulations of Stimulated Raman Scattering (SRS) for laser-fusion-relevant conditions present a bursting behavior. Different explanations for this regime has been given in previous studies: Saturation of SRS by increased nonlinear Landau damping [K. Estabrook et al., Phys. Fluids B 1 (1989) 1282] and detuning due to the nonlinear frequency shift of the plasma wave [H.X. Vu et al., Phys. Rev. Lett. 86 (2001) 4306]. Another mechanism, also assigning a key role to the trapped electrons, is proposed here: The break-up of the plasma wave through the trapped-particle instability

Role of Oculoproprioception in Coding the Locus of Attention.

Science.gov (United States)

Odoj, Bartholomaeus; Balslev, Daniela

2016-03-01

The most common neural representations for spatial attention encode locations retinotopically, relative to center of gaze. To keep track of visual objects across saccades or to orient toward sounds, retinotopic representations must be combined with information about the rotation of one's own eyes in the orbits. Although gaze input is critical for a correct allocation of attention, the source of this input has so far remained unidentified. Two main signals are available: corollary discharge (copy of oculomotor command) and oculoproprioception (feedback from extraocular muscles). Here we asked whether the oculoproprioceptive signal relayed from the somatosensory cortex contributes to coding the locus of attention. We used continuous theta burst stimulation (cTBS) over a human oculoproprioceptive area in the postcentral gyrus (S1EYE). S1EYE-cTBS reduces proprioceptive processing, causing ∼1° underestimation of gaze angle. Participants discriminated visual targets whose location was cued in a nonvisual modality. Throughout the visual space, S1EYE-cTBS shifted the locus of attention away from the cue by ∼1°, in the same direction and by the same magnitude as the oculoproprioceptive bias. This systematic shift cannot be attributed to visual mislocalization. Accuracy of open-loop pointing to the same visual targets, a function thought to rely mainly on the corollary discharge, was unchanged. We argue that oculoproprioception is selective for attention maps. By identifying a potential substrate for the coupling between eye and attention, this study contributes to the theoretical models for spatial attention.

Theta oscillations locked to intended actions rhythmically modulate perception.

Science.gov (United States)

Tomassini, Alice; Ambrogioni, Luca; Medendorp, W Pieter; Maris, Eric

2017-07-07

Ongoing brain oscillations are known to influence perception, and to be reset by exogenous stimulations. Voluntary action is also accompanied by prominent rhythmic activity, and recent behavioral evidence suggests that this might be coupled with perception. Here, we reveal the neurophysiological underpinnings of this sensorimotor coupling in humans. We link the trial-by-trial dynamics of EEG oscillatory activity during movement preparation to the corresponding dynamics in perception, for two unrelated visual and motor tasks. The phase of theta oscillations (~4 Hz) predicts perceptual performance, even >1 s before movement. Moreover, theta oscillations are phase-locked to the onset of the movement. Remarkably, the alignment of theta phase and its perceptual relevance unfold with similar non-monotonic profiles, suggesting their relatedness. The present work shows that perception and movement initiation are automatically synchronized since the early stages of motor planning through neuronal oscillatory activity in the theta range.

CA1 Pyramidal Cell Theta-Burst Firing Triggers Endocannabinoid-Mediated Long-Term Depression at Both Somatic and Dendritic Inhibitory Synapses

Science.gov (United States)

Younts, Thomas J.; Chevaleyre, Vivien

2013-01-01

Endocannabinoids (eCBs) are retrograde lipid messengers that, by targeting presynaptic type 1 cannabinoid receptors (CB1Rs), mediate short- and long-term synaptic depression of neurotransmitter release throughout the brain. Short-term depression is typically triggered by postsynaptic, depolarization-induced calcium rises, whereas long-term depression is induced by synaptic activation of Gq/11 protein-coupled receptors. Here we report that a physiologically relevant pattern of postsynaptic activity, in the form of theta-burst firing (TBF) of hippocampal CA1 pyramidal neurons, can trigger long-term depression of inhibitory transmission (iLTD) in rat hippocampal slices. Paired recordings between CA1 interneurons and pyramidal cells, followed by post hoc morphological reconstructions of the interneurons' axon, revealed that somatic and dendritic inhibitory synaptic inputs equally expressed TBF-induced iLTD. Simultaneous recordings from neighboring pyramidal cells demonstrated that eCB signaling triggered by TBF was highly restricted to only a single, active cell. Furthermore, pairing submaximal endogenous activation of metabotropic glutamate or muscarinic acetylcholine receptors with submaximal TBF unmasked associative iLTD. Although CB1Rs are also expressed at Schaffer-collateral excitatory terminals, long-term plasticity under various recording conditions was spared at these synapses. Consistent with this observation, TBF also shifted the balance of excitation and inhibition in favor of excitatory throughput, thereby altering information flow through the CA1 circuit. Given the near ubiquity of burst-firing activity patterns and CB1R expression in the brain, the properties described here may be a general means by which neurons fine tune the strength of their inputs in a cell-wide and cell-specific manner. PMID:23966696

409-Tb/s + 409-Tb/s crosstalk suppressed bidirectional MCF transmission over 450 km using propagation-direction interleaving

DEFF Research Database (Denmark)

Sano, Akihide; Takara, Hidehiko; Kobayashi, Takayuki

2013-01-01

We demonstrate bidirectional transmission over 450 km of newly-developed dual-ring structured 12-core fiber with large effective area and low crosstalk. Inter-core crosstalk is suppressed by employing propagation-direction interleaving, and 409-Tb/s capacities are achieved for both directions...

Long-term plasticity in identified hippocampal GABAergic interneurons in the CA1 area in vivo.

Science.gov (United States)

Lau, Petrina Yau-Pok; Katona, Linda; Saghy, Peter; Newton, Kathryn; Somogyi, Peter; Lamsa, Karri P

2017-05-01

Long-term plasticity is well documented in synapses between glutamatergic principal cells in the cortex both in vitro and in vivo. Long-term potentiation (LTP) and -depression (LTD) have also been reported in glutamatergic connections to hippocampal GABAergic interneurons expressing parvalbumin (PV+) or nitric oxide synthase (NOS+) in brain slices, but plasticity in these cells has not been tested in vivo. We investigated synaptically-evoked suprathreshold excitation of identified hippocampal neurons in the CA1 area of urethane-anaesthetized rats. Neurons were recorded extracellularly with glass microelectrodes, and labelled with neurobiotin for anatomical analyses. Single-shock electrical stimulation of afferents from the contralateral CA1 elicited postsynaptic action potentials with monosynaptic features showing short delay (9.95 ± 0.41 ms) and small jitter in 13 neurons through the commissural pathway. Theta-burst stimulation (TBS) generated LTP of the synaptically-evoked spike probability in pyramidal cells, and in a bistratified cell and two unidentified fast-spiking interneurons. On the contrary, PV+ basket cells and NOS+ ivy cells exhibited either LTD or LTP. An identified axo-axonic cell failed to show long-term change in its response to stimulation. Discharge of the cells did not explain whether LTP or LTD was generated. For the fast-spiking interneurons, as a group, no correlation was found between plasticity and local field potential oscillations (1-3 or 3-6 Hz components) recorded immediately prior to TBS. The results demonstrate activity-induced long-term plasticity in synaptic excitation of hippocampal PV+ and NOS+ interneurons in vivo. Physiological and pathological activity patterns in vivo may generate similar plasticity in these interneurons.

Pipe stress analysis on HCCR-TBS ancillary systems in conceptual design

International Nuclear Information System (INIS)

Ahn, Mu-Young; Cho, Seungyon; Lee, Eo Hwak; Park, Yi-Hyun; Lee, Youngmin

2016-01-01

Highlights: • Pipe stress is performed on Korean HCCR-TBS for the load combinations including seismic events. • The resultant stress meets the requirement of the design code & standard except one position where modification is needed. • The results gives useful information for the design evolution in the next desgin phase. - Abstract: Korean Helium Cooled Ceramic Reflector (HCCR) Test Blanket System (TBS) will be tested in ITER to demonstrate feasibility of the breeding blanket concept. The HCCR-TBS comprises Test Blanket Module (TBM) with associated shield, and ancillary systems located in various positions of ITER building. Currently, conceptual design for the HCCR-TBS is in progress. This paper presents pipe stress analysis results for the HCCR-TBS ancillary systems. The pipe stress analysis was performed in accordance with ASME B31.3 for major pipes of the Helium Cooling System (HCS) and the Coolant Purification System (CPS), which are operated in high pressure and temperature. The pipe stress for various load cases and load combinations were calculated. Operational pressure and temperature during plasma operation are applied as pressure load and thermal load, respectively. In addition seismic events were combined to investigate the code compliance for sustained load case and occasional load case. It was confirmed that the resultant stress meets the requirements of ASME B31.3 except one position in which it needs modification. These results give useful information for the next design phase, for example, nozzle loads for the component selection, the support design parameters, etc.

Pipe stress analysis on HCCR-TBS ancillary systems in conceptual design

Energy Technology Data Exchange (ETDEWEB)

Ahn, Mu-Young, E-mail: myahn74@nfri.re.kr [National Fusion Research Institute, Daejeon (Korea, Republic of); Cho, Seungyon [National Fusion Research Institute, Daejeon (Korea, Republic of); Lee, Eo Hwak [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Park, Yi-Hyun; Lee, Youngmin [National Fusion Research Institute, Daejeon (Korea, Republic of)

2016-11-01

Highlights: • Pipe stress is performed on Korean HCCR-TBS for the load combinations including seismic events. • The resultant stress meets the requirement of the design code & standard except one position where modification is needed. • The results gives useful information for the design evolution in the next desgin phase. - Abstract: Korean Helium Cooled Ceramic Reflector (HCCR) Test Blanket System (TBS) will be tested in ITER to demonstrate feasibility of the breeding blanket concept. The HCCR-TBS comprises Test Blanket Module (TBM) with associated shield, and ancillary systems located in various positions of ITER building. Currently, conceptual design for the HCCR-TBS is in progress. This paper presents pipe stress analysis results for the HCCR-TBS ancillary systems. The pipe stress analysis was performed in accordance with ASME B31.3 for major pipes of the Helium Cooling System (HCS) and the Coolant Purification System (CPS), which are operated in high pressure and temperature. The pipe stress for various load cases and load combinations were calculated. Operational pressure and temperature during plasma operation are applied as pressure load and thermal load, respectively. In addition seismic events were combined to investigate the code compliance for sustained load case and occasional load case. It was confirmed that the resultant stress meets the requirements of ASME B31.3 except one position in which it needs modification. These results give useful information for the next design phase, for example, nozzle loads for the component selection, the support design parameters, etc.

A configurable FPGA FEC unit for Tb/s optical communication

DEFF Research Database (Denmark)

Andersen, Jakob Dahl; Larsen, Knud J.; Bering Bøgh, Christian

2017-01-01

Decoding of FEC (forward error correction) for optical communication beyond 1 Tb/s is investigated. A configurable single FPGA solution is presented having configurations supporting bit-rates in the range from 40 Gb/s to 1.6 Tb/s. The design allows for trade-offs of bit-rate, footprint, and latency...... within the resources of the FPGA. A proof-of-concept lab experiment at 40 Gb/s was conducted and pre-FEC — post-FEC performance validated with simulated results....

Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat.

Science.gov (United States)

Villette, Vincent; Poindessous-Jazat, Frédérique; Simon, Axelle; Léna, Clément; Roullot, Elodie; Bellessort, Brice; Epelbaum, Jacques; Dutar, Patrick; Stéphan, Aline

2010-08-18

The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (symbol) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid beta (Abeta) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Abeta injections progressively impaired behavioral performances, the associated hippocampal theta power, and theta frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the theta rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Abeta treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.

Theta-frequency resonance at the cerebellum input stage improves spike-timing on the millisecond time-scale

Directory of Open Access Journals (Sweden)

Daniela eGandolfi

2013-04-01

Full Text Available The neuronal circuits of the brain are thought to use resonance and oscillations to improve communication over specific frequency bands (Llinas, 1988; Buzsaki, 2006. However, the properties and mechanism of these phenomena in brain circuits remain largely unknown. Here we show that, at the cerebellum input stage, the granular layer generates its maximum response at 5-7 Hz both in vivo following tactile sensory stimulation of the whisker pad and in acute slices following mossy fiber-bundle stimulation. The spatial analysis of granular layer activity performed using voltage-sensitive dye (VSD imaging revealed 5-7 Hz resonance covering large granular layer areas. In single granule cells, resonance appeared as a reorganization of output spike bursts on the millisecond time-scale, such that the first spike occurred earlier and with higher temporal precision and the probability of spike generation increased. Resonance was independent from circuit inhibition, as it persisted with little variation in the presence of the GABAA receptor blocker, gabazine. However, circuit inhibition reduced the resonance area more markedly at 7 Hz. Simulations with detailed computational models suggested that resonance depended on intrinsic granule cells ionic mechanisms: specifically, Kslow (M-like and KA currents acted as resonators and the persistent Na current and NMDA current acted as amplifiers. This form of resonance may play an important role for enhancing coherent spike emission from the granular layer when theta-frequency bursts are transmitted by the cerebral cortex and peripheral sensory structures during sensory-motor processing, cognition and learning.

The central responsiveness of the acute cerveau isolé rat.

Science.gov (United States)

User, P; Gottesmann, C

1982-01-01

The electrophysiological patterns of the frontal cortex and dorsal hippocampus were studied in the acute cerveau isolé rat. Central and peripheral stimulations were performed in order to modulate these patterns. The results showed that the permanent alternation of high amplitude spindle bursts and low voltage activity in the anterior neocortex of the acute cerveau isolé was influenced neither by olfactory nor by posterior hypothalamic stimulation. In contrast, these two kinds of stimulation easily modulated the continuous low frequency theta rhythm, recorded in the dorsal hippocampus, in terms of amplitude and in overall frequency. This modulation of the theta rhythm in the acute cerveau isolé rat mimics the changes observed when the normal rat comes from the intermediate stage of sleep (as characterized in the the acute intercollicular transected rat by high amplitude spindle bursts at frontal cortex level and low frequency theta activity in the dorsal hippocampus) to rapid sleep. These results further suggest that, during the intermediate stage (as in the cerveau isolé preparation), the hippocampus montonous theta activity appears through a brainstem disinhibitory process releasing the forebrain limbic pacemaker(s). During the following rapid sleep phase, the theta rhythm would be modulated by pontine activity influences acting on the theta generators.

gTBS: A green Task-Based Sensing for energy efficient Wireless Sensor Networks

KAUST Repository

Al-Halafi, Abdullah

2016-09-08

Wireless sensor networks (WSN) are widely used to sense and measure physical conditions for different purposes and within different regions. However due to the limited lifetime of the sensor\\'s energy source, many efforts are made to design energy efficient WSN. As a result, many techniques were presented in the literature such as power adaptation, sleep and wake-up, and scheduling in order to enhance WSN lifetime. These techniques where presented separately and shown to achieve some gain in terms of energy efficiency. In this paper, we present an energy efficient cross layer design for WSN that we named \\'green Task-Based Sensing\\' (gTBS) scheme. The gTBS design is a task based sensing scheme that not only prevents wasting power in unnecessary signaling, but also utilizes several techniques for achieving reliable and energy efficient WSN. The proposed gTBS combines the power adaptation with a sleep and wake-up technique that allows inactive nodes to sleep. Also, it adopts a gradient-oriented unicast approach to overcome the synchronization problem, minimize network traffic hurdles, and significantly reduce the overall power consumption of the network. We implement the gTBS on a testbed and we show that it reduces the power consumption by a factor of 20%-55% compared to traditional TBS. It also reduces the delay by 54%-145% and improves the delivery ratio by 24%-73%. © 2016 IEEE.

Comparison of Anti-Inflammatory Effects of Flavonoid-Rich Common and Tartary Buckwheat Sprout Extracts in Lipopolysaccharide-Stimulated RAW 264.7 and Peritoneal Macrophages

Directory of Open Access Journals (Sweden)

Tae Gyu Nam

2017-01-01

Full Text Available Buckwheat sprouts have been widely consumed all around world due to their great abundance of bioactive compounds. In this study, the anti-inflammatory effects of flavonoid-rich common buckwheat sprout (CBS and tartary buckwheat sprout (TBS extracts were evaluated in lipopolysaccharide- (LPS- stimulated RAW 264.7 murine macrophages and primary peritoneal macrophages from male BALB/c mice. Based on the reversed-phase HPLC analysis, the major flavonoids in CBS were determined to be C-glycosylflavones (orientin, isoorientin, vitexin, and isovitexin, quercetin-3-O-robinobioside, and rutin, whereas TBS contained only high amounts of rutin. The TBS extract exhibited higher inhibitory activity as assessed by the production of proinflammatory mediators such as nitric oxide and cytokines including tumor necrosis factor-α, interleukin- (IL- 6, and IL-12 in LPS-stimulated RAW 264.7 macrophages than CBS extract. In addition, TBS extract suppressed nuclear factor-kappa B activation by preventing inhibitor kappa B-alpha degradation and mitogen-activated protein kinase phosphorylation in LPS-stimulated RAW 264.7 macrophages. Moreover, the TBS extract markedly reduced LPS-induced cytokine production in peritoneal macrophages. Taken together, these findings suggest that TBS extract can be a potential source of anti-inflammatory agents that may influence macrophage-mediated inflammatory disorders.

Arachidonic acid triggers an oxidative burst in leukocytes

Directory of Open Access Journals (Sweden)

Pompeia C.

2003-01-01

Full Text Available The change in cellular reducing potential, most likely reflecting an oxidative burst, was investigated in arachidonic acid- (AA stimulated leukocytes. The cells studied included the human leukemia cell lines HL-60 (undifferentiated and differentiated into macrophage-like and polymorphonuclear-like cells, Jurkat and Raji, and thymocytes and macrophages from rat primary cultures. The oxidative burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative burst until an optimum AA concentration was reached and the burst decreased thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to 400 µM (up to 16-fold, whereas in rat cells it varied from 10 to 20 µM. Initial rates of superoxide generation were high, decreasing steadily and ceasing about 2 h post-treatment. The continuous presence of AA was not needed to stimulate superoxide generation. It seems that the NADPH oxidase system participates in AA-stimulated superoxide production in these cells since the oxidative burst was stimulated by NADPH and inhibited by N-ethylmaleimide, diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the oxidative burst may be due to its detergent action. There apparently was no contribution of other superoxide-generating systems such as xanthine-xanthine oxidase, cytochromes P-450 and mitochondrial electron transport chain, as assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem to interfere with the AA-stimulated oxidative burst since there was no systematic effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but lipid peroxides may play a role, as indicated by the inhibition of nitroblue tetrazolium reduction promoted by tocopherol.

Preliminary failure modes and effects analysis on Korean HCCR TBS to be tested in ITER

International Nuclear Information System (INIS)

Ahn, Mu-Young; Cho, Seungyon; Jin, Hyung Gon; Lee, Dong Won; Park, Yi-Hyun; Lee, Youngmin

2015-01-01

Highlights: • Postulated initiating events are identified through failure modes and effects analysis on the current HCCR TBS design. • A set of postulated initiating events are selected for consideration of deterministic analysis. • Accident evolutions on the selected postualted initiating events are qualitatively described for deterministic analysis. - Abstract: Korean Helium cooled ceramic reflector (HCCR) Test blanket system (TBS), which comprises Test blanket module (TBM) and ancillary systems in various locations of ITER building, is operated at high temperature and pressure with decay heat. Therefore, safety is utmost concern in design process and it is required to demonstrate that the HCCR TBS is designed to comply with the safety requirements and guidelines of ITER. Due to complexity of the system with many interfaces with ITER, a systematic approach is necessary for safety analysis. This paper presents preliminary failure modes and effects analysis (FMEA) study performed for the HCCR TBS. FMEA is a systematic methodology in which failure modes for components in the system and their consequences are studied from the bottom-up. Over eighty failure modes have been investigated on the HCCR TBS. The failure modes that have similar consequences are grouped as postulated initiating events (PIEs) and total seven reference accident scenarios are derived from FMEA study for deterministic accident analysis. Failure modes not covered here due to evolving design of the HCCR TBS and uncertainty in maintenance procedures will be studied further in near future.

