Low-frequency rTMS inhibitory effects in the primary motor cortex: Insights from TMS-evoked potentials.

PubMed

Casula, Elias P; Tarantino, Vincenza; Basso, Demis; Arcara, Giorgio; Marino, Giuliana; Toffolo, Gianna Maria; Rothwell, John C; Bisiacchi, Patrizia S

2014-09-01

The neuromodulatory effects of repetitive transcranial magnetic stimulation (rTMS) have been mostly investigated by peripheral motor-evoked potentials (MEPs). New TMS-compatible EEG systems allow a direct investigation of the stimulation effects through the analysis of TMS-evoked potentials (TEPs). We investigated the effects of 1-Hz rTMS over the primary motor cortex (M1) of 15 healthy volunteers on TEP evoked by single pulse TMS over the same area. A second experiment in which rTMS was delivered over the primary visual cortex (V1) of 15 healthy volunteers was conducted to examine the spatial specificity of the effects. Single-pulse TMS evoked four main components: P30, N45, P60 and N100. M1-rTMS resulted in a significant decrease of MEP amplitude and in a significant increase of P60 and N100 amplitude. There was no effect after V1-rTMS. 1-Hz rTMS appears to increase the amount of inhibition following a TMS pulse, as demonstrated by the higher N100 and P60, which are thought to originate from GABAb-mediated inhibitory post-synaptic potentials. Our results confirm the reliability of the TMS-evoked N100 as a marker of cortical inhibition and provide insight into the neuromodulatory effects of 1-Hz rTMS. The present finding could be of relevance for therapeutic and diagnostic purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

Targeted neural network interventions for auditory hallucinations: Can TMS inform DBS?

PubMed

Taylor, Joseph J; Krystal, John H; D'Souza, Deepak C; Gerrard, Jason Lee; Corlett, Philip R

2018-05-01

The debilitating and refractory nature of auditory hallucinations (AH) in schizophrenia and other psychiatric disorders has stimulated investigations into neuromodulatory interventions that target the aberrant neural networks associated with them. Internal or invasive forms of brain stimulation such as deep brain stimulation (DBS) are currently being explored for treatment-refractory schizophrenia. The process of developing and implementing DBS is limited by symptom clustering within psychiatric constructs as well as a scarcity of causal tools with which to predict response, refine targeting or guide clinical decisions. Transcranial magnetic stimulation (TMS), an external or non-invasive form of brain stimulation, has shown some promise as a therapeutic intervention for AH but remains relatively underutilized as an investigational probe of clinically relevant neural networks. In this editorial, we propose that TMS has the potential to inform DBS by adding individualized causal evidence to an evaluation processes otherwise devoid of it in patients. Although there are significant limitations and safety concerns regarding DBS, the combination of TMS with computational modeling of neuroimaging and neurophysiological data could provide critical insights into more robust and adaptable network modulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Safety study of high-frequency transcranial magnetic stimulation in patients with chronic stroke.

PubMed

Lomarev, M P; Kim, D Y; Richardson, S Pirio; Voller, B; Hallett, M

2007-09-01

Repetitive transcranial magnetic stimulation (rTMS) is a potential therapeutic tool to rehabilitate chronic stroke patients. In this study, the safety of high-frequency rTMS in stroke was investigated (Phase I). The safety of 20 and 25 Hz rTMS over the motor cortex (MC) of the affected hemisphere, with intensities of 110-130% of the motor threshold (MT), was evaluated using surface electromyography (EMG) of hand and arm muscles. Brief EMG bursts, possibly representing peripheral manifestations of after discharges, and spread of excitation to proximal muscles are considered to be associated with a high risk of seizure occurrence. These events were recorded after the rTMS trains. Neither increased MC excitability nor improved pinch force dynamometry was found after rTMS. Stimulation parameters for rTMS, which are safe for healthy volunteers, may lead to a higher risk for seizure occurrence in chronic stroke patients. rTMS at rates of 20 and 25 Hz using above threshold stimulation potentially increases the risk of seizures in patients with chronic stroke.

The right posterior inferior frontal gyrus contributes to phonological word decisions in the healthy brain: evidence from dual-site TMS.