Preliminary failure modes and effects analysis on Korean HCCR TBS to be tested in ITER

Energy Technology Data Exchange (ETDEWEB)

Ahn, Mu-Young, E-mail: myahn74@nfri.re.kr [National Fusion Research Institute, Daejeon (Korea, Republic of); Cho, Seungyon [National Fusion Research Institute, Daejeon (Korea, Republic of); Jin, Hyung Gon; Lee, Dong Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Park, Yi-Hyun; Lee, Youngmin [National Fusion Research Institute, Daejeon (Korea, Republic of)

2015-10-15

Highlights: • Postulated initiating events are identified through failure modes and effects analysis on the current HCCR TBS design. • A set of postulated initiating events are selected for consideration of deterministic analysis. • Accident evolutions on the selected postualted initiating events are qualitatively described for deterministic analysis. - Abstract: Korean Helium cooled ceramic reflector (HCCR) Test blanket system (TBS), which comprises Test blanket module (TBM) and ancillary systems in various locations of ITER building, is operated at high temperature and pressure with decay heat. Therefore, safety is utmost concern in design process and it is required to demonstrate that the HCCR TBS is designed to comply with the safety requirements and guidelines of ITER. Due to complexity of the system with many interfaces with ITER, a systematic approach is necessary for safety analysis. This paper presents preliminary failure modes and effects analysis (FMEA) study performed for the HCCR TBS. FMEA is a systematic methodology in which failure modes for components in the system and their consequences are studied from the bottom-up. Over eighty failure modes have been investigated on the HCCR TBS. The failure modes that have similar consequences are grouped as postulated initiating events (PIEs) and total seven reference accident scenarios are derived from FMEA study for deterministic accident analysis. Failure modes not covered here due to evolving design of the HCCR TBS and uncertainty in maintenance procedures will be studied further in near future.

Correlation between the sudden jump-like increases of the atrio-Hisian interval induced during burst atrial pacing and during programmed atrial stimulation in patients with atrioventricular nodal reentrant tachycardia.

Science.gov (United States)

Bayraktarova, Iskra H; Stoyanov, Milko K; Kunev, Boyan T; Shalganov, Tchavdar N

To study the correlation between the sudden prolongations of the atrio-Hisian (AH) interval with ≥50 ms during burst and programmed atrial stimulation, and to define whether the AH jump during burst atrial pacing is a reliable diagnostic criterion for dual AV nodal physiology. Retrospective data on 304 patients with preliminary ECG diagnosis of AV nodal reentrant tachycardia (AVNRT), confirmed during electrophysiological study, was analyzed for the presence of AH jump during burst and programmed atrial stimulation, and for correlation between the pacing modes for inducing the jump. Wilcoxon signed-ranks test and Spearman's bivariate correlation coefficient were applied, significant was P-value jump occurred during burst atrial pacing in 81% of the patients, and during programmed stimulation - in 78%, P = 0.366. In 63.2% AH jump was induced by both pacing modes; in 17.8% - only by burst pacing; in 14.8% - only by programmed pacing; in 4.2% there was no inducible jump. There was negative correlation between both pacing modes, ρ = -0.204, Р<0.001. Burst and programmed atrial stimulation separately prove the presence of dual AV nodal physiology in 81 and 78% of the patients with AVNRT, respectively. There is negative correlation between the two pacing modes, allowing the combination of the two methods to prove diagnostic in 95.8% of the patients. Copyright © 2017 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

Improved discrimination of visual stimuli following repetitive transcranial magnetic stimulation.

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Michael L Waterston

Full Text Available BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a "virtual lesion" in stimulated brain regions, with correspondingly diminished behavioral performance. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effects of rTMS to visual cortex on subjects' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task. CONCLUSIONS/SIGNIFICANCE: Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception.

Pre-stimulus thalamic theta power predicts human memory formation.

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Sweeney-Reed, Catherine M; Zaehle, Tino; Voges, Jürgen; Schmitt, Friedhelm C; Buentjen, Lars; Kopitzki, Klaus; Richardson-Klavehn, Alan; Hinrichs, Hermann; Heinze, Hans-Jochen; Knight, Robert T; Rugg, Michael D

2016-09-01

Pre-stimulus theta (4-8Hz) power in the hippocampus and neocortex predicts whether a memory for a subsequent event will be formed. Anatomical studies reveal thalamus-hippocampal connectivity, and lesion, neuroimaging, and electrophysiological studies show that memory processing involves the dorsomedial (DMTN) and anterior thalamic nuclei (ATN). The small size and deep location of these nuclei have limited real-time study of their activity, however, and it is unknown whether pre-stimulus theta power predictive of successful memory formation is also found in these subcortical structures. We recorded human electrophysiological data from the DMTN and ATN of 7 patients receiving deep brain stimulation for refractory epilepsy. We found that greater pre-stimulus theta power in the right DMTN was associated with successful memory encoding, predicting both behavioral outcome and post-stimulus correlates of successful memory formation. In particular, significant correlations were observed between right DMTN theta power and both frontal theta and right ATN gamma (32-50Hz) phase alignment, and frontal-ATN theta-gamma cross-frequency coupling. We draw the following primary conclusions. Our results provide direct electrophysiological evidence in humans of a role for the DMTN as well as the ATN in memory formation. Furthermore, prediction of subsequent memory performance by pre-stimulus thalamic oscillations provides evidence that post-stimulus differences in thalamic activity that index successful and unsuccessful encoding reflect brain processes specifically underpinning memory formation. Finally, the findings broaden the understanding of brain states that facilitate memory encoding to include subcortical as well as cortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

Ketamine blocks bursting in the lateral habenula to rapidly relieve depression.

Science.gov (United States)

Yang, Yan; Cui, Yihui; Sang, Kangning; Dong, Yiyan; Ni, Zheyi; Ma, Shuangshuang; Hu, Hailan

2018-02-14

The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants.

A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activation.

Science.gov (United States)

Liu, Yan; Wang, Yubin; Zhu, Guoqi; Sun, Jiandong; Bi, Xiaoning; Baudry, Michel

2016-06-01

While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

1.28-Tb/s Demultiplexing of an OTDM DPSK Data Signal Using a Silicon Waveguide

DEFF Research Database (Denmark)

Ji, Hua; Galili, Michael; Hu, Hao

2010-01-01

This letter demonstrates optical demultiplexing of a 1.28-Tb/s serial differential phase-shift-keying data signal using a nano-engineered silicon waveguide. We first present error-free performance at 640 Gb/s and then at 1.28 Tb/s with characterization of all 128 channels. Bit-error rates below $10...

Synaptic plasticity and spatial working memory are impaired in the CD mouse model of Williams-Beuren syndrome.

Science.gov (United States)

Borralleras, Cristina; Mato, Susana; Amédée, Thierry; Matute, Carlos; Mulle, Christophe; Pérez-Jurado, Luis A; Campuzano, Victoria

2016-08-02

Mice heterozygous for a complete deletion (CD) equivalent to the most common deletion found in individuals with Williams-Beuren syndrome (WBS) recapitulate relevant features of the neurocognitive phenotype, such as hypersociability, along with some neuroanatomical alterations in specific brain areas. However, the pathophysiological mechanisms underlying these phenotypes still remain largely unknown. We have studied the synaptic function and cognition in CD mice using hippocampal slices and a behavioral test sensitive to hippocampal function. We have found that long-term potentiation (LTP) elicited by theta burst stimulation (TBS) was significantly impaired in hippocampal field CA1 of CD animals. This deficit might be associated with the observed alterations in spatial working memory. However, we did not detect changes in presynaptic function, LTP induction mechanisms or AMPA and NMDA receptor function. Reduced levels of Brain-derived neurotrophic factor (BDNF) were present in the CA1-CA3 hippocampal region of CD mice, which could account for LTP deficits in these mice. Taken together, these results suggest a defect of CA1 synapses in CD mice to sustain synaptic strength after stimulation. These data represent the first description of synaptic functional deficits in CD mice and further highlights the utility of the CD model to study the mechanisms underlying the WBS neurocognitive profile.

A re-examination of Hebbian-covariance rules and spike timing-dependent plasticity in cat visual cortex in vivo

Directory of Open Access Journals (Sweden)

Yves Frégnac

2010-12-01

Full Text Available Spike-Timing-Dependent Plasticity (STDP is considered as an ubiquitous rule for associative plasticity in cortical networks in vitro. However, limited supporting evidence for its functional role has been provided in vivo. In particular, there are very few studies demonstrating the co-occurence of synaptic efficiency changes and alteration of sensory responses in adult cortex during Hebbian or STDP protocols. We addressed this issue by reviewing and comparing the functional effects of two types of cellular conditioning in cat visual cortex. The first one, referred to as the covariance protocol, obeys a generalized Hebbian framework, by imposing, for different stimuli, supervised positive and negative changes in covariance between postsynaptic and presynaptic activity rates. The second protocol, based on intracellular recordings, replicated in vivo variants of the theta-burst paradigm (TBS, proven successful in inducing long-term potentiation (LTP in vitro. Since it was shown to impose a precise correlation delay between the electrically activated thalamic input and the TBS-induced postsynaptic spike, this protocol can be seen as a probe of causal (pre-before-post STDP. By choosing a thalamic region where the visual field representation was in retinotopic overlap with the intracellularly recorded cortical receptive field as the afferent site for supervised electrical stimulation, this protocol allowed to look for possible correlates between STDP and functional reorganization of the conditioned cortical receptive field. The rate-based covariance protocol induced significant and large amplitude changes in receptive field properties, in both kitten and adult V1 cortex. The TBS STDP-like protocol produced in the adult significant changes in the synaptic gain of the electrically activated thalamic pathway, but the statistical significance of the functional correlates was detectable mostly at the population level. Comparison of our observations with the

Preliminary result on trabecular bone score (TBS in lumbar vertebrae with experimentally altered microarchitecture

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M. Di Stefano

2013-01-01

Full Text Available The aim of this preliminary research is to investigate the reliability of a new qualitative parameter, called Trabecular Bone Score (TBS, recently proposed for evaluating the microarchitectural arrangement of cancellous bone in scans carried out by dual energy X-ray absorptiometry (DXA. Vertebral bodies of 15 fresh samples of lumbar spines of adult pig were analysed either in basal conditions and with altered microarchitecture of the cancellous bone obtained by progressive drilling. The examined bony areas do not show changes in bone mineral density (BMD, whereas TBS values decrease with the increasing alteration of the vertebral microtrabecular structure. Our preliminary data seem to confirm the reliability of TBS as a qualitative parameter useful for evaluating the microarchitectural strength in bony areas quantitatively analysed by DXA.

Design of a 1 Tb/s superchannel coherent receiver

NARCIS (Netherlands)

Millar, D.S.; Maher, R.; Lavery, D.; Koike-Akino, T.; Pajovic, M.; Alvarado, A.; Paskov, M.; Kojima, K.; Parsons, K.; Thomsen, B.C.; Savory, S.J.; Bayvel, P.

2016-01-01

We describe the design of a trained and pilot-aided digital coherent receiver, capable of detecting a 1 Tb/s superchannel with a single optical front-end. Algorithms for receiver training are described, which calculate the equalizer coefficients, subchannel SNRs, and centroids of the transmitted

Phase-locking of bursting neuronal firing to dominant LFP frequency components.

Science.gov (United States)

Constantinou, Maria; Elijah, Daniel H; Squirrell, Daniel; Gigg, John; Montemurro, Marcelo A

2015-10-01

Neuronal firing in the hippocampal formation relative to the phase of local field potentials (LFP) has a key role in memory processing and spatial navigation. Firing can be in either tonic or burst mode. Although bursting neurons are common in the hippocampal formation, the characteristics of their locking to LFP phase are not completely understood. We investigated phase-locking properties of bursting neurons using simulations generated by a dual compartmental model of a pyramidal neuron adapted to match the bursting activity in the subiculum of a rat. The model was driven with stochastic input signals containing a power spectral profile consistent with physiologically relevant frequencies observed in LFP. The single spikes and spike bursts fired by the model were locked to a preferred phase of the predominant frequency band where there was a peak in the power of the driving signal. Moreover, the preferred phase of locking shifted with increasing burst size, providing evidence that LFP phase can be encoded by burst size. We also provide initial support for the model results by analysing example data of spontaneous LFP and spiking activity recorded from the subiculum of a single urethane-anaesthetised rat. Subicular neurons fired single spikes, two-spike bursts and larger bursts that locked to a preferred phase of either dominant slow oscillations or theta rhythms within the LFP, according to the model prediction. Both power-modulated phase-locking and gradual shift in the preferred phase of locking as a function of burst size suggest that neurons can use bursts to encode timing information contained in LFP phase into a spike-count code. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A conceptual lemon: theta burst stimulation to the left anterior temporal lobe untangles object representation and its canonical color.

Science.gov (United States)

Chiou, Rocco; Sowman, Paul F; Etchell, Andrew C; Rich, Anina N

2014-05-01

Object recognition benefits greatly from our knowledge of typical color (e.g., a lemon is usually yellow). Most research on object color knowledge focuses on whether both knowledge and perception of object color recruit the well-established neural substrates of color vision (the V4 complex). Compared with the intensive investigation of the V4 complex, we know little about where and how neural mechanisms beyond V4 contribute to color knowledge. The anterior temporal lobe (ATL) is thought to act as a "hub" that supports semantic memory by integrating different modality-specific contents into a meaningful entity at a supramodal conceptual level, making it a good candidate zone for mediating the mappings between object attributes. Here, we explore whether the ATL is critical for integrating typical color with other object attributes (object shape and name), akin to its role in combining nonperceptual semantic representations. In separate experimental sessions, we applied TMS to disrupt neural processing in the left ATL and a control site (the occipital pole). Participants performed an object naming task that probes color knowledge and elicits a reliable color congruency effect as well as a control quantity naming task that also elicits a cognitive congruency effect but involves no conceptual integration. Critically, ATL stimulation eliminated the otherwise robust color congruency effect but had no impact on the numerical congruency effect, indicating a selective disruption of object color knowledge. Neither color nor numerical congruency effects were affected by stimulation at the control occipital site, ruling out nonspecific effects of cortical stimulation. Our findings suggest that the ATL is involved in the representation of object concepts that include their canonical colors.

Bursts of occipital theta and alpha amplitude preceding alternation and repetition trials in a task-switching experiment

NARCIS (Netherlands)

Gladwin, T.E.; De Jong, Ritske

The instantaneous amplitude of the theta and alpha bands of the electroencephalogram (EEG) was studied during preparation periods in a task-switching experiment. Subjects had to switch between tasks in which they were to respond to either the visual or the auditory component of the stimulus. 11-13

Visual attentional load influences plasticity in the human motor cortex.

Science.gov (United States)

Kamke, Marc R; Hall, Michelle G; Lye, Hayley F; Sale, Martin V; Fenlon, Laura R; Carroll, Timothy J; Riek, Stephan; Mattingley, Jason B

2012-05-16

Neural plasticity plays a critical role in learning, memory, and recovery from injury to the nervous system. Although much is known about the physical and physiological determinants of plasticity, little is known about the influence of cognitive factors. In this study, we investigated whether selective attention plays a role in modifying changes in neural excitability reflecting long-term potentiation (LTP)-like plasticity. We induced LTP-like effects in the hand area of the human motor cortex using transcranial magnetic stimulation (TMS). During the induction of plasticity, participants engaged in a visual detection task with either low or high attentional demands. Changes in neural excitability were assessed by measuring motor-evoked potentials in a small hand muscle before and after the TMS procedures. In separate experiments plasticity was induced either by paired associative stimulation (PAS) or intermittent theta-burst stimulation (iTBS). Because these procedures induce different forms of LTP-like effects, they allowed us to investigate the generality of any attentional influence on plasticity. In both experiments reliable changes in motor cortex excitability were evident under low-load conditions, but this effect was eliminated under high-attentional load. In a third experiment we investigated whether the attentional task was associated with ongoing changes in the excitability of motor cortex, but found no difference in evoked potentials across the levels of attentional load. Our findings indicate that in addition to their role in modifying sensory processing, mechanisms of attention can also be a potent modulator of cortical plasticity.

Optogenetic stimulation effectively enhances intrinsically generated network synchrony

Science.gov (United States)

El Hady, Ahmed; Afshar, Ghazaleh; Bröking, Kai; Schlüter, Oliver M.; Geisel, Theo; Stühmer, Walter; Wolf, Fred

2013-01-01

Synchronized bursting is found in many brain areas and has also been implicated in the pathophysiology of neuropsychiatric disorders such as epilepsy, Parkinson’s disease, and schizophrenia. Despite extensive studies of network burst synchronization, it is insufficiently understood how this type of network wide synchronization can be strengthened, reduced, or even abolished. We combined electrical recording using multi-electrode array with optical stimulation of cultured channelrhodopsin-2 transducted hippocampal neurons to study and manipulate network burst synchronization. We found low frequency photo-stimulation protocols that are sufficient to induce potentiation of network bursting, modifying bursting dynamics, and increasing interneuronal synchronization. Surprisingly, slowly fading-in light stimulation, which substantially delayed and reduced light-driven spiking, was at least as effective in reorganizing network dynamics as much stronger pulsed light stimulation. Our study shows that mild stimulation protocols that do not enforce particular activity patterns onto the network can be highly effective inducers of network-level plasticity. PMID:24155695

Optogenetic stimulation effectively enhances intrinsically generated network synchrony

Directory of Open Access Journals (Sweden)

Ahmed eEl Hady

2013-10-01

Full Text Available Synchronized bursting is found in many brain areas and has also been implicated in the pathophysiology of neuropsychiatric disorders such as epilepsy, Parkinson’s disease and schizophrenia. Despite extensive studies of network burst synchronization, it is insufficiently understood how this type of network wide synchronization can be strengthened, reduced or even abolished. We combined electrical recording using multi-electrode array with optical stimulation of cultured channelrhodopsin-2 transducted hippocampal neurons to study and manipulate network burst synchronization. We found low frequency photo-stimulation protocols that are sufficient to induce potentiation of network bursting, modifying bursting dynamics and increasing interneuronal synchronization. Surprisingly, slowly fading-in light stimulation, which substantially delayed and reduced light driven spiking, was at least as effective in reorganizing network dynamics as much stronger pulsed light stimulation. Our study shows that mild stimulation protocols that do not enforce particular activity patterns onto the network can be highly effective inducers of network-level plasticity.

Dynamic encoding of natural luminance sequences by LGN bursts.

Directory of Open Access Journals (Sweden)

Nicholas A Lesica

2006-07-01

Full Text Available In the lateral geniculate nucleus (LGN of the thalamus, visual stimulation produces two distinct types of responses known as tonic and burst. Due to the dynamics of the T-type Ca(2+ channels involved in burst generation, the type of response evoked by a particular stimulus depends on the resting membrane potential, which is controlled by a network of modulatory connections from other brain areas. In this study, we use simulated responses to natural scene movies to describe how modulatory and stimulus-driven changes in LGN membrane potential interact to determine the luminance sequences that trigger burst responses. We find that at low resting potentials, when the T channels are de-inactivated and bursts are relatively frequent, an excitatory stimulus transient alone is sufficient to evoke a burst. However, to evoke a burst at high resting potentials, when the T channels are inactivated and bursts are relatively rare, prolonged inhibitory stimulation followed by an excitatory transient is required. We also observe evidence of these effects in vivo, where analysis of experimental recordings demonstrates that the luminance sequences that trigger bursts can vary dramatically with the overall burst percentage of the response. To characterize the functional consequences of the effects of resting potential on burst generation, we simulate LGN responses to different luminance sequences at a range of resting potentials with and without a mechanism for generating bursts. Using analysis based on signal detection theory, we show that bursts enhance detection of specific luminance sequences, ranging from the onset of excitatory sequences at low resting potentials to the offset of inhibitory sequences at high resting potentials. These results suggest a dynamic role for burst responses during visual processing that may change according to behavioral state.

Enhancement of multitasking performance and neural oscillations by transcranial alternating current stimulation.

Science.gov (United States)

Hsu, Wan-Yu; Zanto, Theodore P; van Schouwenburg, Martine R; Gazzaley, Adam

2017-01-01

Multitasking is associated with the generation of stimulus-locked theta (4-7 Hz) oscillations arising from prefrontal cortex (PFC). Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that influences endogenous brain oscillations. Here, we investigate whether applying alternating current stimulation within the theta frequency band would affect multitasking performance, and explore tACS effects on neurophysiological measures. Brief runs of bilateral PFC theta-tACS were applied while participants were engaged in a multitasking paradigm accompanied by electroencephalography (EEG) data collection. Unlike an active control group, a tACS stimulation group showed enhancement of multitasking performance after a 90-minute session (F1,35 = 6.63, p = 0.01, ηp2 = 0.16; effect size = 0.96), coupled with significant modulation of posterior beta (13-30 Hz) activities (F1,32 = 7.66, p = 0.009, ηp2 = 0.19; effect size = 0.96). Across participant regression analyses indicated that those participants with greater increases in frontal theta, alpha and beta oscillations exhibited greater multitasking performance improvements. These results indicate frontal theta-tACS generates benefits on multitasking performance accompanied by widespread neuronal oscillatory changes, and suggests that future tACS studies with extended treatments are worth exploring as promising tools for cognitive enhancement.