PubMed

Hartwigsen, Gesa; Price, Cathy J; Baumgaertner, Annette; Geiss, Gesine; Koehnke, Maria; Ulmer, Stephan; Siebner, Hartwig R

2010-08-01

There is consensus that the left hemisphere plays a dominant role in language processing, but functional imaging studies have shown that the right as well as the left posterior inferior frontal gyri (pIFG) are activated when healthy right-handed individuals make phonological word decisions. Here we used online transcranial magnetic stimulation (TMS) to examine the functional relevance of the right pIFG for auditory and visual phonological decisions. Healthy right-handed individuals made phonological or semantic word judgements on the same set of auditorily and visually presented words while they received stereotactically guided TMS over the left, right or bilateral pIFG (n=14) or the anterior left, right or bilateral IFG (n=14). TMS started 100ms after word onset and consisted of four stimuli given at a rate of 10Hz and intensity of 90% of active motor threshold. Compared to TMS of aIFG, TMS of pIFG impaired reaction times and accuracy of phonological but not semantic decisions for visually and auditorily presented words. TMS over left, right or bilateral pIFG disrupted phonological processing to a similar degree. In a follow-up experiment, the intensity threshold for delaying phonological judgements was identical for unilateral TMS of left and right pIFG. These findings indicate that an intact function of right pIFG is necessary for accurate and efficient phonological decisions in the healthy brain with no evidence that the left and right pIFG can compensate for one another during online TMS. Our findings motivate detailed studies of phonological processing in patients with acute and chronic damage of the right pIFG. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Clinical outcomes and neural correlates of 20 sessions of repetitive transcranial magnetic stimulation in severe and enduring anorexia nervosa (the TIARA study): study protocol for a randomised controlled feasibility trial.

PubMed

Bartholdy, Savani; McClelland, Jessica; Kekic, Maria; O'Daly, Owen G; Campbell, Iain C; Werthmann, Jessica; Rennalls, Samantha J; Rubia, Katya; David, Anthony S; Glennon, Danielle; Kern, Nikola; Schmidt, Ulrike

2015-12-03

Anorexia nervosa (AN) is a serious mental disorder with multiple comorbidities and complications. In those with a severe and enduring form of the illness (SEED-AN), treatment responsivity is poor and the evidence base limited. Thus, there is a need for novel treatment strategies. This paper describes the theoretical background and protocol of a feasibility randomised controlled trial (RCT) of real versus sham (placebo) therapeutic repetitive transcranial magnetic stimulation (rTMS) in SEED-AN. The aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of rTMS in this group of patients, and also to assess the preliminary efficacy and neural correlates of rTMS treatment. Forty-four adults from the community with a DSM-5 diagnosis of AN, an illness duration>3 years and a previous course of unsuccessful treatment will be randomly allocated to receive 20 sessions of either real or sham rTMS, in a parallel group design. As this is a feasibility study, no primary outcome has been defined and a broad range of outcome variables will be examined. These include weight/body mass index (BMI), eating disorder psychopathology, other psychopathology (for example, depression, anxiety), quality of life, neuropsychological processes (such as self-regulation, attentional bias and food choice behaviour), neuroimaging measures (that is, changes in brain structure or function), tolerability and acceptability of rTMS, and additional service utilisation. The feasibility of conducting a large-scale RCT of rTMS and the appropriateness of rTMS as a treatment for SEED-AN will be evaluated through: assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up assessments). The acceptability and tolerability of the treatment will be assessed via semi-structured interviews. The effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. Additionally, results from this study will provide a preliminary indication of the efficacy of rTMS treatment for AN, the neural correlates of the illness, and potential biomarkers of clinical response. ISRCTN14329415 . Date of registration: 23 July 2015.

A practical guide to diagnostic transcranial magnetic stimulation: Report of an IFCN committee

PubMed Central

Groppa, S.; Oliviero, A.; Eisen, A.; Quartarone, A.; Cohen, L.G.; Mall, V.; Kaelin-Lang, A.; Mima, T.; Rossi, S.; Thickbroom, G.W.; Rossini, P.M.; Ziemann, U.; Valls-Solé, J.; Siebner, H.R.

2016-01-01

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS. PMID:22349304

Inhibitory rTMS applied on somatosensory cortex in Wilson's disease patients with hand dystonia.

PubMed

Lozeron, Pierre; Poujois, Aurélia; Meppiel, Elodie; Masmoudi, Sana; Magnan, Thierry Peron; Vicaut, Eric; Houdart, Emmanuel; Guichard, Jean-Pierre; Trocello, Jean-Marc; Woimant, France; Kubis, Nathalie

2017-10-01

Hand dystonia is a common complication of Wilson's disease (WD), responsible for handwriting difficulties and disability. Alteration of sensorimotor integration and overactivity of the somatosensory cortex have been demonstrated in dystonia. This study investigated the immediate after effect of an inhibitory repetitive transcranial magnetic stimulation (rTMS) applied over the somatosensory cortex on the writing function in WD patients with hand dystonia. We performed a pilot prospective randomized double-blind sham-controlled crossover rTMS study. A 20-min 1-Hz rTMS session, stereotaxically guided, was applied over the left somatosensory cortex in 13 WD patients with right dystonic writer's cramp. After 3 days, each patient was crossed-over to the alternative treatment. Patients were clinically evaluated before and immediately after each rTMS session with the Unified Wilson's Disease rating scale (UWDRS), the Writers' Cramp Rating Scale (WCRS), a specifically designed scale for handwriting difficulties in Wilson's disease patients (FAR, flow, accuracy, and rhythmicity evaluation), and a visual analog scale (VAS) for handwriting discomfort. No significant change in UWDRS, WCRS, VAS, or FAR scores was observed in patients treated with somatosensory inhibitory rTMS compared to the sham protocol. The FAR negatively correlated with UWDRS (r = -0.6; P = 0.02), but not with the WCRS score, disease duration, MRI diffusion lesions, or with atrophy scores. In our experimental conditions, a single inhibitory rTMS session applied over somatosensory cortex did not improve dystonic writer cramp in WD patients.

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

PubMed Central

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

2012-01-01

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

Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research

PubMed Central

Oberman, Lindsay M.; Enticott, Peter G.; Casanova, Manuel F.; Rotenberg, Alexander; Pascual-Leone, Alvaro; McCracken, James T.

2016-01-01

Autism Spectrum Disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by impairments in social communication, by the presence of restricted and repetitive behaviors, interests and activities, and by abnormalities in sensory reactivity. Transcranial magnetic stimulation (TMS) is a promising, emerging tool for the study and potential treatment of ASD. Recent studies suggest that TMS measures provide rapid and noninvasive pathophysiological ASD biomarkers. Furthermore, repetitive TMS (rTMS) may represent a novel treatment strategy for reducing some of the core and associated ASD symptoms. However, the available literature on the TMS use in ASD is preliminary, composed of studies with methodological limitations. Thus, off-label clinical rTMS use for therapeutic interventions in ASD without an investigational device exemption and outside of an IRB approved research trial is premature pending further, adequately powered and controlled trials. Leaders in this field have gathered annually for a two-day conference (prior to the 2014 and 2015 International Meeting for Autism Research, IMFAR) to share recent progress, promote collaboration across laboratories, and establish consensus on protocols. Here we review the literature in the use of TMS in ASD in the context of the unique challenges required for the study and exploration of treatment strategies in this population. We also suggest future directions for this field of investigations. While its true potential in ASD has yet to be delineated, TMS represents an innovative research tool and a novel, possibly transformative approach to the treatment of neurodevelopmental disorders. PMID:26536383

Probing feedforward and feedback contributions to awareness with visual masking and transcranial magnetic stimulation.

PubMed

Tapia, Evelina; Beck, Diane M

2014-01-01

A number of influential theories posit that visual awareness relies not only on the initial, stimulus-driven (i.e., feedforward) sweep of activation but also on recurrent feedback activity within and between brain regions. These theories of awareness draw heavily on data from masking paradigms in which visibility of one stimulus is reduced due to the presence of another stimulus. More recently transcranial magnetic stimulation (TMS) has been used to study the temporal dynamics of visual awareness. TMS over occipital cortex affects performance on visual tasks at distinct time points and in a manner that is comparable to visual masking. We draw parallels between these two methods and examine evidence for the neural mechanisms by which visual masking and TMS suppress stimulus visibility. Specifically, both methods have been proposed to affect feedforward as well as feedback signals when applied at distinct time windows relative to stimulus onset and as a result modify visual awareness. Most recent empirical evidence, moreover, suggests that while visual masking and TMS impact stimulus visibility comparably, the processes these methods affect may not be as similar as previously thought. In addition to reviewing both masking and TMS studies that examine feedforward and feedback processes in vision, we raise questions to guide future studies and further probe the necessary conditions for visual awareness.

Lasting effects of repeated rTMS application in focal hand dystonia.