Enhancement of multitasking performance and neural oscillations by transcranial alternating current stimulation.

Directory of Open Access Journals (Sweden)

Wan-Yu Hsu

Full Text Available Multitasking is associated with the generation of stimulus-locked theta (4-7 Hz oscillations arising from prefrontal cortex (PFC. Transcranial alternating current stimulation (tACS is a non-invasive brain stimulation technique that influences endogenous brain oscillations. Here, we investigate whether applying alternating current stimulation within the theta frequency band would affect multitasking performance, and explore tACS effects on neurophysiological measures. Brief runs of bilateral PFC theta-tACS were applied while participants were engaged in a multitasking paradigm accompanied by electroencephalography (EEG data collection. Unlike an active control group, a tACS stimulation group showed enhancement of multitasking performance after a 90-minute session (F1,35 = 6.63, p = 0.01, ηp2 = 0.16; effect size = 0.96, coupled with significant modulation of posterior beta (13-30 Hz activities (F1,32 = 7.66, p = 0.009, ηp2 = 0.19; effect size = 0.96. Across participant regression analyses indicated that those participants with greater increases in frontal theta, alpha and beta oscillations exhibited greater multitasking performance improvements. These results indicate frontal theta-tACS generates benefits on multitasking performance accompanied by widespread neuronal oscillatory changes, and suggests that future tACS studies with extended treatments are worth exploring as promising tools for cognitive enhancement.

Long-term potentiation in hilar circuitry modulates gating by the dentate gyrus.

Science.gov (United States)

Wright, Brandon J; Jackson, Meyer B

2014-07-16

The dentate gyrus serves as a gateway to the hippocampus, filtering and processing sensory inputs as an animal explores its environment. The hilus occupies a strategic position within the dentate gyrus from which it can play a pivotal role in these functions. Inputs from dentate granule cells converge on the hilus, and excitatory hilar mossy cells redistribute these signals back to granule cells to transform a pattern of cortical input into a new pattern of output to the hippocampal CA3 region. Using voltage-sensitive dye to image electrical activity in rat hippocampal slices, we explored how long-term potentiation (LTP) of different excitatory synapses modifies the flow of information. Theta burst stimulation of the perforant path potentiated responses throughout the molecular layer, but left responses in the CA3 region unchanged. By contrast, theta burst stimulation of the granule cell layer potentiated responses throughout the molecular layer, as well as in the CA3 region. Theta burst stimulation of the granule cell layer potentiated CA3 responses not only to granule cell layer stimulation but also to perforant path stimulation. Potentiation of responses in the CA3 region reflected NMDA receptor-dependent LTP of upstream synapses between granule cells and mossy cells, with no detectable contribution from NMDA receptor-independent LTP of local CA3 mossy fiber synapses. Potentiation of transmission to the CA3 region required LTP in both granule cell→mossy cell and mossy cell→granule cell synapses. This bidirectional plasticity enables hilar circuitry to regulate the flow of information through the dentate gyrus and on to the hippocampus. Copyright © 2014 the authors 0270-6474/14/349743-11$15.00/0.

Cortical theta wanes for language.

Science.gov (United States)

Hermes, Dora; Miller, Kai J; Vansteensel, Mariska J; Edwards, Erik; Ferrier, Cyrille H; Bleichner, Martin G; van Rijen, Peter C; Aarnoutse, Erik J; Ramsey, Nick F

2014-01-15

The role of low frequency oscillations in language areas is not yet understood. Using ECoG in six human subjects, we studied whether different language regions show prominent power changes in a specific rhythm, in similar manner as the alpha rhythm shows the most prominent power changes in visual areas. Broca's area and temporal language areas were localized in individual subjects using fMRI. In these areas, the theta rhythm showed the most pronounced power changes and theta power decreased significantly during verb generation. To better understand the role of this language-related theta decrease, we then studied the interaction between low frequencies and local neuronal activity reflected in high frequencies. Amplitude-amplitude correlations showed that theta power correlated negatively with high frequency activity, specifically across verb generation trials. Phase-amplitude coupling showed that during control trials, high frequency power was coupled to theta phase, but this coupling decreased significantly during verb generation trials. These results suggest a dynamic interaction between the neuronal mechanisms underlying the theta rhythm and local neuronal activity in language areas. As visual areas show a pronounced alpha rhythm that may reflect pulsed inhibition, language regions show a pronounced theta rhythm with highly similar features. © 2013.

{theta}-Compactness in L-topological spaces

Energy Technology Data Exchange (ETDEWEB)

Hanafy, I.M. [Department of Mathematics, Faculty of Education, Suez Canal University, El-Arish (Egypt)], E-mail: ihanafy@hotmail.com

2009-12-15

Recently, El-Naschie has shown that the notion of fuzzy topology may be relevant to quantum particle physics in connection with string theory and e{sup {infinity}} theory. In 2005, Caldas and Jafari have introduced {theta}-compact fuzzy topological spaces. In this paper, the concepts of{theta}-compactness, countable{theta}-compactness and the{theta}-Lindeloef property are introduced and studied in L-topological spaces, where L is a complete de Morgan algebra. They are defined by means of{theta}-openL-sets and their inequalities. They does not rely on the structure of basis lattice L and no distributivity in L is required. They can also be characterized by{theta}-closedL-sets and their inequalities. When L is a completely de Morgan algebra, their many characterizations are presented.

Dynamics of ponderomotive self-focusing and periodic bursts of stimulated Brillouin backscattering in plasmas

International Nuclear Information System (INIS)

Andreev, N.E.; Gorbunov, L.M.; Tarakanov, S.V.; Zykov, A.I.

1993-01-01

The space--time evolution of ponderomotive self-focusing of electromagnetic beams in a plasma is investigated. The quasineutral, hydrodynamic plasma response to the ponderomotive force is considered. The set of coupled quasioptic and acoustic equations is solved both analytically and numerically for slab and cylindrical beams. It is shown that the transient process of self-focusing has the form of a nonlinear wave propagating along the beam axis from boundary into the interior of a plasma with velocity considerably higher than the ion-sound velocity. Mutual dynamics of self-focusing and stimulated Brillouin backscattering (SBBS) is computed. It is shown that self-focusing results in the high intensity periodical bursts of SBBS. However, the time average level of scattered radiation is quite low

TBS - veroordeeld tot vooroordeel: een visie na analyse van historische fundamenten van recente knelpunten, het systeem en buitenlandse alternatieven

NARCIS (Netherlands)

M.J.F. van der Wolf (Michiel)

2012-01-01

textabstractIn 2005 there was a re-offense by a TBS (Dutch entrustment) patient on leave, which lead to upheaval in society and a parliamentary inquiry commission into the TBS-system, which reported in 2006. This trend of continuing changes in policy and legislation since the last major revision of

Het belang van beschermende factoren in de risicotaxatie van tbs-gestelden

NARCIS (Netherlands)

Nagtegaal, M.H.; Schönberger, H.J.M.

2013-01-01

In dit onderzoek staan de volgende vragen centraal: Is het meenemen van beschermende factoren van toegevoegde waarde voor de risicotaxatie zoals deze plaatsvindt in de tbs-praktijk? Zo ja, op welke manier? Hierbij wordt onder ander het belang van beschermende factoren voor de behandelpraktijk en de

Theta rhythm-like bidirectional cycling dynamics of living neuronal networks in vitro.

Science.gov (United States)

Gladkov, Arseniy; Grinchuk, Oleg; Pigareva, Yana; Mukhina, Irina; Kazantsev, Victor; Pimashkin, Alexey

2018-01-01

The phenomena of synchronization, rhythmogenesis and coherence observed in brain networks are believed to be a dynamic substrate for cognitive functions such as learning and memory. However, researchers are still debating whether the rhythmic activity emerges from the network morphology that developed during neurogenesis or as a result of neuronal dynamics achieved under certain conditions. In the present study, we observed self-organized spiking activity that converged to long, complex and rhythmically repeated superbursts in neural networks formed by mature hippocampal cultures with a high cellular density. The superburst lasted for tens of seconds and consisted of hundreds of short (50-100 ms) small bursts with a high spiking rate of 139.0 ± 78.6 Hz that is associated with high-frequency oscillations in the hippocampus. In turn, the bursting frequency represents a theta rhythm (11.2 ± 1.5 Hz). The distribution of spikes within the bursts was non-random, representing a set of well-defined spatio-temporal base patterns or motifs. The long superburst was classified into two types. Each type was associated with a unique direction of spike propagation and, hence, was encoded by a binary sequence with random switching between the two "functional" states. The precisely structured bidirectional rhythmic activity that developed in self-organizing cultured networks was quite similar to the activity observed in the in vivo experiments.

Theta rhythm-like bidirectional cycling dynamics of living neuronal networks in vitro.

Directory of Open Access Journals (Sweden)

Arseniy Gladkov

Full Text Available The phenomena of synchronization, rhythmogenesis and coherence observed in brain networks are believed to be a dynamic substrate for cognitive functions such as learning and memory. However, researchers are still debating whether the rhythmic activity emerges from the network morphology that developed during neurogenesis or as a result of neuronal dynamics achieved under certain conditions. In the present study, we observed self-organized spiking activity that converged to long, complex and rhythmically repeated superbursts in neural networks formed by mature hippocampal cultures with a high cellular density. The superburst lasted for tens of seconds and consisted of hundreds of short (50-100 ms small bursts with a high spiking rate of 139.0 ± 78.6 Hz that is associated with high-frequency oscillations in the hippocampus. In turn, the bursting frequency represents a theta rhythm (11.2 ± 1.5 Hz. The distribution of spikes within the bursts was non-random, representing a set of well-defined spatio-temporal base patterns or motifs. The long superburst was classified into two types. Each type was associated with a unique direction of spike propagation and, hence, was encoded by a binary sequence with random switching between the two "functional" states. The precisely structured bidirectional rhythmic activity that developed in self-organizing cultured networks was quite similar to the activity observed in the in vivo experiments.

HCCR TBS LOCA and ICE into small confined volume

International Nuclear Information System (INIS)

Jin, Hyung Gon; Ahn, Mu-Young

2016-01-01

KAERI has participated in the development of HCCR (Helium Cooled Ceramic Reflector) TBS (Test Blanket System) as a member of the KO TBM Team. Conceptual design review of this system had been performed in 2015 and after resolving the chits, the final approval was achieved in March 2016. This safety issue is one of the category II chits in the CDR and resolution strategy was already approved, however, safety analysis should be done until PDR (Preliminary Design Review). In this paper, model and nodalization for the accident are given and preliminary result is included. Nominal design pressure of HCS loop is 8 MPa, therefore, as indicated in the figure below. During the break of cooling pipe between TBM and Shield, the high pressure coolant will ingress to the 'interspace' between TBM, Shield and Frame. The coolant will be released through the front gaps between TBM and Frame towards VV primary vacuum. Accident analysis about HCCR TBS LOCA and ICE into small confined volume has been done successfully. Inverspace volume is compatibly small volume for 8MPa helium loop rupture, which causes fast pressure build-up the space but it decrease within 10 seconds. It is expected that other type of TBM has almost the same behavior

Qualification test for ITER HCCR-TBS mockups with high heat flux test facility

Energy Technology Data Exchange (ETDEWEB)

Kim, Suk-Kwon, E-mail: skkim93@kaeri.re.kr [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Park, Seong Dae; Jin, Hyung Gon; Lee, Eo Hwak; Yoon, Jae-Sung; Lee, Dong Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cho, Seungyon [National Fusion Research Institute, Daejeon (Korea, Republic of)

2016-11-01

Highlights: • The test mockups for ITER HCCR (Helium Cooled Ceramic Reflector) TBS (Test Blanket System) in Korea were designed and fabricated. • A thermo-hydraulic analysis was performed using a high heat flux test facility by using electron beam. • The plan for qualification tests was developed to evaluate the thermo-hydraulic efficiency in accordance with the requirements of the ITER Organization. - Abstract: The test mockups for ITER HCCR (Helium Cooled Ceramic Reflector) TBS (Test Blanket System) in Korea were designed and fabricated, and an integrity and thermo-hydraulic performance test should be completed under the same or similar operation conditions of ITER. The test plan for a thermo-hydraulic analysis was developed by using a high heat flux test facility, called the Korean heat load test facility by using electron beam (KoHLT-EB). This facility is utilized for a qualification test of the plasma facing component (PFC) for the ITER first wall and DEMO divertor, and for the thermo-hydraulic experiments. In this work, KoHLT-EB will be used for the plan of the performance qualification test of the ITER HCCR-TBS mockups. This qualification tests should be performed to evaluate the thermo-hydraulic efficiency in accordance with the requirements of the ITER Organization (IO), which describe the specifications and qualifications of the heat flux test facility and test procedure for ITER PFC.

Traveling Theta Waves in the Human Hippocampus

Science.gov (United States)

Zhang, Honghui

2015-01-01

The hippocampal theta oscillation is strongly correlated with behaviors such as memory and spatial navigation, but we do not understand its specific functional role. One hint of theta's function came from the discovery in rodents that theta oscillations are traveling waves that allow parts of the hippocampus to simultaneously exhibit separate oscillatory phases. Because hippocampal theta oscillations in humans have different properties compared with rodents, we examined these signals directly using multielectrode recordings from neurosurgical patients. Our findings confirm that human hippocampal theta oscillations are traveling waves, but also show that these oscillations appear at a broader range of frequencies compared with rodents. Human traveling waves showed a distinctive pattern of spatial propagation such that there is a consistent phase spread across the hippocampus regardless of the oscillations' frequency. This suggests that traveling theta oscillations are important functionally in humans because they coordinate phase coding throughout the hippocampus in a consistent manner. SIGNIFICANCE STATEMENT We show for the first time in humans that hippocampal theta oscillations are traveling waves, moving along the length of the hippocampus in a posterior–anterior direction. The existence of these traveling theta waves is important for understanding hippocampal neural coding because they cause neurons at separate positions in the hippocampus to experience different theta phases simultaneously. The theta phase that a neuron measures is a key factor in how that cell represents behavioral information. Therefore, the existence of traveling theta waves indicates that, to fully understand how a hippocampal neuron represents information, it is vital to also account for that cell's location in addition to conventional measures of neural activity. PMID:26354915

Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects

Directory of Open Access Journals (Sweden)

Go-Eun Lee

2017-01-01

Full Text Available The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7. The electroencephalogram (EEG signals from nine healthy young subjects were recorded before and during acupuncture in the “closed-eye” state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2. Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6 and occipital areas (O1, O2 during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5 and other areas (frontal, parietal, and occipital. Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS.

Timing tasks synchronize cerebellar and frontal ramping activity and theta oscillations: Implications for cerebellar stimulation in diseases of impaired cognition

Directory of Open Access Journals (Sweden)

Krystal Lynn Parker

2016-01-01

Full Text Available Timing is a fundamental and highly conserved mammalian capability yet the underlying neural mechanisms are widely debated. Ramping activity of single neurons that gradually increase or decrease activity to encode the passage of time, has been speculated to predict a behaviorally relevant temporal event. Cue-evoked low-frequency activity has also been implicated in temporal processing. Ramping activity and low-frequency oscillations occur throughout the brain and could indicate a network-based approach to timing. Temporal processing requires cognitive mechanisms of working memory, attention, and reasoning which are dysfunctional in neuropsychiatric disease. Therefore, timing tasks could be used to probe cognition in animals with disease phenotypes. The medial frontal cortex and cerebellum are involved in cognition. Cerebellar stimulation has been shown to influence medial frontal activity and improve cognition in schizophrenia. However, the mechanism underlying the efficacy of cerebellar stimulation is unknown. Here we discuss how timing tasks can be used to probe cerebellar interactions with the frontal cortex and the therapeutic potential of cerebellar stimulation. The goal of this theory and hypothesis manuscript is threefold. First, we will summarize evidence indicating that in addition to motor learning, timing tasks involve cognitive processes that are present within both the cerebellum and medial frontal cortex. Second, we propose methodologies to investigate the connections between these areas in patients with Parkinson’s disease, autism, and schizophrenia. We hypothesis that cerebellar transcranial stimulation may rescue medial frontal ramping activity, theta oscillations, and timing abnormalities, thereby restoring executive function in diseases of impaired cognition. These hypotheses could inspire the use of timing tasks as biomarkers for neuronal and cognitive abnormalities in neuropsychiatric disease and promote the therapeutic

Three-dimensional ideal theta(1)/theta(2) angular transformer and its uses in fiber optics.

Science.gov (United States)

Ning, X

1988-10-01

A 3-D ideal theta(1)/theta(2) angular transformer in nonimaging optics is introduced. The axially symmetric transformer, combining a portion of a hyperbolic concentrator with two lenses, transforms an input limited Lambertian over an angle theta(1) to an output limited Lambertian over an angle theta(2) without losing throughput. This is the first known transformer with such ideal properties. Results of computer simulations of a transformer with planospherical lenses are presented. Because of its ideal angular transforming property, the transformer offers an excellent solution for power launching and fiber-fiber coupling in optical fiber systems. In principle, the theoretical maximum coupling efficiency based on radiance conservation can be achieved with this transformer. Several conceptual designs of source-fiber and fiber-fiber couplers using the transformer are given.

The Neurofilament-Derived Peptide NFL-TBS.40-63 Targets Neural Stem Cells and Affects Their Properties.

Science.gov (United States)

Lépinoux-Chambaud, Claire; Barreau, Kristell; Eyer, Joël

2016-07-01

Targeting neural stem cells (NSCs) in the adult brain represents a promising approach for developing new regenerative strategies, because these cells can proliferate, self-renew, and differentiate into new neurons, astrocytes, and oligodendrocytes. Previous work showed that the NFL-TBS.40-63 peptide, corresponding to the sequence of a tubulin-binding site on neurofilaments, can target glioblastoma cells, where it disrupts their microtubules and inhibits their proliferation. We show that this peptide targets NSCs in vitro and in vivo when injected into the cerebrospinal fluid. Although neurosphere formation was not altered by the peptide, the NSC self-renewal capacity and proliferation were reduced and were associated with increased adhesion and differentiation. These results indicate that the NFL-TBS.40-63 peptide represents a new molecular tool to target NSCs to develop new strategies for regenerative medicine and the treatment of brain tumors. In the present study, the NFL-TBS.40-63 peptide targeted neural stem cells in vitro when isolated from the subventricular zone and in vivo when injected into the cerebrospinal fluid present in the lateral ventricle. The in vitro formation of neurospheres was not altered by the peptide; however, at a high concentration of the peptide, the neural stem cell (NSC) self-renewal capacity and proliferation were reduced and associated with increased adhesion and differentiation. These results indicate that the NFL-TBS.40-63 peptide represents a new molecular tool to target NSCs to develop new strategies for regenerative medicine and the treatment of brain tumors. ©AlphaMed Press.

Theta-Generalized closed sets in fuzzy topological spaces

International Nuclear Information System (INIS)

El-Shafei, M.E.; Zakari, A.

2006-01-01

In this paper we introduce the concepts of theta-generalized closed fuzzy sets and generalized fuzzy sets in topological spaces. Furthermore, generalized fuzzy sets are extended to theta-generalized fuzzy sets. Also, we introduce the concepts of fuzzy theta-generalized continuous and fuzzy theta-generalized irresolute mappings. (author)

2 x 344 Tb/s Propagation-direction Interleaved Transmission over 1500-km MCF Enhanced by Multicarrier Full Electric-field Digital Back-propagation

DEFF Research Database (Denmark)

Kobayashi, T.; Takara, H.; Sano, A.

2013-01-01

We demonstrate 12-core fiber bidirectional long-haul transmission with sub-petabit-class capacity (2 × 344 Tb/s). Inter-core crosstalk management and multicarrier nonlinear compensation enabled the longest distance of 1500 km in SDM transmission with unidirectional capacity over 300 Tb/s....

Intrahemispheric theta rhythm desynchronization impairs working memory.