PubMed

Borich, Michael; Arora, Sanjeev; Kimberley, Teresa Jacobson

2009-01-01

Focal hand dystonia (FHD) is a rare but potentially devastating disorder involving involuntary muscle spasms and abnormal posturing that impairs functional hand use. Increased cortical excitability and lack of inhibitory mechanisms have been associated with these symptoms. This study investigated the short- and long-term effects of repeated administrations of repetitive-transcranial magnetic stimulation (rTMS) on cortical excitability and handwriting performance. Six subjects with FHD and nine healthy controls were studied. All subjects with FHD received rTMS (1Hz) to the premotor cortex (PMC) for five consecutive days; of those, three subjects received five days of sham rTMS completed ten days prior to real treatment. Healthy subjects received one real rTMS session. Cortical silent period (CSP) and measures of handwriting performance were compared before and after treatment and at ten-day post-treatment follow-up. At baseline, significant differences in CSP and pen pressure were observed between subjects with FHD and healthy controls. Differences in CSP and pen velocity between subjects in real and sham rTMS groups were observed across treatment sessions and maintained at follow-up. After five days of rTMS to PMC, reduced cortical excitability and improved handwriting performance were observed and maintained at least ten days following treatment in subjects with FHD. These preliminary results support further investigation of the therapeutic potential of rTMS in FHD.

rTMS to the right inferior parietal lobule disrupts self–other discrimination

PubMed Central

Uddin, Lucina Q.; Molnar-Szakacs, Istvan; Zaidel, Eran; Iacoboni, Marco

2006-01-01

Self–other discrimination is fundamental to social interaction, however, little is known about the neural systems underlying this ability. In a previous functional magnetic resonance imaging study, we demonstrated that a right fronto-parietal network is activated during viewing of self-faces as compared with the faces of familiar others. Here we used image-guided repetitive transcranial magnetic stimulation (rTMS) to create a ‘virtual lesion’ over the parietal component of this network to test whether this region is necessary for discriminating self-faces from other familiar faces. The current results indeed show that 1 Hz rTMS to the right inferior parietal lobule (IPL) selectively disrupts performance on a self–other discrimination task. Applying 1 Hz rTMS to the left IPL had no effect. It appears that activity in the right IPL is essential to the task, thus providing for the first time evidence for a causal relation between a human brain area and this high-level cognitive capacity. PMID:17387382

Transcranial magnetic stimulation for the treatment of tinnitus: a new coil positioning method and first results.

PubMed

Langguth, Berthold; Zowe, Marc; Landgrebe, Michael; Sand, Philipp; Kleinjung, Tobias; Binder, Harald; Hajak, Göran; Eichhammer, Peter

2006-01-01

Auditory phantom perceptions are associated with hyperactivity of the central auditory system. Neuronavigation guided repetitive transcranial magnetic stimulation (rTMS) of the area of increased activity was demonstrated to reduce tinnitus perception. The study aimed at developing an easy applicable standard procedure for transcranial magnetic stimulation of the primary auditory cortex and to investigate this coil positioning strategy for the treatment of chronic tinnitus in clinical practice. The left gyrus of Heschl was targeted in 25 healthy subjects using a frameless stereotactical system. Based on individual scalp coordinates of the coil, a positioning strategy with reference to the 10--20-EEG system was developed. Using this coil positioning approach we started an open treatment trial. 28 patients with chronic tinnitus received 10 sessions of rTMS (intensity 110% of motor threshold, 1 Hz, 2000 Stimuli/day). Being within a range of about 20 mm diameter, the scalp coordinates for stimulating the primary auditory cortex allowed to determine a standard procedure for coil positioning. Clinical validation of this coil positioning method resulted in a significant improvement of tinnitus complaints (p<0.001). The newly developed coil positioning strategy may have the potential to offer a more easy-to-use stimulation approach for treating chronic tinnitus as compared with highly sophisticated, imaging guided treatment methods.

Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles—a TMS Study

PubMed Central

Sale, Martin V.; Rogasch, Nigel C.; Nordstrom, Michael A.

2016-01-01

The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs. PMID:27014031

Transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG): Biomarker of the future.

PubMed

Kimiskidis, V K

2016-02-01

In recent years, a number of novel brain-stimulation techniques have been developed (such as TMS-EEG, TMS-fMRI and TMS-NIRS), yet they remain underutilized in the field of epilepsy. Accumulating evidence suggests that transcranial magnetic stimulation (TMS) combined with electroencephalography (TMS-EEG) is a highly relevant technique for exploration of the pathophysiology of human epilepsies as well as a promising biomarker with diagnostic and prognostic potential. In genetic generalized epilepsies, TMS-EEG has provided pathophysiological insight by revealing quasi-stable, covert states of excitability, a subclass of which is associated with the generation of TMS-induced epileptiform discharges (EDs). In focal epilepsy, TMS-induced EDs were successfully employed to identify the epileptogenic zone. In addition, TMS trains applied during focal EDs can terminate them, and appear to restore the effective connectivity of the brain network significantly altered by EDs. This abortive effect of TMS on EDs may possibly serve as a biomarker of response to invasive neuromodulatory techniques. TMS-EEG-based stimulation paradigms can provide insight into the mechanisms underlying human epilepsies and, thus, warrant further study as diagnostic and prognostic biomarkers. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Neuromodulation integrating rTMS and neurofeedback for the treatment of autism spectrum disorder: an exploratory study.

PubMed

Sokhadze, Estate M; El-Baz, Ayman S; Tasman, Allan; Sears, Lonnie L; Wang, Yao; Lamina, Eva V; Casanova, Manuel F

2014-12-01

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social interaction, language, stereotyped behaviors, and restricted range of interests. In previous studies low frequency repetitive transcranial magnetic stimulation (rTMS) has been used, with positive behavioral and electrophysiological results, for the experimental treatment in ASD. In this study we combined prefrontal rTMS sessions with electroencephalographic (EEG) neurofeedback (NFB) to prolong and reinforce TMS-induced EEG changes. The pilot trial recruited 42 children with ASD (~14.5 years). Outcome measures included behavioral evaluations and reaction time test with event-related potential (ERP) recording. For the main goal of this exploratory study we used rTMS-neurofeedback combination (TMS-NFB, N = 20) and waitlist (WTL, N = 22) groups to examine effects of 18 sessions of integrated rTMS-NFB treatment or wait period) on behavioral responses, stimulus and response-locked ERPs, and other functional and clinical outcomes. The underlying hypothesis was that combined TMS-NFB will improve executive functions in autistic patients as compared to the WTL group. Behavioral and ERP outcomes were collected in pre- and post-treatment tests in both groups. Results of the study supported our hypothesis by demonstration of positive effects of combined TMS-NFB neurotherapy in active treatment group as compared to control WTL group, as the TMS-NFB group showed significant improvements in behavioral and functional outcomes as compared to the WTL group.

Neuromodulation integrating rTMS and neurofeedback for the treatment of autism spectrum disorder: An exploratory study

PubMed Central

Sokhadze, Estate M.; El-Baz, Ayman S.; Tasman, Allan; Sears, Lonnie L.; Wang, Yao; Lamina, Eva V.; Casanova, Manuel F.

2014-01-01

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social interaction, language, stereotyped behaviors, and restricted range of interests. In previous studies low frequency repetitive transcranial magnetic stimulation (rTMS) has been used, with positive behavioral and electrophysiological results, for the experimental treatment in ASD. In this study we combined prefrontal rTMS sessions with electroencephalographic (EEG) neurofeedback (NFB) to prolong and reinforce TMS-induced EEG changes. The pilot trial recruited 42 children with ASD (~14.5 yrs). Outcome measures included behavioral evaluations and reaction time test with event-related potential (ERP) recording. For the main goal of this exploratory study we used rTMS-neurofeedback combination (TMS-NFB, N=20) and waitlist (WTL, N=22) groups to examine effects of 18 sessions of integrated rTMS-NFB treatment or wait period) on behavioral responses, stimulus and response-locked ERPs, and other functional and clinical outcomes. The underlying hypothesis was that combined TMS-NFB will improve executive functions in autistic patients as compared to the waitlist group. Behavioral and ERP outcomes were collected in pre- and post-treatment tests in both groups. Results of the study supported our hypothesis by demonstration of positive effects of combined TMS-NFB neurotherapy in active treatment group as compared to control waitlist group, as the TMS-NFB group showed significant improvements in behavioral and functional outcomes as compared to the waitlist group. PMID:25267414

Combining near-infrared spectroscopy with electroencephalography and repetitive transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Näsi, Tiina; Kotilahti, Kalle; Mäki, Hanna; Nissilä, Ilkka; Meriläinen, Pekka