Science.gov (United States)

Alekseichuk, Ivan; Pabel, Stefanie Corinna; Antal, Andrea; Paulus, Walter

2017-01-01

There is a growing interest in large-scale connectivity as one of the crucial factors in working memory. Correlative evidence has revealed the anatomical and electrophysiological players in the working memory network, but understanding of the effective role of their connectivity remains elusive. In this double-blind, placebo-controlled study we aimed to identify the causal role of theta phase connectivity in visual-spatial working memory. The frontoparietal network was over- or de-synchronized in the anterior-posterior direction by multi-electrode, 6 Hz transcranial alternating current stimulation (tACS). A decrease in memory performance and increase in reaction time was caused by frontoparietal intrahemispheric desynchronization. According to the diffusion drift model, this originated in a lower signal-to-noise ratio, known as the drift rate index, in the memory system. The EEG analysis revealed a corresponding decrease in phase connectivity between prefrontal and parietal areas after tACS-driven desynchronization. The over-synchronization did not result in any changes in either the behavioral or electrophysiological levels in healthy participants. Taken together, we demonstrate the feasibility of manipulating multi-site large-scale networks in humans, and the disruptive effect of frontoparietal desynchronization on theta phase connectivity and visual-spatial working memory.

The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation.

Science.gov (United States)

Minjoli, Sena; Saturnino, Guilherme B; Blicher, Jakob Udby; Stagg, Charlotte J; Siebner, Hartwig R; Antunes, André; Thielscher, Axel

2017-01-01

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible. Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field "hot spots" in the cortex. However, these maxima were not substantially stronger than those seen in a healthy control. The electric field pattern induced by TMS was not substantially changed by the lesions. However, the average field strength generated by TDCS was substantially decreased. This effect occurred for both head models and even when both electrodes were distant to the lesion, caused by increased current shunting through the lesion and enlarged ventricles. Judging from the similar peak field strengths compared to the healthy

Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

Science.gov (United States)

Noohi, Fatemeh; Kinnaird, Catherine; Wood, Scott; Bloomberg, Jacob; Mulavara, Ajitkumar; Seidler, Rachael

2014-01-01

The aim of the current study was to characterize the brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit saccular Vestibular Evoked Myogenic Potentials (VEMP) (Colebatch & Halmagyi 1992; Colebatch et al. 1994). Some researchers have reported that airconducted skull tap elicits both saccular and utricle VEMPs, while being faster and less irritating for the subjects (Curthoys et al. 2009, Wackym et al., 2012). However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying the vestibular disorders related to otolith deficits. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, pre and post central gyri, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation (Bottini et al., 1994; Dieterich et al., 2003; Emri et al., 2003; Schlindwein et al., 2008; Janzen et al., 2008). Here we hypothesized that the skull tap elicits the similar pattern of cortical activity as the auditory tone burst. Subjects put on a set of MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in supine position, with eyes closed. All subjects received both forms of the stimulation, however, the order of stimulation with auditory tone burst and air-conducted skull tap was counterbalanced across subjects. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular cortex, resulting in vestibular response (Halmagyi et al., 1995). Auditory tone bursts were also delivered for comparison. To validate

Mapping the after-effects of theta burst stimulation on the human auditory cortex with functional imaging.

Science.gov (United States)

Andoh, Jamila; Zatorre, Robert J

2012-09-12

Auditory cortex pertains to the processing of sound, which is at the basis of speech or music-related processing. However, despite considerable recent progress, the functional properties and lateralization of the human auditory cortex are far from being fully understood. Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses, and represents a unique method of exploring plasticity and connectivity. It has only recently begun to be applied to understand auditory cortical function. An important issue in using TMS is that the physiological consequences of the stimulation are difficult to establish. Although many TMS studies make the implicit assumption that the area targeted by the coil is the area affected, this need not be the case, particularly for complex cognitive functions which depend on interactions across many brain regions. One solution to this problem is to combine TMS with functional Magnetic resonance imaging (fMRI). The idea here is that fMRI will provide an index of changes in brain activity associated with TMS. Thus, fMRI would give an independent means of assessing which areas are affected by TMS and how they are modulated. In addition, fMRI allows the assessment of functional connectivity, which represents a measure of the temporal coupling between distant regions. It can thus be useful not only to measure the net activity modulation induced by TMS in given locations, but also the degree to which the network properties are affected by TMS, via any observed changes in functional connectivity. Different approaches exist to combine TMS and functional imaging according to the temporal order of the methods. Functional MRI can be applied before, during, after, or both before and after TMS. Recently, some studies interleaved TMS and fMRI in order to provide online mapping of the functional changes induced by TMS. However, this

Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

Science.gov (United States)

Noohi, F.; Kinnaird, C.; Wood, S.; Bloomberg, J.; Mulavara, A.; Seidler, R.

2016-01-01

The current study characterizes brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either the vestibulo-spinal reflex (saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)), or the ocular muscle response (utricle-mediated ocular VEMP (oVEMP)). Some researchers have reported that air-conducted skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for the subjects. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying otolith-specific deficits, including gait and balance problems that astronauts experience upon returning to earth. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that skull taps elicit similar patterns of cortical activity as the auditory tone bursts, and previous vestibular imaging studies. Subjects wore bilateral MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in the supine position, with eyes closed. Subjects received both forms of the stimulation in a counterbalanced fashion. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular system, resulting in the vestibular cortical response. Auditory tone bursts were also delivered for comparison. To validate our stimulation method, we measured the ocular VEMP outside of the scanner. This measurement showed that both skull tap and auditory

Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

Science.gov (United States)

Sibonga, J. D.; Spector, E. R.; King, L. J.; Evans, H. J.; Smith, S. A.

2014-01-01

Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS

Harnessing the power of theta: natural manipulations of cognitive performance during hippocampal theta-contingent eyeblink conditioning

Science.gov (United States)

Hoffmann, Loren C.; Cicchese, Joseph J.; Berry, Stephen D.

2015-01-01

Neurobiological oscillations are regarded as essential to normal information processing, including coordination and timing of cells and assemblies within structures as well as in long feedback loops of distributed neural systems. The hippocampal theta rhythm is a 3–12 Hz oscillatory potential observed during cognitive processes ranging from spatial navigation to associative learning. The lower range, 3–7 Hz, can occur during immobility and depends upon the integrity of cholinergic forebrain systems. Several studies have shown that the amount of pre-training theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning. Our lab has used a brain-computer interface (BCI) that delivers eyeblink conditioning trials contingent upon the explicit presence or absence of hippocampal theta. A behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to four-fold increase in learning speed. This behavioral effect is accompanied by enhanced amplitude and synchrony of hippocampal local field potential (LFP)s, multi-unit excitation, and single-unit response patterns that depend on theta state. Additionally, training in the presence of hippocampal theta has led to increases in the salience of tone-induced unit firing patterns in the medial prefrontal cortex, followed by persistent multi-unit activity during the trace interval. In cerebellum, rhythmicity and precise synchrony of stimulus time-locked LFPs with those of hippocampus occur preferentially under the theta condition. Here we review these findings, integrate them into current models of hippocampal-dependent learning and suggest how improvement in our understanding of neurobiological oscillations is critical for theories of medial temporal lobe processes underlying intact and pathological learning. PMID:25918501

Harnessing the power of theta: natural manipulations of cognitive performance during hippocampal theta-contingent eyeblink conditioning.

Science.gov (United States)

Hoffmann, Loren C; Cicchese, Joseph J; Berry, Stephen D

2015-01-01

Neurobiological oscillations are regarded as essential to normal information processing, including coordination and timing of cells and assemblies within structures as well as in long feedback loops of distributed neural systems. The hippocampal theta rhythm is a 3-12 Hz oscillatory potential observed during cognitive processes ranging from spatial navigation to associative learning. The lower range, 3-7 Hz, can occur during immobility and depends upon the integrity of cholinergic forebrain systems. Several studies have shown that the amount of pre-training theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning. Our lab has used a brain-computer interface (BCI) that delivers eyeblink conditioning trials contingent upon the explicit presence or absence of hippocampal theta. A behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to four-fold increase in learning speed. This behavioral effect is accompanied by enhanced amplitude and synchrony of hippocampal local field potential (LFP)s, multi-unit excitation, and single-unit response patterns that depend on theta state. Additionally, training in the presence of hippocampal theta has led to increases in the salience of tone-induced unit firing patterns in the medial prefrontal cortex, followed by persistent multi-unit activity during the trace interval. In cerebellum, rhythmicity and precise synchrony of stimulus time-locked LFPs with those of hippocampus occur preferentially under the theta condition. Here we review these findings, integrate them into current models of hippocampal-dependent learning and suggest how improvement in our understanding of neurobiological oscillations is critical for theories of medial temporal lobe processes underlying intact and pathological learning.

Other characterizations of $\\beta$-$\\theta$-R0 topological spaces

OpenAIRE

Miguel Caldas Cueva

2013-01-01

In this paper we give other characterizations of $\\beta$-$\\theta$-$%R_0$ and also introduce a new separation axiom called$\\beta$-$\\theta$-$R_1$. It turns out that $\\beta$-$\\theta$-$R_1$ isstronger that $\\beta$-$\\theta$-$R_0$

Better than sleep: theta neurofeedback training accelerates memory consolidation.

Science.gov (United States)

Reiner, Miriam; Rozengurt, Roman; Barnea, Anat

2014-01-01

Consistent empirical results showed that both night and day sleep enhanced memory consolidation. In this study we explore processes of consolidation of memory during awake hours. Since theta oscillations have been shown to play a central role in exchange of information, we hypothesized that elevated theta during awake hours will enhance memory consolidation. We used a neurofeedback protocol, to enhance the relative power of theta or beta oscillations. Participants trained on a tapping task, were divided into three groups: neurofeedback theta; neurofeedback beta; control. We found a significant improvement in performance in the theta group, relative to the beta and control groups, immediately after neurofeedback. Performance was further improved after night sleep in all groups, with a significant advantage favoring the theta group. Theta power during training was correlated with the level of improvement, indicating a clear relationship between memory consolidation, and theta neurofeedback. Copyright © 2013 Elsevier B.V. All rights reserved.

73.7 Tb/s (96x3x256-Gb/s) mode-division-multiplexed DP-16QAM transmission with inline MM-EDFA

NARCIS (Netherlands)

Sleiffer, V.A.J.M.; Jung, Y.; Veljanovski, V.; Uden, van R.G.H.; Kuschnerov, M.; Kang, Q.; Grüner-Nielsen, L.; Sun, Y.; Richardson, D.J.; Alam, S.U.; Poletti, F.; Sahu, J.K.; Dhar, A.; Chen, H.; Inan, B.; Koonen, A.M.J.; Corbett, B.; Winfield, R.; Ellis, A.D.; Waardt, de H.

2012-01-01

We show transmission of a 73.7 Tb/s (96x3x256-Gb/s) DP-16QAM mode-division- multiplexed signal over 119km of few-mode fiber with inline multi-mode EDFA, using 6x6 MIMO digital signal processing. The total demonstrated net capacity is 57.6 Tb/s (SE 12 bits/s/Hz).

Lower trait frontal theta activity in mindfulness meditators

Directory of Open Access Journals (Sweden)

Guaraci Ken Tanaka

2014-09-01

Full Text Available Acute and long-term effects of mindfulness meditation on theta-band activity are not clear. The aim of this study was to investigate frontal theta differences between long- and short-term mindfulness practitioners before, during, and after mindfulness meditation. Twenty participants were recruited, of which 10 were experienced Buddhist meditators. Despite an acute increase in the theta activity during meditation in both the groups, the meditators showed lower trait frontal theta activity. Therefore, we suggested that this finding is a neural correlate of the expert practitioners’ ability to limit the processing of unnecessary information (e.g., discursive thought and increase the awareness of the essential content of the present experience. In conclusion, acute changes in the theta band throughout meditation did not appear to be a specific correlate of mindfulness but were rather related to the concentration properties of the meditation. Notwithstanding, lower frontal theta activity appeared to be a trait of mindfulness practices.

Quantum thetas on noncommutative T4 from embeddings into lattice

International Nuclear Information System (INIS)

Chang-Young, Ee; Kim, Hoil

2007-01-01

In this paper, we investigate the theta vector and quantum theta function over noncommutative T 4 from the embedding of RxZ 2 . Manin has constructed the quantum theta functions from the lattice embedding into vector space (x finite group). We extend Manin's construction of the quantum theta function to the embedding of vector space x lattice case. We find that the holomorphic theta vector exists only over the vector space part of the embedding, and over the lattice part we can only impose the condition for the Schwartz function. The quantum theta function built on this partial theta vector satisfies the requirement of the quantum theta function. However, two subsequent quantum translations from the embedding into the lattice part are nonadditive, contrary to the additivity of those from the vector space part

Task-dependent activity and connectivity predict episodic memory network-based responses to brain stimulation in healthy aging.

Science.gov (United States)

Vidal-Piñeiro, Dídac; Martin-Trias, Pablo; Arenaza-Urquijo, Eider M; Sala-Llonch, Roser; Clemente, Imma C; Mena-Sánchez, Isaias; Bargalló, Núria; Falcón, Carles; Pascual-Leone, Álvaro; Bartrés-Faz, David

2014-01-01

Transcranial magnetic stimulation (TMS) can affect episodic memory, one of the main cognitive hallmarks of aging, but the mechanisms of action remain unclear. To evaluate the behavioral and functional impact of excitatory TMS in a group of healthy elders. We applied a paradigm of repetitive TMS - intermittent theta-burst stimulation - over left inferior frontal gyrus in healthy elders (n = 24) and evaluated its impact on the performance of an episodic memory task with two levels of processing and the associated brain activity as captured by a pre and post fMRI scans. In the post-TMS fMRI we found TMS-related activity increases in left prefrontal and cerebellum-occipital areas specifically during deep encoding but not during shallow encoding or at rest. Furthermore, we found a task-dependent change in connectivity during the encoding task between cerebellum-occipital areas and the TMS-targeted left inferior frontal region. This connectivity change correlated with the TMS effects over brain networks. The results suggest that the aged brain responds to brain stimulation in a state-dependent manner as engaged by different tasks components and that TMS effect is related to inter-individual connectivity changes measures. These findings reveal fundamental insights into brain network dynamics in aging and the capacity to probe them with combined behavioral and stimulation approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

Directory of Open Access Journals (Sweden)

Sena Minjoli

2017-01-01

Full Text Available Transcranial magnetic stimulation (TMS and transcranial direct current stimulation (TDCS are two types of non-invasive transcranial brain stimulation (TBS. They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible. Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field “hot spots” in the cortex. However, these maxima were not substantially stronger than those seen in a healthy control. The electric field pattern induced by TMS was not substantially changed by the lesions. However, the average field strength generated by TDCS was substantially decreased. This effect occurred for both head models and even when both electrodes were distant to the lesion, caused by increased current shunting through the lesion and enlarged ventricles. Judging from the similar peak field strengths compared

Search for the exotic $\\Theta^+$ resonance in the NOMAD experiment

CERN Document Server

Samoylov, O; Autiero, D; Baldisseri, Alberto; Baldo-Ceolin, M; Banner, M; Bassompierre, G; Benslama, K; Besson, N; Bird, I; Blumenfeld, B; Bobisut, F; Bouchez, J; Boyd, S; Bueno, A; Bunyatov, S; Camilleri, L L; Cardini, A; Cattaneo, P W; Cavasinni, V; Cervera-Villanueva, A; Challis, R; Chukanov, A; Collazuol, G; Conforto, G; Conta, C; Contalbrigo, M; Cousins, R; Daniels, D; De Santo, A; Degaudenzi, H M; Del Prete, T; Di Lella, L; Dignan, T; Do Couto e Silva, E; Dumarchez, J; Ellis, M; Feldman, G J; Ferrari, R; Ferrère, D; Flaminio, V; Fraternali, M; Gaillard, J M; Gangler, E; Geiser, A; Geppert, D; Gibin, D; Gninenko, S; Godley, A; Gosset, J; Gouanère, M; Grant, A; Graziani, G; Guglielmi, A M; Gómez-Cadenas, J J; Gössling, C; Hagner, C; Hernando, J; Hubbard, D; Hurst, P; Hyett, N; Iacopini, E; Joseph, C; Juget, F; Kent, N; Kirsanov, M; Klimov, O; Kokkonen, J; Kovzelev, A; Krasnoperov, A V; La Rotonda, L; Lacaprara, S; Lachaud, C; Lakic, B; Lanza, A; Laveder, M; Letessier-Selvon, A A; Linssen, L; Ljubicic, A; Long, J; Lupi, A; Lyubushkin, V; Lévy, J M; Marchionni, A; Martelli, F; Mendiburu, J P; Meyer, J P; Mezzetto, M; Mishra, S R; Moorhead, G F; Méchain, X; Naumov, D; Nefedov, Yu; Nguyen-Mau, C; Nédélec, P; Orestano, D; Pastore, F; Peak, L S; Pennacchio, E; Pessard, H; Petti, R; Placci, A; Polesello, G; Pollmann, D; Polyarush, A Yu; Popov, B; Poulsen, C; Rebuffi, L; Rico, J; Riemann, P; Roda, C; Rubbia, André; Salvatore, F; Schahmaneche, K; Schmidt, B; Schmidt, T; Sconza, A; Sevior, M; Sillou, D; Soler, F J P; Sozzi, G; Steele, D; Stiegler, U; Stipcevic, M; Stolarczyk, T; Tareb-Reyes, M; Taylor, G N; Tereshchenko, V V; Toropin, A; Touchard, A M; Tovey, S N; Tran, M T; Tsesmelis, E; Ulrichs, J; Vacavant, L; Valdata-Nappi, M; Valuev, V; Vannucci, F; Varvell, K E; Veltri, M; Vercesi, V; Vidal-Sitjes, G; Vieira, J M; Vinogradova, T; Weber, F V; Weisse, T; Wilson, F F; Winton, L J; Yabsley, B D; Zaccone, Henri; Zuber, K; Zuccon, P

2007-01-01

A search for exotic Theta baryon via Theta -> proton +Ks decay mode in the NOMAD muon neutrino DIS data is reported. The special background generation procedure was developed. The proton identification criteria are tuned to maximize the sensitivity to the Theta signal as a function of xF which allows to study the Theta production mechanism. We do not observe any evidence for the Theta state in the NOMAD data. We provide an upper limit on Theta production rate at 90% CL as 2.13 per 1000 of neutrino interactions.

Kinetic description of linear theta-pinch equilibria

International Nuclear Information System (INIS)

Batchelor, D.B.; Davidson, R.C.

1975-01-01

Equilibrium properties of linear theta-pinch plasmas are studied within the framework of the steady-state (o/x=0) Vlasov-Maxwell equations. The analysis is carried out for an infinitely long plasma column aligned parallel to an externally applied axial magnetic field Bsub(z)sup(ext)esub(z). Equilibrium properties are calculated for the class of rigid-rotor Vlasov equilibria, in which the th component distribution function (Hsub(perpendicular), Psub(theta), upsilonsub(z) depends on perpendicular energy H and canonical angular momentum Psub(theta), exclusively through the linear combination Hsub(perpendicular)-ωsub(j)Psub(theta), where ω;=const.=angular velocity of mean rotation. General equilibrium relations that pertain to the entire class of rigid-rotor Vlasov equilibria are discussed; and specific examples of sharp- and diffuse-boundary equilibrium configurations are considered. Rigid-rotor density and magnetic field profiles are compared with experimentally observed profiles. A general prescription is given for determining the functional dependence of the equilibrium distribution function on Hsub(perpendicular)-ωsub(j)Psub(theta) in circumstances, where the density profile or magnetic field profile is specified. (author)

The theta-structure in string theories - 1: bosonic strings

International Nuclear Information System (INIS)

Li Miao.

1985-09-01

We explored the theta-structures in bosonic string theories which are similar to those in gauge field theories. The theta-structure of string is due to the multiply connected spatial compact subspace of space-time. The work of this paper shows that there is an energy band E(theta) in the string theory and one may move the tachyon out in theory by choosing some proper theta parameters. (author)

Quantum thetas on noncommutative Td with general embeddings

International Nuclear Information System (INIS)

Chang-Young, Ee; Kim, Hoil

2008-01-01

In this paper, we construct quantum theta functions over noncommutative T d with general embeddings. Manin has constructed quantum theta functions from the lattice embedding into vector space x finite group. We extend Manin's construction of quantum thetas to the case of general embedding of vector space x lattice x torus. It turns out that only for the vector space part of the embedding there exists the holomorphic theta vector, while for the lattice part there does not. Furthermore, the so-called quantum translations from embedding into the lattice part become non-additive, while those from the vector space part are additive

HCCR TBS steady state calculation by using GAMMA-FR and MELCOR

International Nuclear Information System (INIS)

Jin, Hyung Gon; Ahn, Mu-Young

2016-01-01

KAERI has participated in the development of HCCR (Helium Cooled Ceramic Reflector) TBS (Test Blanket System) as a member of the KO TBM Team. Conceptual design review of this system had been performed in 2015 and after resolving the chits, the final approval was achieved in March 2016. This safety issue is one of the category II chits in the CDR and resolution strategy was already approved, however, safety analysis should be done until PDR (Preliminary Design Review). In this paper, model and nodalization for the accident are given and preliminary result is included. Nominal design pressure of HCS loop is 8 MPa, therefore, as indicated in the figure below. During the break of cooling pipe between TBM and Shield, the high pressure coolant will ingress to the 'interspace' between TBM, Shield and Frame. The coolant will be released through the front gaps between TBM and Frame towards VV primary vacuum. Accident analysis about HCCR TBS LOCA and ICE into small confined volume has been done successfully. Inverspace volume is compatibly small volume for 8MPa helium loop rupture, which causes fast pressure build-up the space but it decrease within 10 seconds. It is expected that other type of TBM has almost the same behavior. Safety judgment to this temporary over press should be discussed with IO

Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

DEFF Research Database (Denmark)

Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo

2013-01-01

in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated c......TBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively......, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects...

Laboratory-induced learned helplessness attenuates approach motivation as indexed by posterior versus frontal theta activity.

Science.gov (United States)

Reznik, Samantha J; Nusslock, Robin; Pornpattananangkul, Narun; Abramson, Lyn Y; Coan, James A; Harmon-Jones, Eddie

2017-08-01

Research suggests that midline posterior versus frontal electroencephalographic (EEG) theta activity (PFTA) may reflect a novel neurophysiological index of approach motivation. Elevated PFTA has been associated with approach-related tendencies both at rest and during laboratory tasks designed to enhance approach motivation. PFTA is sensitive to changes in dopamine signaling within the fronto-striatal neural circuit, which is centrally involved in approach motivation, reward processing, and goal-directed behavior. To date, however, no studies have examined PFTA during a laboratory task designed to reduce approach motivation or goal-directed behavior. Considerable animal and human research supports the hypothesis put forth by the learned helplessness theory that exposure to uncontrollable aversive stimuli decreases approach motivation by inducing a state of perceived uncontrollability. Accordingly, the present study examined the effect of perceived uncontrollability (i.e., learned helplessness) on PFTA. EEG data were collected from 74 participants (mean age = 19.21 years; 40 females) exposed to either Controllable (n = 26) or Uncontrollable (n = 25) aversive noise bursts, or a No-Noise Condition (n = 23). In line with prediction, individuals exposed to uncontrollable aversive noise bursts displayed a significant decrease in PFTA, reflecting reduced approach motivation, relative to both individuals exposed to controllable noise bursts or the No-Noise Condition. There was no relationship between perceived uncontrollability and frontal EEG alpha asymmetry, another commonly used neurophysiological index of approach motivation. Results have implications for understanding the neurophysiology of approach motivation and establishing PFTA as a neurophysiological index of approach-related tendencies.

Macrophage colony stimulating factor (M-CSF) induces Fc receptor expression on macrophages

International Nuclear Information System (INIS)

Magee, D.M.; Wing, E.J.; Waheed, A.; Shadduck, R.K.

1986-01-01

M-CSF is a glycoprotein that stimulates bone marrow progenitor cells to proliferate and differentiate into macrophages (M theta). In addition, M-CSF can modulate the function of mature M theta. In this study, the authors determined the effect of M-CSF on expression of receptors for IgG (Fc receptors). Murine resident peritoneal M theta monolayers were incubated with either M-CSF, recombinant gamma interferon (IFN), or left untreated for 48 hrs. Expression of Fc receptors was assessed by microscopy using an antibody coated sheet erythrocytes (EA) rosette assay. The results indicated that M-CSF treated M theta had significantly higher numbers of bound EA (7.1 erythrocytes/M theta), than IFN M theta (4.4), or untreated M theta (2.5) (p 51 Cr labelled EA assay, CSF M theta (16,411 cpm), IFN M theta (10,887), untreated M theta (6897) (p < 0.001). Additionally, the maximal response was noted between 10 and 500 units M-CSF. Purified anti-M-CSF IgG, when included in the cultures, ablated the enhancement of EA binding, whereas normal rabbit IgG did not. These findings indicate that M-CSF is a potent inducer of Fc receptor expression on M theta and supports other data concerning the role of M-CSF as a biological response modifier

Contribution of the supplementary motor area and the cerebellum to the anticipatory postural adjustments and execution phases of human gait initiation.

Science.gov (United States)

Richard, Aliénor; Van Hamme, Angèle; Drevelle, Xavier; Golmard, Jean-Louis; Meunier, Sabine; Welter, Marie-Laure

2017-09-01

Several brain structures including the brainstem, the cerebellum and the frontal cortico-basal ganglia network, with the primary and premotor areas have been shown to participate in the functional organization of gait initiation and postural control in humans, but their respective roles remain poorly understood. The aim of this study was to better understand the role of the supplementary motor area (SMA) and posterior cerebellum in the gait initiation process. Gait initiation parameters were recorded in 22 controls both before and after continuous theta burst transcranial stimulation (cTBS) of the SMA and cerebellum, and were compared to sham stimulation, using a randomized double-blind design study. The two phases of gait initiation process were analyzed: anticipatory postural adjustments (APAs) and execution, with recordings of soleus and tibialis anterior muscles. Functional inhibition of the SMA led to a shortened APA phase duration with advanced and increased muscle activity; during execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Cerebellar functional inhibition did not influence the APA phase duration and amplitude but increased muscle co-activation, it decreased execution duration and showed a trend to increase velocity, with increased swing soleus muscle duration and activity. The results suggest that the SMA contributes to both the timing and amplitude of the APAs with no influence on step execution and the posterior cerebellum in the coupling between the APAs and execution phases and leg muscle activity pattern during gait initiation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Enhancement of multitasking performance and neural oscillations by transcranial alternating current stimulation

NARCIS (Netherlands)

Hsu, W.Y.; Zanto, T.P.; van Schouwenburg, M.R.; Gazzaley, A.

2017-01-01

Multitasking is associated with the generation of stimulus-locked theta (4–7 Hz) oscillations arising from prefrontal cortex (PFC). Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that influences endogenous brain oscillations. Here, we investigate

Ramanujan's theta functions

CERN Document Server

Cooper, Shaun

2017-01-01

Theta functions were studied extensively by Ramanujan. This book provides a systematic development of Ramanujan’s results and extends them to a general theory. The author’s treatment of the subject is comprehensive, providing a detailed study of theta functions and modular forms for levels up to 12. Aimed at advanced undergraduates, graduate students, and researchers, the organization, user-friendly presentation, and rich source of examples, lends this book to serve as a useful reference, a pedagogical tool, and a stimulus for further research. Topics, especially those discussed in the second half of the book, have been the subject of much recent research; many of which are appearing in book form for the first time. Further results are summarized in the numerous exercises at the end of each chapter.

Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

Science.gov (United States)

Zhu, G; Wang, Y; Li, J; Wang, J

2015-04-30

Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Leader neurons in population bursts of 2D living neural networks

International Nuclear Information System (INIS)

Eckmann, J-P; Zbinden, Cyrille; Jacobi, Shimshon; Moses, Elisha; Marom, Shimon

2008-01-01

Eytan and Marom (2006 J. Neurosci. 26 8465-76) recently showed that the spontaneous bursting activity of rat neuron cultures includes 'first-to-fire' cells that consistently fire earlier than others. Here, we analyze the behavior of these neurons in long-term recordings of spontaneous activity of rat hippocampal and rat cortical neuron cultures from three different laboratories. We identify precursor events that may either subside ('aborted bursts') or can lead to a full-blown burst ('pre-bursts'). We find that the activation in the pre-burst typically has a first neuron ('leader'), followed by a localized response in its neighborhood. Locality is diminished in the bursts themselves. The long-term dynamics of the leaders is relatively robust, evolving with a half-life of 23-34 h. Stimulation of the culture alters the leader distribution, but the distribution stabilizes within about 1 h. We show that the leaders carry information about the identity of the burst, as measured by the signature of the number of spikes per neuron in a burst. The number of spikes from leaders in the first few spikes of a precursor event is furthermore shown to be predictive with regard to the transition into a burst (pre-burst versus aborted burst). We conclude that the leaders play a role in the development of the bursts and conjecture that they are part of an underlying sub-network that is excited first and then acts as a nucleation center for the burst

Quantum Thetas on Noncommutative T^d with General Embeddings

OpenAIRE

Chang-Young, Ee; Kim, Hoil

2007-01-01

In this paper we construct quantum theta functions over noncommutative T^d with general embeddings. Manin has constructed quantum theta functions from the lattice embedding into vector space x finite group. We extend Manin's construction of quantum thetas to the case of general embedding of vector space x lattice x torus. It turns out that only for the vector space part of the embedding there exists the holomorphic theta vector, while for the lattice part there does not. Furthermore, the so-c...

Distinct slow and fast cortical theta dynamics in episodic memory retrieval.

Science.gov (United States)

Pastötter, Bernhard; Bäuml, Karl-Heinz T

2014-07-01

Brain oscillations in the theta frequency band (3-8 Hz) have been shown to be critically involved in human episodic memory retrieval. In prior work, both positive and negative relationships between cortical theta power and retrieval success have been reported. This study examined the hypothesis that slow and fast cortical theta oscillations at the edges of the traditional theta frequency band are differentially related to retrieval success. Scalp EEG was recorded in healthy human participants as they performed a cued-recall episodic memory task. Slow (~3 Hz) and fast (~7 Hz) theta oscillations at retrieval were examined as a function of whether an item was recalled or not and as a function of the items' output position at test. Recall success typically declines with output position, due to increases in interference level. The results showed that slow theta power was positively related but fast theta power was negatively related to retrieval success. Concurrent positive and negative episodic memory effects for slow and fast theta oscillations were dissociable in time and space, showing different time courses and different spatial locations on the scalp. Moreover, fast theta power increased from early to late output positions, whereas slow theta power was unaffected by items' output position. Together with prior work, the results suggest that slow and fast theta oscillations have distinct functional roles in episodic memory retrieval, with slow theta oscillations being related to processes of recollection and conscious awareness, and fast theta oscillations being linked to processes of interference and interference resolution. Copyright © 2014 Elsevier Inc. All rights reserved.

Staged theta pinch experiments

International Nuclear Information System (INIS)

Linford, R.K.; Downing, J.N.; Gribble, R.F.; Jacobson, A.R.; Platts, D.A.; Thomas, K.S.

1976-01-01

Two implosion heating circuits are being experimentally tested. The principal experiment in the program is the 4.5-m-long Staged Theta Pinch (STP). It uses two relatively low energy (50kJ and 100 kJ), high voltage (125 kV) capacitor banks to produce the theta pinch plasma inside the 20 cm i.d. quartz discharge tube. A lower voltage (50 kV), higher energy (750 kJ) capacitor bank is used to contain the plasma and provide a variable amount of adiabatic compression. Because the experiment produces a higher ratio of implosion heating to compressional heating than conventional theta pinches, it should be capable of producing high temperature plasmas with a much larger ratio of plasma radius to discharge tube radius than has been possible in the past. The Resonant Heating Experiment (RHX) in its initial configuration is the same as a 0.9-m-long section of the high voltage part of the STP experiment and all the plasma results here were obtained with the experiment in that configuration. Part of the implosion bank will be removed and a low inductance crowbar added to convert it to the resonant heating configuration. (U.K.)

Theta power is reduced in healthy cognitive aging.

Science.gov (United States)

Cummins, Tarrant D R; Finnigan, Simon

2007-10-01

The effects of healthy cognitive aging on electroencephalographic (EEG) theta (4.9-6.8 Hz) power were examined during performance of a modified Sternberg, S., 1966. High-speed scanning in human memory. Science 153, 652-654.) word recognition task. In a sample of fourteen young (mean age 21.9 years, range=18-27) and fourteen older (mean age 68.4 years, range=60-80) participants, theta power was found to be significantly lower in older adults during both the retention and recognition intervals. This theta power difference was greatest at the fronto-central midline electrode and occurred in parallel with a small, non-significant decrease in recognition accuracy in the older sample. A significant decrease in older adults' mean theta power was also observed in resting EEG, however, it was of substantially smaller magnitude than the task-related theta difference. It is proposed that a neurophysiological measure(s), such as task-specific frontal midline theta (fmtheta) power, may be a more sensitive marker of cognitive aging than task performance measures. Furthermore, as recent research indicates that fmtheta is generated primarily in the anterior cingulate cortex, the current findings support evidence that the function of brain networks incorporating this structure may be affected in cognitive aging.

Impaired theta-gamma coupling during working memory performance in schizophrenia.

Science.gov (United States)

Barr, Mera S; Rajji, Tarek K; Zomorrodi, Reza; Radhu, Natasha; George, Tony P; Blumberger, Daniel M; Daskalakis, Zafiris J

2017-11-01

Working memory deficits represent a core feature of schizophrenia. These deficits have been associated with dysfunctional dorsolateral prefrontal cortex (DLPFC) cortical oscillations. Theta-gamma coupling describes the modulation of gamma oscillations by theta phasic activity that has been directly associated with the ordering of information during working memory performance. Evaluating theta-gamma coupling may provide greater insight into the neural mechanisms mediating working memory deficits in this disorder. Thirty-eight patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls performed the verbal N-Back task administered at 4 levels, while EEG was recorded. Theta (4-7Hz)-gamma (30-50Hz) coupling was calculated for target and non-target correct trials for each working memory load. The relationship between theta-gamma coupling and accuracy was determined. Theta-gamma coupling was significantly and selectively impaired during correct responses to target letters among schizophrenia patients compared to healthy controls. A significant and positive relationship was found between theta-gamma coupling and 3-Back accuracy in controls, while this relationship was not observed in patients. These findings suggest that impaired theta-gamma coupling contribute to working memory dysfunction in schizophrenia. Future work is needed to evaluate the predictive utility of theta-gamma coupling as a neurophysiological marker for functional outcomes in this disorder. Copyright © 2017. Published by Elsevier B.V.

Enhanced {sup 18}F-FDG uptake in activated neutrophils is unaffected by respiratory burst inhibition with RGD

Energy Technology Data Exchange (ETDEWEB)

Paik, J. Y.; Lee, K. H.; Go, B. H.; Jeong, K. H.; Kim, H. K.; Choi, J. S.; Choi, Y.; Kim, P. T [Samsung Medical Center, Seoul (Korea, Republic of)

2004-07-01

Respiratory burst generation is an important response of activated neutrophils and is associated with enhanced glucose metabolism. Since such activation in dependent on adhesion through integrins, we investigated how integrin occupation with RGD influences respiratory burst response and {sup 18}F-FDG uptake in neutrophils. Human neutrophils separated from healthy volunteers were incubated in RPMI media. For RGD peptide inhibitory experiments, neutrophils were preincubated with 200 {mu} g/ml of cRGD peptides ad 37.deg. for 2 hr prior. Respiratory burst generation and uptake of {sup 18}F-FDG was then measured with or without PMA stimulation. Cellular total hexokinase levels were assayed with a colorimetric method. Treatment with RGD in the basal state resulted in a significant but relatively small increase in neutrophil superoxide release to 1.5{+-}0.25 fold o control levels (p<0.005). Whereas PMA stimulation caused a marked increase in superoxide generation, pretreatment with RGD caused a significant attenuation of this response to 35.6{+-}0.2% (p<0.005). PMA stimulation resulted in a significant increase in {sup 18}F-FDG uptake. However, unlike the attenution of superoxide generation, neutrophils pretreated with RGD before PMA stimulation showed an identical magnitude of enhanced {sup 18}F-FDG uptake (201.8{+-}20.5 of controls, p=0.0001). In addition, hexokinase levels were increased to comparable levels of approximately 1.5 fold for PMA stimulated neutrophils irrespective of RGD pretreatment. In conclusion, soluble RGD blocks stimulation of respiratory burst activation in neutrophils but does not inhibit stimulation of cellular glucose metabolism. This dissociation may contribute to maximally enhanced neutrophil FDG uptake in inflammatory lesions regardless of the occupancy of their integrin receptors.

Leptogenesis, $\\mu - \\tau$ Symmetry and $\\theta_{13}$

CERN Document Server

Mohapatra, Rabindra N; Yu, H; Yu, Haibo

2005-01-01

We show that in theories where neutrino masses arise from type I seesaw formula with three right handed neutrinos and where large atmospheric mixing angle owes its origin to an approximate leptonic $\\mu-\\tau$ interchange symmetry, the primordial lepton asymmetry of the Universe, $\\epsilon_l$ can be expressed in a simple form in terms of low energy neutrino oscillation parameters as $\\epsilon_l = (a \\Delta m^2_\\odot+ b \\Delta m^2_A \\theta^2_{13})$, where $a$ and $b$ are parameters characterizing high scale physics and are each of order $\\leq 10^{-2} $ eV$^{-2}$. We also find that for the case of two right handed neutrinos, $\\epsilon_l \\propto \\theta^2_{13}$ as a result of which, the observed value of baryon to photon ratio implies a lower limit on $\\theta_{13}$. For specific choices of the CP phase $\\delta$ we find $\\theta_{13}$ is predicted to be between $0.10-0.15$.

Expected reward modulates encoding-related theta activity before an event.

Science.gov (United States)

Gruber, Matthias J; Watrous, Andrew J; Ekstrom, Arne D; Ranganath, Charan; Otten, Leun J

2013-01-01

Oscillatory brain activity in the theta frequency range (4-8 Hz) before the onset of an event has been shown to affect the likelihood of successfully encoding the event into memory. Recent work has also indicated that frontal theta activity might be modulated by reward, but it is not clear how reward expectancy, anticipatory theta activity, and memory formation might be related. Here, we used scalp electroencephalography (EEG) to assess the relationship between these factors. EEG was recorded from healthy adults while they memorized a series of words. Each word was preceded by a cue that indicated whether a high or low monetary reward would be earned if the word was successfully remembered in a later recognition test. Frontal theta power between the presentation of the reward cue and the onset of a word was predictive of later memory for the word, but only in the high reward condition. No theta differences were observed before word onset following low reward cues. The magnitude of prestimulus encoding-related theta activity in the high reward condition was correlated with the number of high reward words that were later confidently recognized. These findings provide strong evidence for a link between reward expectancy, theta activity, and memory encoding. Theta activity before event onset seems to be especially important for the encoding of motivationally significant stimuli. One possibility is that dopaminergic activity during reward anticipation mediates frontal theta activity related to memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Theta function identities associated with Ramanujan's modular ...

Indian Academy of Sciences (India)

In Chapter 20 of his second notebook [6], Ramanujan recorded several theta function identities associated with modular equations of composite degree 15. These identities have previously been proved by Berndt in [3]. But he proved most of these theta function identities using modular equations. These identities can also ...

The Codacs™ direct acoustic cochlear implant actuator: exploring alternative stimulation sites and their stimulation efficiency.

Science.gov (United States)

Grossöhmichen, Martin; Salcher, Rolf; Kreipe, Hans-Heinrich; Lenarz, Thomas; Maier, Hannes

2015-01-01

This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia) in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW). Here the perilymph stimulation with a K-piston through a stapes footplate (SFP) fenestration (N = 10) as well as stimulation of the stapes head (SH) with a Bell prosthesis (N = 9), SFP stimulation with an Omega/Aerial prosthesis (N = 8) and reverse RW stimulation (N = 10) were performed in cadaveric human temporal bones (TBs). Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL) using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5-141.8 eq. dB SPL; Omega/Aerial: 123.6-143.9 eq. dB SPL), being significantly more efficient than K-piston perilymph stimulation (108.6-131.6 eq. dB SPL) and RW stimulation (108.3-128.2 eq. dB SPL). Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented.

Lee weight enumerators of self-dual codes and theta functions

NARCIS (Netherlands)

Asch, van A.G.; Martens, F.J.L.

2008-01-01

The theory of modular forms, in particular theta functions, and coding theory are in a remarkable way connected. The connection is established by defining a suitable lattice corresponding to the given code, and considering its theta function. First we define some special theta functions, and

The third-stimulus temporal discrimination threshold: focusing on the temporal processing of sensory input within primary somatosensory cortex.

Science.gov (United States)

Leodori, Giorgio; Formica, Alessandra; Zhu, Xiaoying; Conte, Antonella; Belvisi, Daniele; Cruccu, Giorgio; Hallett, Mark; Berardelli, Alfredo

2017-10-01

The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information, but little is known about the physiological correlates of somatosensory temporal discrimination. The objective of this study was to investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the third-stimulus temporal discrimination threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus following a pair of stimuli delivered at the STDT. The STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1 continuous theta-burst stimulation (S1-cTBS) on the STDT and ThirdDT. Results show that ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, although the latter was affected to a greater extent and for a longer period of time. We conclude that the interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1, probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination. NEW & NOTEWORTHY To investigate whether the time interval required to discriminate between stimuli varies according to changes in the stimulation pattern, we used the third-stimulus temporal discrimination threshold (ThirdDT). We found that the somatosensory temporal discrimination acuity varies according to the number of stimuli in the

Medial septal GABAergic projection neurons promote object exploration behavior and type 2 theta rhythm

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Gangadharan, Gireesh; Shin, Jonghan; Kim, Seong-Wook; Kim, Angela; Paydar, Afshin; Kim, Duk-Soo; Miyazaki, Taisuke; Watanabe, Masahiko; Yanagawa, Yuchio; Kim, Jinhyun; Kim, Yeon-Soo; Kim, Daesoo; Shin, Hee-Sup

2016-01-01

Exploratory drive is one of the most fundamental emotions, of all organisms, that are evoked by novelty stimulation. Exploratory behavior plays a fundamental role in motivation, learning, and well-being of organisms. Diverse exploratory behaviors have been described, although their heterogeneity is not certain because of the lack of solid experimental evidence for their distinction. Here we present results demonstrating that different neural mechanisms underlie different exploratory behaviors. Localized Cav3.1 knockdown in the medial septum (MS) selectively enhanced object exploration, whereas the null mutant (KO) mice showed enhanced-object exploration as well as open-field exploration. In MS knockdown mice, only type 2 hippocampal theta rhythm was enhanced, whereas both type 1 and type 2 theta rhythm were enhanced in KO mice. This selective effect was accompanied by markedly increased excitability of septo-hippocampal GABAergic projection neurons in the MS lacking T-type Ca2+ channels. Furthermore, optogenetic activation of the septo-hippocampal GABAergic pathway in WT mice also selectively enhanced object exploration behavior and type 2 theta rhythm, whereas inhibition of the same pathway decreased the behavior and the rhythm. These findings define object exploration distinguished from open-field exploration and reveal a critical role of T-type Ca2+ channels in the medial septal GABAergic projection neurons in this behavior. PMID:27208094

Transcranial alternating current stimulation (tACS increases risk taking behavior in the Balloon Analogue Risk Task

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Tal eSela

2012-02-01

Full Text Available The process of evaluating risks and benefits involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC. It has been proposed that in conflict and reward situations, theta-band (4–8 Hz oscillatory activity in the frontal cortex may reflect an electrophysiological mechanism for coordinating neural networks monitoring behavior, as well as facilitating task-specific adaptive changes. The goal of the present study was to investigate the hypothesis that theta-band oscillatory balance between right and left frontal and prefrontal regions, with a predominance role to the right hemisphere, is crucial for regulatory control during decision-making under risk. In order to explore this hypothesis, we used transcranial Alternating Current Stimulation (tACS, a novel technique that provides the opportunity to explore the functional role of neuronal oscillatory activities and to establish a causal link between specific oscillations and functional lateralization in risky decision-making situations. For this aim, healthy participants were randomly allocated to one of three stimulation groups (LH stimulation / RH stimulation / Sham stimulation, with active AC stimulation delivered in a frequency-dependent manner (at 6.5 Hz; 1mA peak to-peak. During the AC stimulation, participants performed the Balloon Analog Risk Task. This experiment revealed that participants receiving LH stimulation displayed riskier decision-making style compared to sham and RH stimulation groups. However, there was no difference in decision-making behaviors between sham and RH stimulation groups. The current study extends the notion that DLPFC activity is critical for adaptive decision-making in the context of risk-taking and emphasis the role of theta-band oscillatory activity during risky decision-making situations.

Neural dynamics during repetitive visual stimulation

Science.gov (United States)

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

Hippocampal theta activity in the acute cerveau isolé cat.

Science.gov (United States)

Gottesmann, C; Zernicki, B; Gandolfo, G

1981-01-01

In three cerveau isole cats, cortical and hippocampal EEG activity were recorded. In the cortical records, spindles alternated with low-voltage activity, whereas theta activity dominated in the hippocampus. The amount and frequency of theta were similar to those described previously for the pretrigeminal cat. In confirmation of previous results on rats, although cortical EEG activity differs in cerveau isole cat and pretrigeminal cat, both preparations show domination of theta activity in the hippocampus. It is concluded that the mesencephalic transection eliminates inhibitory effects from the lower brainstem on generators of the theta rhythm.

Beta burst dynamics in Parkinson's disease OFF and ON dopaminergic medication.

Science.gov (United States)

Tinkhauser, Gerd; Pogosyan, Alek; Tan, Huiling; Herz, Damian M; Kühn, Andrea A; Brown, Peter

2017-11-01

Exaggerated basal ganglia beta activity (13-35 Hz) is commonly found in patients with Parkinson's disease and can be suppressed by dopaminergic medication, with the degree of suppression being correlated with the improvement in motor symptoms. Importantly, beta activity is not continuously elevated, but fluctuates to give beta bursts. The percentage number of longer beta bursts in a given interval is positively correlated with clinical impairment in Parkinson's disease patients. Here we determine whether the characteristics of beta bursts are dependent on dopaminergic state. Local field potentials were recorded from the subthalamic nucleus of eight Parkinson's disease patients during temporary lead externalization during surgery for deep brain stimulation. The recordings took place with the patient quietly seated following overnight withdrawal of levodopa and after administration of levodopa. Beta bursts were defined by applying a common amplitude threshold and burst characteristics were compared between the two drug conditions. The amplitude of beta bursts, indicative of the degree of local neural synchronization, progressively increased with burst duration. Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts. Synchronization, however, was not limited to local neural populations during bursts, but also, when such bursts were cotemporaneous across the hemispheres, was evidenced by bilateral phase synchronization. The probability of beta bursts and the proportion of cotemporaneous bursts were reduced by levodopa. The percentage number of longer beta bursts in a given interval was positively related to motor impairment, while the opposite was true for the percentage number of short duration beta bursts. Importantly, the decrease in burst duration was also correlated with the motor improvement. In conclusion, we demonstrate that long duration beta bursts are associated with an increase in local and

Dual Stimulus-Dependent Effect of Oenothera paradoxa Extract on the Respiratory Burst in Human Leukocytes: Suppressing for Escherichia coli and Phorbol Myristate Acetate and Stimulating for Formyl-Methionyl-Leucyl-Phenylalanine

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Izabela Burzynska-Pedziwiatr

2014-01-01

Full Text Available Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA, and formyl-methionyl-leucyl-phenylalanine (fMLP. Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05 and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05. Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D-glucose (PGG, the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.

Dual stimulus-dependent effect of Oenothera paradoxa extract on the respiratory burst in human leukocytes: suppressing for Escherichia coli and phorbol myristate acetate and stimulating for formyl-methionyl-leucyl-phenylalanine.

Science.gov (United States)

Burzynska-Pedziwiatr, Izabela; Bukowiecka-Matusiak, Malgorzata; Wojcik, Marzena; Machala, Waldemar; Bienkiewicz, Malgorzata; Spolnik, Grzegorz; Danikiewicz, Witold; Wozniak, Lucyna Alicja

2014-01-01

Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.

Laser--plasma interaction in a theta-pinch geometry

International Nuclear Information System (INIS)

Armstrong, W.T.

1978-06-01

Prompt stimulated Brillouin scatter (SBS) is studied in an experiment wherein a high power, pulsed CO 2 laser irradiates an independently produced, theta-pinch plasma. SBS does not significantly affect laser heating of the plasma. Measurements of density profiles and temperature histories permitted examination of laser refraction, local heating and net absorption. Refractive containment of the CO 2 laser beam by an on-axis density minimum was observed at early times during the laser pulse. However, refractive containment was lost at late times due to the diffusive loss of the density minimum. Classical modeling of the expected heating required ''bleached'' absorption to account for the observed heating. A plasma absorptivity of approximately 46% was inferred from calorimetry measurements at 250 mtorr fill pressure. These results confirm that classical heating and refraction dominated the laser-plasma interaction

Theta dynamics in rat: speed and acceleration across the Septotemporal axis.

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Lauren L Long

Full Text Available Theta (6-12 Hz rhythmicity in the local field potential (LFP reflects a clocking mechanism that brings physically isolated neurons together in time, allowing for the integration and segregation of distributed cell assemblies. Variation in the theta signal has been linked to locomotor speed, sensorimotor integration as well as cognitive processing. Previously, we have characterized the relationship between locomotor speed and theta power and how that relationship varies across the septotemporal (long axis of the hippocampus (HPC. The current study investigated the relationship between whole body acceleration, deceleration and theta indices at CA1 and dentate gyrus (DG sites along the septotemporal axis of the HPC in rats. Results indicate that whole body acceleration and deceleration predicts a significant amount of variability in the theta signal beyond variation in locomotor speed. Furthermore, deceleration was more predictive of variation in theta amplitude as compared to acceleration as rats traversed a linear track. Such findings highlight key variables that systematically predict the variability in the theta signal across the long axis of the HPC. A better understanding of the relative contribution of these quantifiable variables and their variation as a function of experience and environmental conditions should facilitate our understanding of the relationship between theta and sensorimotor/cognitive functions.

A pedagogical introduction to theta functions

International Nuclear Information System (INIS)

Koh, I.G.; Shin, H.J.

1988-01-01

This paper reports on revolutions in physics that have been frequently accompanied by new developments in mathematics. In seventeenth century, Newton has initiated a program of describing celestial motion by classical mechanics. Integral and differential calculus was essential tool. Orbits of the moon and the earth are given by solving the differential equation of Newton's equation. Imagine a situation where one tries to solve such orbits without integral and differential calculus. Similar revolutions in understanding quantum gravity and in making deep connections between statistical and string physics are under progresses. One of indispensible tools are the theory of theta functions on Riemann surfaces. Since the literature of theta functions is mainly written by professional mathematician, physicists feel somewhat uneasy to begin to read a long chapters of lemmas and theorems, but it is now generally accepted that theta function is essential in understanding two-dimensional conformal field theory as the integral and differential calculus was indispensible in Newtonian mechanics

Influence of laboratory degradation methods and bonding application parameters on microTBS of self-etch adhesives to dentin.

Science.gov (United States)

Erhardt, Maria Carolina G; Pisani-Proença, Jatyr; Osorio, Estrella; Aguilera, Fátima S; Toledano, Manuel; Osorio, Raquel

2011-04-01

To evaluate the laboratory resistance to degradation and the use of different bonding treatments on resin-dentin bonds formed with three self-etching adhesive systems. Flat, mid-coronal dentin surfaces from extracted human molars were bonded according to manufacturer's directions and submitted to two challenging regimens: (A) chemical degradation with 10% NaOC1 immersion for 5 hours; and (B) fatigue loading at 90 N using 50,000 cycles at 3.0 Hz. Additional dentin surfaces were bonded following four different bonding application protocols: (1) according to manufacturer's directions; (2) acid-etched with 36% phosphoric acid (H3PO4) for 15 seconds; (3) 10% sodium hypochlorite (NaOClaq) treated for 2 minutes, after H3PO4-etching; and (4) doubling the application time of the adhesives. Two one-step self-etch adhesives (an acetone-based: Futurabond/FUT and an ethanol-based: Futurabond NR/FNR) and a two-step self-etch primer system (Clearfil SE Bond/CSE) were examined. Specimens were sectioned into beams and tested for microtensile bond strength (microTBS). Selected debonded specimens were observed under scanning electron microscopy (SEM). Data (MPa) were analyzed by ANOVA and multiple comparisons tests (alpha= 0.05). microTBS significantly decreased after chemical and mechanical challenges (Padhesive systems, regardless the bonding protocol. FUT attained the highest microTBS after doubling the application time. H3PO4 and H3PO4 + NaOCl pretreatments significantly decreased bonding efficacy of the adhesives.

The Codacs™ direct acoustic cochlear implant actuator: exploring alternative stimulation sites and their stimulation efficiency.

Directory of Open Access Journals (Sweden)

Martin Grossöhmichen

Full Text Available This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW. Here the perilymph stimulation with a K-piston through a stapes footplate (SFP fenestration (N = 10 as well as stimulation of the stapes head (SH with a Bell prosthesis (N = 9, SFP stimulation with an Omega/Aerial prosthesis (N = 8 and reverse RW stimulation (N = 10 were performed in cadaveric human temporal bones (TBs. Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5-141.8 eq. dB SPL; Omega/Aerial: 123.6-143.9 eq. dB SPL, being significantly more efficient than K-piston perilymph stimulation (108.6-131.6 eq. dB SPL and RW stimulation (108.3-128.2 eq. dB SPL. Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented.

POPULATION III GAMMA-RAY BURSTS AND BREAKOUT CRITERIA FOR ACCRETION-POWERED JETS

Energy Technology Data Exchange (ETDEWEB)

Nagakura, Hiroki; Suwa, Yudai [Yukawa Institute for Theoretical Physics, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan); Ioka, Kunihito, E-mail: hiroki@heap.phys.waseda.ac.jp [KEK Theory Center, 1-1 Oho, Tsukuba 305-0801 (Japan)

2012-08-01

We investigate the propagation of accretion-powered jets in various types of massive stars such as Wolf-Rayet stars, light Population III (Pop III) stars, and massive Pop III stars, all of which are the progenitor candidates of gamma-ray bursts (GRBs). We perform two-dimensional axisymmetric simulations of relativistic hydrodynamics, taking into account both the envelope collapse and the jet propagation (i.e., the negative feedback of the jet on the accretion). Based on our hydrodynamic simulations, we show for the first time that the accretion-powered jet can potentially break out relativistically from the outer layers of Pop III progenitors. In our simulations, the accretion rate is estimated by the mass flux going through the inner boundary, and the jet is injected with a fixed accretion-to-jet conversion efficiency {eta}. By varying the efficiency {eta} and opening angle {theta}{sub op} for more than 40 models, we find that the jet can make a relativistic breakout from all types of progenitors for GRBs if a simple condition {eta} {approx}> 10{sup -4}({theta}{sub op}/8 Degree-Sign ){sup 2} is satisfied, which is consistent with analytical estimates. Otherwise no explosion or some failed spherical explosions occur.

Atmospheric, long baseline, and reactor neutrino data constraints on theta_{13}.

Science.gov (United States)

Roa, J E; Latimer, D C; Ernst, D J

2009-08-07

An atmospheric neutrino oscillation tool that uses full three-neutrino oscillation probabilities and a full three-neutrino treatment of the Mikheyev-Smirnov-Wolfenstein effect, together with an analysis of the K2K, MINOS, and CHOOZ data, is used to examine the bounds on theta_{13}. The recent, more finely binned, Super-K atmospheric data are employed. For L/E_{nu} greater, similar 10;{4} km/GeV, we previously found significant linear in theta_{13} terms. This analysis finds theta_{13} bounded from above by the atmospheric data while bounded from below by CHOOZ. The origin of this result arises from data in the previously mentioned very long baseline region; here, matter effects conspire with terms linear in theta_{13} to produce asymmetric bounds on theta_{13}. Assuming CP conservation, we find theta_{13} = -0.07_{-0.11};{+0.18} (90% C.L.).

Movement-related theta rhythm in humans: coordinating self-directed hippocampal learning.

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Raphael Kaplan

Full Text Available The hippocampus is crucial for episodic or declarative memory and the theta rhythm has been implicated in mnemonic processing, but the functional contribution of theta to memory remains the subject of intense speculation. Recent evidence suggests that the hippocampus might function as a network hub for volitional learning. In contrast to human experiments, electrophysiological recordings in the hippocampus of behaving rodents are dominated by theta oscillations reflecting volitional movement, which has been linked to spatial exploration and encoding. This literature makes the surprising cross-species prediction that the human hippocampal theta rhythm supports memory by coordinating exploratory movements in the service of self-directed learning. We examined the links between theta, spatial exploration, and memory encoding by designing an interactive human spatial navigation paradigm combined with multimodal neuroimaging. We used both non-invasive whole-head Magnetoencephalography (MEG to look at theta oscillations and Functional Magnetic Resonance Imaging (fMRI to look at brain regions associated with volitional movement and learning. We found that theta power increases during the self-initiation of virtual movement, additionally correlating with subsequent memory performance and environmental familiarity. Performance-related hippocampal theta increases were observed during a static pre-navigation retrieval phase, where planning for subsequent navigation occurred. Furthermore, periods of the task showing movement-related theta increases showed decreased fMRI activity in the parahippocampus and increased activity in the hippocampus and other brain regions that strikingly overlap with the previously observed volitional learning network (the reverse pattern was seen for stationary periods. These fMRI changes also correlated with participant's performance. Our findings suggest that the human hippocampal theta rhythm supports memory by coordinating

Priming stimulation of basal but not lateral amygdala affects long-term potentiation in the rat dentate gyrus in vivo.

Science.gov (United States)

Li, Z; Richter-Levin, G

2013-08-29

The amygdaloid complex, or amygdala, has been implicated in assigning emotional significance to sensory information and producing appropriate behavioral responses to external stimuli. The lateral and basal nuclei (lateral and basal amygdala), which are termed together as basolateral amygdala, play a critical role in emotional and motivational learning and memory. It has been established that the basolateral amygdala activation by behavioral manipulations or direct electrical stimulation can modulate hippocampal long-term potentiation (LTP), a putative cellular mechanism of memory. However, the specific functional role of each subnucleus in the modulation of hippocampal LTP has not been studied yet, even though studies have shown cytoarchitectural differences between the basal and lateral amygdala and differences in the connections of each one of them to other brain areas. In this study we have tested the effects of lateral or basal amygdala pre-stimulation on hippocampal dentate gyrus LTP, induced by theta burst stimulation of the perforant path, in anesthetized rats. We found that while priming stimulation of the lateral amygdala did not affect LTP of the dentate gyrus, priming stimulation of the basal amygdala enhanced the LTP response when the priming stimulation was relatively weak, but impaired it when it was relatively strong. These results show that the basal and lateral nuclei of the amygdala, which have been already shown to differ in their anatomy and connectivity, may also have different functional roles. These findings raise the possibility that the lateral and basal amygdala differentially modulate memory processes in the hippocampus under emotional and motivational situations. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Enhancing early consolidation of human episodic memory by theta EEG neurofeedback.

Science.gov (United States)

Rozengurt, Roman; Shtoots, Limor; Sheriff, Aviv; Sadka, Ofir; Levy, Daniel A

2017-11-01

Consolidation of newly formed memories is readily disrupted, but can it be enhanced? Given the prominent role of hippocampal theta oscillations in memory formation and retrieval, we hypothesized that upregulating theta power during early stages of consolidation might benefit memory stability and persistence. We used EEG neurofeedback to enable participants to selectively increase theta power in their EEG spectra following episodic memory encoding, while other participants engaged in low beta-focused neurofeedback or passively viewed a neutral nature movie. Free recall assessments immediately following the interventions, 24h later and 7d later all indicated benefit to memory of theta neurofeedback, relative to low beta neurofeedback or passive movie-viewing control conditions. The degree of benefit to memory was correlated with the extent of theta power modulation, but not with other spectral changes. Theta enhancement may provide optimal conditions for stabilization of new hippocampus-dependent memories. Copyright © 2017 Elsevier Inc. All rights reserved.

Engineering prototypes for theta-pinch devices

International Nuclear Information System (INIS)

Hansborough, L.D.; Hammer, C.F.; Hanks, K.W.; McDonald, T.E.; Nunnally, W.C.

1975-01-01

Past, present, and future engineering prototypes for theta-pinch plasma-physics devices at Los Alamos Scientific Laboratory are discussed. Engineering prototypes are designed to test and evaluate all components under system conditions expected on actual plasma-physics experimental devices. The importance of engineering prototype development increases as the size and complexity of the plasma-physics device increases. Past experiences with the Scyllac prototype and the Staged Theta-Pinch prototype are discussed and evaluated. The design of the proposed Staged Scyllac prototype and the Large Staged Scyllac implosion prototype assembly are discussed

Gender difference in the theta/alpha ratio during the induction of peaceful audiovisual modalities.

Science.gov (United States)

Yang, Chia-Yen; Lin, Ching-Po

2015-09-01

Gender differences in emotional perception have been found in numerous psychological and psychophysiological studies. The conducting modalities in diverse characteristics of different sensory systems make it interesting to determine how cooperation and competition contribute to emotional experiences. We have previously estimated the bias from the match attributes of auditory and visual modalities and revealed specific brain activity frequency patterns related to a peaceful mood. In that multimodality experiment, we focused on how inner-quiet information is processed in the human brain, and found evidence of auditory domination from the theta-band activity. However, a simple quantitative description of these three frequency bands is lacking, and no studies have assessed the effects of peacefulness on the emotional state. Therefore, the aim of this study was to use magnetoencephalography to determine if gender differences exist (and when and where) in the frequency interactions underpinning the perception of peacefulness. This study provides evidence of auditory and visual domination in perceptual bias during multimodality processing of peaceful consciousness. The results of power ratio analyses suggest that the values of the theta/alpha ratio are associated with a modality as well as hemispheric asymmetries in the anterior-to-posterior direction, which shift from right to left with the auditory to visual stimulations in a peaceful mood. This means that the theta/alpha ratio might be useful for evaluating emotion. Moreover, the difference was found to be most pronounced for auditory domination and visual sensitivity in the female group.

Neutron stars as X-ray burst sources. II. Burst energy histograms and why they burst

International Nuclear Information System (INIS)

Baan, W.A.

1979-01-01

In this work we explore some of the implications of a model for X-ray burst sources where bursts are caused by Kruskal-Schwarzschild instabilities at the magnetopause of an accreting and rotating neutron star. A number of simplifying assumptions are made in order to test the model using observed burst-energy histograms for the rapid burster MXB 1730--335. The predicted histograms have a correct general shape, but it appears that other effects are important as well, and that mode competition, for instance, may suppress the histograms at high burst energies. An explanation is ventured for the enhancement in the histogram at the highest burst energies, which produces the bimodal shape in high accretion rate histograms. Quantitative criteria are given for deciding when accreting neutron stars are steady sources or burst sources, and these criteria are tested using the X-ray pulsars

Theta variation and spatiotemporal scaling along the septotemporal axis of the hippocampus

Directory of Open Access Journals (Sweden)

Lauren L Long

2015-03-01

Full Text Available Hippocampal theta has been related to locomotor speed, attention, anxiety, sensorimotor integration and memory among other emergent phenomena. One difficulty in understanding the function of theta is that the hippocampus (HPC modulates voluntary behavior at the same time that it processes sensory input. Both functions are correlated with characteristic changes in theta indices. The current review highlights a series of studies examining theta local field potential (LFP signals across the septotemporal or longitudinal axis of the HPC. While the theta signal is coherent throughout the entirety of the HPC, the amplitude, but not the frequency, of theta varies significantly across its three-dimensional expanse. We suggest that the theta signal offers a rich vein of information about how distributed neuronal ensembles support emergent function. Further, we speculate that emergent function across the long axis varies with respect to spatiotemporal scale. Thus, septal hippocampus processes details of the proximal spatiotemporal environment while more temporal aspects process larger spaces and wider time-scales. The degree to which emergent functions are supported by the synchronization of theta across the septotemporal axis is an open question. Our working model is that theta synchrony serves to bind ensembles representing varying resolutions of spatiotemporal information at interdependent septotemporal areas of the HPC. Such synchrony and cooperative interactions along the septotemporal axis likely support memory formation and subsequent consolidation and retrieval.

Visual cortex responses reflect temporal structure of continuous quasi-rhythmic sensory stimulation.

Science.gov (United States)

Keitel, Christian; Thut, Gregor; Gross, Joachim

2017-02-01

Neural processing of dynamic continuous visual input, and cognitive influences thereon, are frequently studied in paradigms employing strictly rhythmic stimulation. However, the temporal structure of natural stimuli is hardly ever fully rhythmic but possesses certain spectral bandwidths (e.g. lip movements in speech, gestures). Examining periodic brain responses elicited by strictly rhythmic stimulation might thus represent ideal, yet isolated cases. Here, we tested how the visual system reflects quasi-rhythmic stimulation with frequencies continuously varying within ranges of classical theta (4-7Hz), alpha (8-13Hz) and beta bands (14-20Hz) using EEG. Our findings substantiate a systematic and sustained neural phase-locking to stimulation in all three frequency ranges. Further, we found that allocation of spatial attention enhances EEG-stimulus locking to theta- and alpha-band stimulation. Our results bridge recent findings regarding phase locking ("entrainment") to quasi-rhythmic visual input and "frequency-tagging" experiments employing strictly rhythmic stimulation. We propose that sustained EEG-stimulus locking can be considered as a continuous neural signature of processing dynamic sensory input in early visual cortices. Accordingly, EEG-stimulus locking serves to trace the temporal evolution of rhythmic as well as quasi-rhythmic visual input and is subject to attentional bias. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Burst-induced anti-Hebbian depression acts through short-term synaptic dynamics to cancel redundant sensory signals.

Science.gov (United States)

Harvey-Girard, Erik; Lewis, John; Maler, Leonard

2010-04-28

Weakly electric fish can enhance the detection and localization of important signals such as those of prey in part by cancellation of redundant spatially diffuse electric signals due to, e.g., their tail bending. The cancellation mechanism is based on descending input, conveyed by parallel fibers emanating from cerebellar granule cells, that produces a negative image of the global low-frequency signals in pyramidal cells within the first-order electrosensory region, the electrosensory lateral line lobe (ELL). Here we demonstrate that the parallel fiber synaptic input to ELL pyramidal cell undergoes long-term depression (LTD) whenever both parallel fiber afferents and their target cells are stimulated to produce paired burst discharges. Paired large bursts (4-4) induce robust LTD over pre-post delays of up to +/-50 ms, whereas smaller bursts (2-2) induce weaker LTD. Single spikes (either presynaptic or postsynaptic) paired with bursts did not induce LTD. Tetanic presynaptic stimulation was also ineffective in inducing LTD. Thus, we have demonstrated a form of anti-Hebbian LTD that depends on the temporal correlation of burst discharge. We then demonstrated that the burst-induced LTD is postsynaptic and requires the NR2B subunit of the NMDA receptor, elevation of postsynaptic Ca(2+), and activation of CaMKIIbeta. A model incorporating local inhibitory circuitry and previously identified short-term presynaptic potentiation of the parallel fiber synapses further suggests that the combination of burst-induced LTD, presynaptic potentiation, and local inhibition may be sufficient to explain the generation of the negative image and cancellation of redundant sensory input by ELL pyramidal cells.

Independent delta/theta rhythms in the human hippocampus and entorhinal cortex

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Florian Mormann

2008-05-01

Full Text Available Theta oscillations in the medial temporal lobe (MTL of mammals are involved in various functions such as spatial navigation, sensorimotor integration, and cognitive processing. While the theta rhythm was originally assumed to originate in the medial septum, more recent studies suggest autonomous theta generation in the MTL. Although coherence between entorhinal and hippocampal theta activity has been found to influence memory formation, it remains unclear whether these two structures can generate theta independently. In this study we analyzed intracranial electroencephalographic (EEG recordings from 22 patients with unilateral hippocampal sclerosis undergoing presurgical evaluation prior to resection of the epileptic focus. Using a wavelet-based, frequency-band-specific measure of phase synchronization, we quantified synchrony between 10 different recording sites along the longitudinal axis of the hippocampal formation in the non-epileptic brain hemisphere. We compared EEG synchrony between adjacent recording sites (i within the entorhinal cortex, (ii within the hippocampus, and (iii between the hippocampus and entorhinal cortex. We observed a significant interregional gap in synchrony for the delta and theta band, indicating the existence of independent delta/theta rhythms in different subregions of the human MTL. The interaction of these rhythms could represent the temporal basis for the information processing required for mnemonic encoding and retrieval.

A computational study on altered theta-gamma coupling during learning and phase coding.

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Xuejuan Zhang

Full Text Available There is considerable interest in the role of coupling between theta and gamma oscillations in the brain in the context of learning and memory. Here we have used a neural network model which is capable of producing coupling of theta phase to gamma amplitude firstly to explore its ability to reproduce reported learning changes and secondly to memory-span and phase coding effects. The spiking neural network incorporates two kinetically different GABA(A receptor-mediated currents to generate both theta and gamma rhythms and we have found that by selective alteration of both NMDA receptors and GABA(A,slow receptors it can reproduce learning-related changes in the strength of coupling between theta and gamma either with or without coincident changes in theta amplitude. When the model was used to explore the relationship between theta and gamma oscillations, working memory capacity and phase coding it showed that the potential storage capacity of short term memories, in terms of nested gamma-subcycles, coincides with the maximal theta power. Increasing theta power is also related to the precision of theta phase which functions as a potential timing clock for neuronal firing in the cortex or hippocampus.

Transcranial Direct Current Stimulation and Power Spectral Parameters: a tDCS/EEG co-registration study

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Anna Lisa Mangia

2014-08-01

Full Text Available Transcranial direct current stimulation (tDCS delivers low electric currents to the brain through the scalp. Constant electric currents induce shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Concomitant electroencephalography (EEG monitoring during tDCS can provide valuable information on the tDCS mechanisms of action. This study examined the effects of anodal tDCS on spontaneous cortical activity in a resting brain to disclose possible modulation of spontaneous oscillatory brain activity. EEG activity was measured in ten healthy subjects during and after a session of anodal stimulation of the postero-parietal cortex to detect the tDCS-induced alterations. Changes in the theta, alpha, beta and gamma power bands were investigated. Three main findings emerged: 1 an increase in theta band activity during the first minutes of stimulation; 2 an increase in alpha and beta power during and after stimulation; 3 a widespread activation in several brain regions.

Mimicking the brain: evaluation of St Jude Medical's Prodigy Chronic Pain System with Burst Technology.

Science.gov (United States)

De Ridder, Dirk; Vanneste, Sven; Plazier, Mark; Vancamp, Tim

2015-03-01

The Prodigy is a new type of internal pulse generator that controls the delivery of electrical stimuli to nervous tissue. It is capable of delivering burst stimulation, which is a novel waveform that consists of closely spaced high-frequency electrical impulses delivered in packets riding on a plateau, and followed by a quiescent period. Its inception was based on mimicking burst firing in the nervous system and usually delivered by unmyelinated fibers that uniformly have a motivational affective homeostatic function. It thereby targets a multimodal salience network, even though the stimuli are delivered at the level of the spinal cord. As such, it is specifically capable of influencing the affective/attentional components of pain. Burst stimulation was initially safely applied off-label to the auditory cortex for tinnitus, and later also to the spinal cord, the somatosensory cortex for neuropathic pain, subcutaneously for failed back surgery syndrome, and cingulate cortex for addiction and tinnitus.

Completely X-symmetric S-matrices corresponding to theta functions

International Nuclear Information System (INIS)

Chudnovsky, D.V.

1981-01-01

We consider the realization of the classical Weyl commutation relations using THETA-functions. The representations of the Heisenberg group enable us to realize completely symmetric factorized S-matrices in terms of THETA-functions corresponding to the torsion subgroup of an abelian variety. (orig.)

Cubic metaplectic forms and theta functions

CERN Document Server

Proskurin, Nikolai

1998-01-01

The book is an introduction to the theory of cubic metaplectic forms on the 3-dimensional hyperbolic space and the author's research on cubic metaplectic forms on special linear and symplectic groups of rank 2. The topics include: Kubota and Bass-Milnor-Serre homomorphisms, cubic metaplectic Eisenstein series, cubic theta functions, Whittaker functions. A special method is developed and applied to find Fourier coefficients of the Eisenstein series and cubic theta functions. The book is intended for readers, with beginning graduate-level background, interested in further research in the theory of metaplectic forms and in possible applications.

Chasing theta-13 with the Double Chooz experiment

Energy Technology Data Exchange (ETDEWEB)

Lasserre, Thierry [CEA/DSM/IRFU/SPP, Gif-sur-Yvette (France)

2009-07-01

Neutrino oscillation physics is entering a precision measurement area. The smallness of the theta-13 neutrino mixing angle is still enigmatic and should be resolved. Double Chooz will use two identical detectors near the Chooz nuclear power station to search for a non vanishing theta-13, and hopefully open the way to experiments aspiring to discover CP violation in the leptonic sector.

Some theorems on the explicit evaluation of Ramanujan's theta-functions

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Nayandeep Deka Baruah

2004-01-01

Full Text Available Bruce C. Berndt et al. and Soon-Yi Kang have proved many of Ramanujan's formulas for the explicit evaluation of the Rogers-Ramanujan continued fraction and theta-functions in terms of Weber-Ramanujan class invariants. In this note, we give alternative proofs of some of these identities of theta-functions recorded by Ramanujan in his notebooks and deduce some formulas for the explicit evaluation of his theta-functions in terms of Weber-Ramanujan class invariants.

Fluctuating inhibitory inputs promote reliable spiking at theta frequencies in hippocampal interneurons

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Duluxan eSritharan

2012-05-01

Full Text Available Theta frequency (4-12 Hz rhythms in the hippocampus play important roles in learning and memory. CA1 interneurons located at the stratum lacunosum-moleculare and radiatum junction (LM/RAD are thought to contribute to hippocampal theta population activities by rhythmically pacing pyramidal cells with inhibitory postsynaptic potentials. This implies that LM/RAD cells need to fire reliably at theta frequencies in vivo. To determine whether this could occur, we use biophysically-based LM/RAD model cells and apply different cholinergic and synaptic inputs to simulate in vivo-like network environments. We assess spike reliabilities and spiking frequencies, identifying biophysical properties and network conditions that best promote reliable theta spiking. We find that synaptic background activities that feature large inhibitory, but not excitatory, fluctuations are essential. This suggests that strong inhibitory input to these cells is vital for them to be able to contribute to population theta activities. Furthermore, we find that Type I-like oscillator models produced by augmented persistent sodium currents (INap or diminished A type potassium currents (IA enhance reliable spiking at lower theta frequencies. These Type I-like models are also the most responsive to large inhibitory fluctuations and can fire more reliably under such conditions. In previous work, we showed that INap and IA are largely responsible for establishing LM/RAD cells’ subthreshold activities. Taken together with this study, we see that while both these currents are important for subthreshold theta fluctuations and reliable theta spiking, they contribute in different ways – INap to reliable theta spiking and subthreshold activity generation, and IA to subthreshold activities at theta frequencies. This suggests that linking subthreshold and suprathreshold activities should be done with consideration of both in vivo contexts and biophysical specifics.

Adaptive [theta]-methods for pricing American options

Science.gov (United States)

Khaliq, Abdul Q. M.; Voss, David A.; Kazmi, Kamran

2008-12-01

We develop adaptive [theta]-methods for solving the Black-Scholes PDE for American options. By adding a small, continuous term, the Black-Scholes PDE becomes an advection-diffusion-reaction equation on a fixed spatial domain. Standard implementation of [theta]-methods would require a Newton-type iterative procedure at each time step thereby increasing the computational complexity of the methods. Our linearly implicit approach avoids such complications. We establish a general framework under which [theta]-methods satisfy a discrete version of the positivity constraint characteristic of American options, and numerically demonstrate the sensitivity of the constraint. The positivity results are established for the single-asset and independent two-asset models. In addition, we have incorporated and analyzed an adaptive time-step control strategy to increase the computational efficiency. Numerical experiments are presented for one- and two-asset American options, using adaptive exponential splitting for two-asset problems. The approach is compared with an iterative solution of the two-asset problem in terms of computational efficiency.

Molecular cloning of rock bream (Oplegnathus fasciatus) tumor necrosis factor-alpha and its effect on the respiratory burst activity of phagocytes.

Science.gov (United States)

Kim, Min Sun; Hwang, Yoon Jung; Yoon, Ki Joon; Zenke, Kosuke; Nam, Yoon Kwon; Kim, Sung Koo; Kim, Ki Hong

2009-11-01

Rock bream (Oplegnathus fasciatus) tumor necrosis factor-alpha (rbTNF-alpha) gene was cloned, recombinantly produced, and the effect of the recombinant rbTNF-alpha on the respiratory burst activity of rock bream phagocytes was analyzed. Structurally, genomic DNA of rbTNF-alpha was comprised with four exons and three introns, and deduced amino acid sequence of its cDNA possessed the TNF family signature, a transmembrane domain, a protease cleavage site, and two cysteine residues, which are the typical characteristics of TNF-alpha gene in mammals and fish. The chemiluminescent (CL) response of rock bream phagocytes was significantly enhanced by pre-incubation with recombinant rbTNF-alpha, when opsonized zymosan was used as a stimulant of the respiratory burst. However, CL enhancing effect of the recombinant rbTNF-alpha was very weak when the respiratory burst activity of phagocytes was triggered with phorbol-12-myristate-13-acetate (PMA) instead of zymosan. These results suggest that rock bream TNF-alpha might have an ability to prime the respiratory burst activity of phagocytes against receptor-mediated phagocytosis inducing stimulants, such as zymosan, but have little ability against stimulants not accompanying receptor-mediated phagocytosis.

Eisenstein Series Identities Involving the Borweins' Cubic Theta Functions

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Ernest X. W. Xia

2012-01-01

Full Text Available Based on the theories of Ramanujan's elliptic functions and the (p, k-parametrization of theta functions due to Alaca et al. (2006, 2007, 2006 we derive certain Eisenstein series identities involving the Borweins' cubic theta functions with the help of the computer. Some of these identities were proved by Liu based on the fundamental theory of elliptic functions and some of them may be new. One side of each identity involves Eisenstein series, the other products of the Borweins' cubic theta functions. As applications, we evaluate some convolution sums. These evaluations are different from the formulas given by Alaca et al.

Mast cell granules modulate alveolar macrophage respiratory-burst activity and eicosanoid metabolism.

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Rock, M J; Despot, J; Lemanske, R F

1990-10-01

Alveolar macrophages (AMs) and mast cells reside in the airway, and both have been demonstrated to contribute independently to allergic inflammatory responses through the generation of respiratory-burst metabolites and the release of biologically active mediators, respectively. Since mast cell granules (MCGs) contain mediators that could potentially interact with the AM respiratory burst, we investigated the effects of isolated MCGs on this important inflammatory pathway of the AM. MCGs and AMs were obtained by peritoneal and tracheoalveolar lavage, respectively, of Sprague-Dawley rats. First, the overall respiratory-burst activity was measured by luminal-enhanced chemiluminescence (CL), and second, the individual oxygen species contributing to CL (superoxide anion [O2-], hydrogen peroxide [H2O2], and hypochlorous acid) were measured. MCGs alone enhanced AM CL responses to an equivalent degree compared to zymosan-stimulated AMs. However, AMs preincubated with MCGs followed by zymosan stimulation significantly and synergistically enhanced the CL responses. This enhanced CL was not due to an increased production of O2-, H2O2, or hypochlorous acid; in fact, there were decreased measured amounts of O2- and H2O2 from zymosan-stimulated AMs in the presence of MCGs, most likely caused by the content of granules of superoxide dismutase and peroxidase, respectively. The lipoxygenase inhibitor, nordihydroguaiaretic acid, completely abolished the enhanced CL of AM preincubated with MCGs and subsequently stimulated by zymosan, but O2- production was not affected by nordihydroguaiaretic acid. Taken together, these results suggest that derivatives of arachidonic acid metabolism, most likely those of the lipoxygenase pathway, are responsible for the enhanced AM CL response observed in the presence of MCGs. Thus, mast cell-macrophage interactions may be important within the airway in enhancing the generation of mediators that contribute to tissue inflammation and bronchospasm.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat.

Science.gov (United States)

Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

2015-04-21

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation.

Electrically induced contraction levels of the quadriceps femoris muscles in healthy men: the effects of three patterns of burst-modulated alternating current and volitional muscle fatigue.

Science.gov (United States)

Parker, Michael G; Broughton, Alex J; Larsen, Ben R; Dinius, Josh W; Cimbura, Mac J; Davis, Matthew

2011-12-01

The purpose of this study was to compare electrically induced contraction levels produced by three patterns of alternating current in fatigued and nonfatigued skeletal muscles. Eighteen male volunteers without health conditions, with a mean (SD) age of 24.9 (3.4) yrs were randomly exposed to a fatiguing volitional isometric quadriceps contraction and one of three patterns of 2.5-KHz alternating current; two were modulated at 50 bursts per second (10% burst duty cycle with five cycles per burst and 90% burst duty cycle with 45 cycles per burst), and one pattern was modulated at 100 bursts per second (10% burst duty cycle with 2.5 cycles per burst). The electrically induced contraction levels produced by the three patterns of electrical stimulation were compared before and after the fatiguing contraction. The 10% burst duty cycles produced 42.9% (95% confidence interval, 29.1%-56.7%) and 32.1% (95% confidence interval, 18.2%-45.9%) more muscle force (P stronger muscle contractions. Furthermore, the stimulation patterns had no influence on the difference in muscle force before and after the fatiguing quadriceps contraction. Consequently, for clinical applications in which high forces are desired, the patterns using the 10% burst duty cycle may be helpful.

Torus C-I field reversed theta-pinch at UNICAMP

International Nuclear Information System (INIS)

Machida, M.; Collares, M.P.; Honda, R.Y.; Sakanaka, P.H.; Scheid, V.H.B.

1984-01-01

The influence of multipole fields (octopole and quadrupole) on supressing the n=2 rotational instability, field reconnection, particle loss effects is studied, and the viability of transforming the theta-pinch from Campinas, Brazil (100Kv, 55Kj) to the field reversed theta-pinch with plasma translation program is analyzed. (E.G.) [pt

Human spinal locomotor control is based on flexibly organized burst generators

OpenAIRE

Danner, Simon M.; Hofstoetter, Ursula S.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

2015-01-01

Understanding the organisation of human spinal locomotor circuitry after severe CNS damage is essential for improving neurorehabilitation strategies. Danner et al. present evidence of flexibly organised burst-generating elements within the functionally isolated human lumbosacral spinal cord that generate rhythmic patterns in response to constant, repetitive epidural stimulation.

Cosmic gamma-ray burst

International Nuclear Information System (INIS)

Yamagami, Takamasa

1985-01-01

Ballon experiments for searching gamma-ray burst were carried out by employing rotating-cross modulation collimators. From a very long observation of total 315 hours during 1975 to 1979, three gamma-ray intensity anomalies were observed which were speculated as a gamma-ray burst. As for the first gamma-ray intensity anomaly observed in 1975, the burst source could be located precisely but the source, heavenly body, could not be specified. Gamma-ray burst source estimation was made by analyzing distribution of burst source in the celestial sphere, burst size distribution, and burst peak. Using the above-mentioned data together with previously published ones, apparent inconsistency was found between the observed results and the adopted theory that the source was in the Galaxy, and this inconsistency was found due to the different time profiles of the burst observed with instruments of different efficiency. It was concluded by these analysis results that employment of logN - logP (relation between burst frequency and burst count) was better than that of logN - logS (burst size) in the examination of gamma-ray burst because the former was less uncertain than the latter. Analyzing the author's observed gamma-ray burst data and the related published data, it was clarified that the burst distribution was almost P -312 for the burst peak value larger than 10 -6 erg/cm 2 .sec. The author could indicate that the calculated celestial distribution of burst source was consistent with the observed results by the derivation using the logN - logP relationship and that the burst larger than 10 -6 erg/cm 2 .sec happens about one thousand times a year, about ten times of the previous value. (Takagi, S.)

Stage theta pinch experiments

International Nuclear Information System (INIS)

Linford, R.K.; Downing, J.N.; Gribble, R.F.; Jacobson, A.R.; Platts, D.A.; Thomas, K.S.

1975-01-01

The Staged Theta Pinch program is designed to study the technological and physics problems associated with producing fat plasmas and separating the implosion heating from the adiabatic compression. Several methods of implosion heating are discussed. Circuit diagrams and theoretical magnetic field behavior are described for the STP and resonant heating experiments. (MOW)

C2 subcutaneous stimulation for failed back surgery syndrome: a case report.

Science.gov (United States)

De Ridder, Dirk; Plazier, Mark; Menovsky, Tomas; Kamerling, Niels; Vanneste, Sven

2013-01-01

Failed back surgery syndrome (FBSS) is a term embracing a constellation of conditions that describes persistent or recurring low back pain, with or without sciatica following one or more spine surgeries. It has been shown in animals that electrical stimulation of the high cervical C2 area can suppress pain stimuli derived from the L5-S1 dermatome. It is unknown whether C2 electrical stimulation in humans can be used to treat pain derived from the L5-S1 area, and a case is reported in which subcutaneous C2 is applied to treat FBSS. A patient presents to the neuromodulation clinic because of FBSS (after three lumbar diskectomies) and noninvasive neuromodulation is performed consisting of transcutaneous electrical nerve stimulation (TENS) at C2. The C2 TENS stimulation is successful in improving pain. It induces paresthesias in the C2 dermatome above a certain amplitude threshold, but does not generate paresthesias in the pain area. However, the patient becomes allergic to the skin-applied TENS electrodes and therefore a new treatment strategy is discussed with the patient. A subcutaneous C2 electrode is inserted under local anesthesia, and attached to an external pulse generator. Three stimulation designs are tested: a classical tonic stimulation, consisting of 40 Hz stimulation, a placebo, and a burst stimulation, consisting of 40 Hz burst mode, with five spikes delivered at 500 Hz at 1000 μsec pulse width and 1000 μsec interspike interval. The patient's stimulation results demonstrate that burst mode is superior to placebo and tonic mode, and she receives a fully implanted C2 electrode connected to an internal pulse generator via an extension wire. The burst design is capable of both suppressing the least and worst pain effectively, and she has remained almost pain-free for over three years. © 2012 International Neuromodulation Society.

Swift pointing and gravitational-wave bursts from gamma-ray burst events

International Nuclear Information System (INIS)

Sutton, Patrick J; Finn, Lee Samuel; Krishnan, Badri

2003-01-01

The currently accepted model for gamma-ray burst phenomena involves the violent formation of a rapidly rotating solar-mass black hole. Gravitational waves should be associated with the black-hole formation, and their detection would permit this model to be tested. Even upper limits on the gravitational-wave strength associated with gamma-ray bursts could constrain the gamma-ray burst model. This requires joint observations of gamma-ray burst events with gravitational and gamma-ray detectors. Here we examine how the quality of an upper limit on the gravitational-wave strength associated with gamma-ray bursts depends on the relative orientation of the gamma-ray-burst and gravitational-wave detectors, and apply our results to the particular case of the Swift Burst-Alert Telescope (BAT) and the LIGO gravitational-wave detectors. A result of this investigation is a science-based 'figure of merit' that can be used, together with other mission constraints, to optimize the pointing of the Swift telescope for the detection of gravitational waves associated with gamma-ray bursts

SOA thresholds for the perception of discrete/continuous tactile stimulation

DEFF Research Database (Denmark)

Eid, Mohamad; Korres, Georgios; Jensen, Camilla Birgitte Falk

In this paper we present an experiment to measure the upper and lower thresholds of the Stimulus Onset Asynchrony (SOA) for continuous/discrete apparent haptic motion. We focus on three stimulation parameters: the burst duration, the SOA time, and the inter-actuator distance (between successive......-discrete boundary at lower SOA. Furthermore, the larger the inter-actuator distance, the more linear the relationship between the burst duration and the SOA timing. Finally, the large range between lower and upper thresholds for SOA can be utilized to create continuous movement stimulation on the skin at “varying...... speeds”. The results are discussed in reference to designing a tactile interface for providing continuous haptic motion with a desired speed of continuous tactile stimulation....

Riemann-Theta Boltzmann Machine arXiv

CERN Document Server

Krefl, Daniel; Haghighat, Babak; Kahlen, Jens

A general Boltzmann machine with continuous visible and discrete integer valued hidden states is introduced. Under mild assumptions about the connection matrices, the probability density function of the visible units can be solved for analytically, yielding a novel parametric density function involving a ratio of Riemann-Theta functions. The conditional expectation of a hidden state for given visible states can also be calculated analytically, yielding a derivative of the logarithmic Riemann-Theta function. The conditional expectation can be used as activation function in a feedforward neural network, thereby increasing the modelling capacity of the network. Both the Boltzmann machine and the derived feedforward neural network can be successfully trained via standard gradient- and non-gradient-based optimization techniques.

Effect of Low-Level Laser Stimulation on EEG

Directory of Open Access Journals (Sweden)

Jih-Huah Wu

2012-01-01

Full Text Available Conventional laser stimulation at the acupoint can induce significant brain activation, and the activation is theoretically conveyed by the sensory afferents. Whether the insensible low-level Laser stimulation outside the acupoint could also evoke electroencephalographic (EEG changes is not known. We designed a low-level laser array stimulator (6 pcs laser diode, wavelength 830 nm, output power 7 mW, and operation frequency 10 Hz to deliver insensible laser stimulations to the palm. EEG activities before, during, and after the laser stimulation were collected. The amplitude powers of each EEG frequency band were analyzed. We found that the low-level laser stimulation was able to increase the power of alpha rhythms and theta waves, mainly in the posterior head regions. These effects lasted at least 15 minutes after cessation of the laser stimulation. The amplitude power of beta activities in the anterior head regions decreased after laser stimulation. We thought these EEG changes comparable to those in meditation.

Effect of low-level laser stimulation on EEG.

Science.gov (United States)

Wu, Jih-Huah; Chang, Wen-Dien; Hsieh, Chang-Wei; Jiang, Joe-Air; Fang, Wei; Shan, Yi-Chia; Chang, Yang-Chyuan

2012-01-01

Conventional laser stimulation at the acupoint can induce significant brain activation, and the activation is theoretically conveyed by the sensory afferents. Whether the insensible low-level Laser stimulation outside the acupoint could also evoke electroencephalographic (EEG) changes is not known. We designed a low-level laser array stimulator (6 pcs laser diode, wavelength 830 nm, output power 7 mW, and operation frequency 10 Hz) to deliver insensible laser stimulations to the palm. EEG activities before, during, and after the laser stimulation were collected. The amplitude powers of each EEG frequency band were analyzed. We found that the low-level laser stimulation was able to increase the power of alpha rhythms and theta waves, mainly in the posterior head regions. These effects lasted at least 15 minutes after cessation of the laser stimulation. The amplitude power of beta activities in the anterior head regions decreased after laser stimulation. We thought these EEG changes comparable to those in meditation.

Minocycline affects human neutrophil respiratory burst and transendothelial migration.

Science.gov (United States)

Parenti, Astrid; Indorato, Boris; Paccosi, Sara

2017-02-01

This study aimed at investigating the in vitro activity of minocycline and doxycycline on human polymorphonuclear (h-PMN) cell function. h-PMNs were isolated from whole venous blood of healthy subjects; PMN oxidative burst was measured by monitoring ROS-induced oxidation of luminol and transendothelial migration was studied by measuring PMN migration through a monolayer of human umbilical vein endothelial cells. Differences between multiple groups were determined by ANOVA followed by Tukey's multiple comparison test; Student's t test for unpaired data for two groups. Minocycline (1-300 µM) concentration dependently and significantly inhibited oxidative burst of h-PMNs stimulated with 100 nM fMLP. Ten micromolar concentrations, which are superimposable to C max following a standard oral dose of minocycline, promoted a 29.8 ± 4 % inhibition of respiratory burst (P minocycline impaired PMN transendothelial migration, with maximal effect at 100 µM (42.5 ± 7 %, inhibition, n = 5, P minocycline exerted on innate immune h-PMN cell function.

What is the functional relevance of prefrontal cortex entrainment to hippocampal theta rhythms?

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James Michael Hyman

2011-03-01

Full Text Available There has been considerable interest in the importance of oscillations in the brain and in how these oscillations relate to the firing of single neurons. Recently a number of studies have shown that the spiking of individual neurons in the medial prefrontal cortex (mPFC become entrained to the hippocampal (HPC theta rhythm. We recently showed that theta-entrained mPFC cells lost theta-entrainment specifically on error trials even though the firing rates of these cells did not change (Hyman et al., 2010. This implied that the level of HPC theta-entrainment of mPFC units was more predictive of trial outcome than differences in firing rates and that there is more information encoded by the mPFC on working memory tasks than can be accounted for by a simple rate code. Nevertheless, the functional meaning of mPFC entrainment to HPC theta remains a mystery. It is also unclear as to whether there are any differences in the nature of the information encoded by theta-entrained and non-entrained mPFC cells. In this review we discuss mPFC entrainment to HPC theta within the context of previous results as well as provide a more detailed analysis of the Hyman et al. (2010 data set. This re-analysis revealed that theta-entrained mPFC cells selectively encoded a variety of task relevant behaviors and stimuli while never theta-entrained mPFC cells were most strongly attuned to errors or the lack of expected rewards. In fact, these error responsive neurons were responsible for the error representations exhibited by the entire ensemble of mPFC neurons. A theta reset was also detected in the post-error period. While it is becoming increasingly evident that mPFC neurons exhibit correlates to virtually all cues and behaviors, perhaps phase-locking directs attention to the task-relevant representations required to solve a spatially based working memory task while the loss of theta-entrainment at the start of error trials may represent a shift of attention away from

1 Tb/s x km multimode fiber link combining WDM transmission and low-linewidth lasers.

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Gasulla, I; Capmany, J

2008-05-26

We have successfully demonstrated an error-free transmission of 10 x 20 Gb/s 200 GHz-spaced ITU channels through a 5 km link of 62.5-microm core-diameter graded-index multimode silica fiber. The overall figure corresponds to an aggregate bit rate per length product of 1 Tb/s x km, the highest value ever reported to our knowledge. Successful transmission is achieved by a combination of low-linewidth DFB lasers and the central launch technique.

Network and external perturbation induce burst synchronisation in cat cerebral cortex

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Lameu, Ewandson L.; Borges, Fernando S.; Borges, Rafael R.; Batista, Antonio M.; Baptista, Murilo S.; Viana, Ricardo L.

2016-05-01

The brain of mammals are divided into different cortical areas that are anatomically connected forming larger networks which perform cognitive tasks. The cat cerebral cortex is composed of 65 areas organised into the visual, auditory, somatosensory-motor and frontolimbic cognitive regions. We have built a network of networks, in which networks are connected among themselves according to the connections observed in the cat cortical areas aiming to study how inputs drive the synchronous behaviour in this cat brain-like network. We show that without external perturbations it is possible to observe high level of bursting synchronisation between neurons within almost all areas, except for the auditory area. Bursting synchronisation appears between neurons in the auditory region when an external perturbation is applied in another cognitive area. This is a clear evidence that burst synchronisation and collective behaviour in the brain might be a process mediated by other brain areas under stimulation.

Quantum key based burst confidentiality in optical burst switched networks.

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Balamurugan, A M; Sivasubramanian, A

2014-01-01

The optical burst switching (OBS) is an emergent result to the technology concern that could achieve a feasible network in future. They are endowed with the ability to meet the bandwidth requirement of those applications that require intensive bandwidth. There are more domains opening up in the OBS that evidently shows their advantages and their capability to face the future network traffic. However, the concept of OBS is still far from perfection facing issues in case of security threat. The transfer of optical switching paradigm to optical burst switching faces serious downfall in the fields of burst aggregation, routing, authentication, dispute resolution, and quality of service (QoS). This paper deals with employing RC4 (stream cipher) to encrypt and decrypt bursts thereby ensuring the confidentiality of the burst. Although the use of AES algorithm has already been proposed for the same issue, by contrasting the two algorithms under the parameters of burst encryption and decryption time, end-to-end delay, it was found that RC4 provided better results. This paper looks to provide a better solution for the confidentiality of the burst in OBS networks.

Quantum Key Based Burst Confidentiality in Optical Burst Switched Networks

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A. M. Balamurugan

2014-01-01

Full Text Available The optical burst switching (OBS is an emergent result to the technology concern that could achieve a feasible network in future. They are endowed with the ability to meet the bandwidth requirement of those applications that require intensive bandwidth. There are more domains opening up in the OBS that evidently shows their advantages and their capability to face the future network traffic. However, the concept of OBS is still far from perfection facing issues in case of security threat. The transfer of optical switching paradigm to optical burst switching faces serious downfall in the fields of burst aggregation, routing, authentication, dispute resolution, and quality of service (QoS. This paper deals with employing RC4 (stream cipher to encrypt and decrypt bursts thereby ensuring the confidentiality of the burst. Although the use of AES algorithm has already been proposed for the same issue, by contrasting the two algorithms under the parameters of burst encryption and decryption time, end-to-end delay, it was found that RC4 provided better results. This paper looks to provide a better solution for the confidentiality of the burst in OBS networks.

The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

DEFF Research Database (Denmark)

Minjoli, Sena; Saturnino, Guilherme B.; Blicher, Jakob Udby

2017-01-01

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large...... cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore....... Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative...

Recent developments in linear theta-pinch research: experiment and theory

International Nuclear Information System (INIS)

McKenna, K.F.; Bartsch, R.R.; Commisso, R.J.

1978-01-01

High energy plasmas offusion interest can be generated in linear theta pinches. However, end losses present a fundamental limitation on the plasma containment time. This paper discusses recent progress in end-loss and end-stoppering experiments and in the theoretical understanding of linear theta-pinch physics

Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

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Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

2013-10-01

Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

NMDA receptor subunits in the adult rat hippocampus undergo similar changes after 5 minutes in an open field and after LTP induction.

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Maria Veronica Baez

Full Text Available NMDA receptor subunits change during development and their synaptic expression is modified rapidly after synaptic plasticity induction in hippocampal slices. However, there is scarce information on subunits expression after synaptic plasticity induction or memory acquisition, particularly in adults. GluN1, GluN2A and GluN2B NMDA receptor subunits were assessed by western blot in 1 adult rats that had explored an open field (OF for 5 minutes, a time sufficient to induce habituation, 2 mature rat hippocampal neuron cultures depolarized by KCl and 3 hippocampal slices from adult rats where long term potentiation (LTP was induced by theta-burst stimulation (TBS. GluN1 and GluN2A, though not GluN2B, were significantly higher 70 minutes--but not 30 minutes--after a 5 minutes session in an OF. GluN1 and GluN2A total immunofluorescence and puncta in neurites increased in cultures, as evaluated 70 minutes after KCl stimulation. Similar changes were found in hippocampal slices 70 minutes after LTP induction. To start to explore underlying mechanisms, hippocampal slices were treated either with cycloheximide (a translation inhibitor or actinomycin D (a transcription inhibitor during electrophysiological assays. It was corroborated that translation was necessary for LTP induction and expression. The rise in GluN1 depends on transcription and translation, while the increase in GluN2A appears to mainly depend on translation, though a contribution of some remaining transcriptional activity during actinomycin D treatment could not be rouled out. LTP effective induction was required for the subunits to increase. Although in the three models same subunits suffered modifications in the same direction, within an apparently similar temporal course, further investigation is required to reveal if they are related processes and to find out whether they are causally related with synaptic plasticity, learning and memory.

Direct electrical stimulation using a battery-operated device for induction and modulation of colonic contractions in pigs.

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Bertschi, Mattia; Schlageter, Vincent; Vesin, Jean-Marc; Aellen, Steve; Peloponissios, Nicolas; D'Ambrogio, Aris; Wiesel, Paul Herman; Givel, Jean-Claude; Kucera, Pavel; Virag, Nathalie

2010-07-01

Direct electrical stimulation of the colon offers a promising approach for the induction of propulsive colonic contractions by using an implantable device. The objective of this study was to assess the feasibility to induce colonic contractions using a commercially available battery-operated stimulator (maximum pulse width of 1 ms and maximum amplitude of 10 V). Three pairs of pacing electrodes were inserted into the cecal seromuscular layer of anesthetized pigs. During a first set of in vivo experiments conducted on six animals, a pacing protocol leading to cecum contractions was determined: stimulation bursts with 1 ms pulse width, 10 V amplitude (7-15 mA), 120 Hz frequency, and 30-s burst duration, repeated every 2-5 min. In a second testing phase, an evaluation of the pacing protocol was performed in four animals (120 stimulation bursts in total). By using the battery-operated stimulator, contractions of the cecum and movement of contents could be induced in 92% of all stimulations. A cecal shortening of about 30% and an average intraluminal pressure increase of 10.0 +/- 6.0 mmHg were observed.