2009-07-01

The objective of the study was to assess the usability of a near-infrared spectroscopy (NIRS) device in multimodal measurements. We combined NIRS with electroencephalography (EEG) to record hemodynamic responses and evoked potentials simultaneously, and with transcranial magnetic stimulation (TMS) to investigate hemodynamic responses to repetitive TMS (rTMS). Hemodynamic responses and visual evoked potentials (VEPs) to 3, 6, and 12 s stimuli consisting of pattern-reversing checkerboards were successfully recorded in the NIRS/EEG measurement, and ipsi- and contralateral hemodynamic responses to 0.5, 1, and 2 Hz rTMS in the NIRS/TMS measurement. In the NIRS/EEG measurements, the amplitudes of the hemodynamic responses increased from 3- to 6-s stimulus, but not from 6- to 12-s stimulus, and the VEPs showed peaks N75, P100, and N135. In the NIRS/TMS measurements, the 2-Hz stimulus produced the strongest hemodynamic responses compared to the 0.5- and 1-Hz stimuli. In two subjects oxyhemoglobin concentration decreased and in one increased as a consequence of the 2-Hz rTMS. To locate the origin of the measured NIRS responses, methods have to be developed to investigate TMS-induced scalp muscle contractions. In the future, multimodal measurements may prove useful in monitoring or treating diseases such as stroke or Alzheimer's disease.

Probing feedforward and feedback contributions to awareness with visual masking and transcranial magnetic stimulation

PubMed Central

Tapia, Evelina; Beck, Diane M.

2014-01-01

A number of influential theories posit that visual awareness relies not only on the initial, stimulus-driven (i.e., feedforward) sweep of activation but also on recurrent feedback activity within and between brain regions. These theories of awareness draw heavily on data from masking paradigms in which visibility of one stimulus is reduced due to the presence of another stimulus. More recently transcranial magnetic stimulation (TMS) has been used to study the temporal dynamics of visual awareness. TMS over occipital cortex affects performance on visual tasks at distinct time points and in a manner that is comparable to visual masking. We draw parallels between these two methods and examine evidence for the neural mechanisms by which visual masking and TMS suppress stimulus visibility. Specifically, both methods have been proposed to affect feedforward as well as feedback signals when applied at distinct time windows relative to stimulus onset and as a result modify visual awareness. Most recent empirical evidence, moreover, suggests that while visual masking and TMS impact stimulus visibility comparably, the processes these methods affect may not be as similar as previously thought. In addition to reviewing both masking and TMS studies that examine feedforward and feedback processes in vision, we raise questions to guide future studies and further probe the necessary conditions for visual awareness. PMID:25374548

Brain stimulation over Broca’s area differentially modulates naming skills in neurotypical adults and individuals with Asperger’s syndrome

PubMed Central

Fecteau, Shirley; Agosta, Sara; Oberman, Lindsay; Pascual-Leone, Alvaro

2012-01-01

In the present study we tested the hypothesis that, in subjects with Asperger’s syndrome (ASP), the dynamics of language-related regions might be abnormal, so that repetitive transcranial magnetic stimulation (rTMS) over Broca’s area leads to differential behavioral effects as seen in neurotypical controls. We conducted a five-stimulation-site, double-blind, multiple crossover, pseudo-randomized, sham-controlled study in 10 individuals with ASP and 10 age- and gender-matched healthy subjects. Object naming was assessed before and after low-frequency rTMS of the left pars opercularis, left pars triangularis, right pars opercularis and right pars triangularis, and sham stimulation, as guided stereotaxically by each individual’s brain magnetic resonance imaging. In ASP participants, naming improved after rTMS of the left pars triangularis as compared with sham stimulation, whereas rTMS of the adjacent left opercularis lengthened naming latency. In healthy subjects, stimulation of parts of Broca’s area did not lead to significant changes in naming skills, consistent with published data. Overall, these findings support our hypothesis of abnormal language neural network dynamics in individuals with ASP. From a methodological point of view, this work illustrates the use of rTMS to study the dynamics of brain–behavior relations by revealing the differential behavioral impact of non-invasive brain stimulation in a neuropsychiatric disorder. PMID:21676037

rTMS in the treatment of drug addiction: an update about human studies.

PubMed

Bellamoli, Elisa; Manganotti, Paolo; Schwartz, Robert P; Rimondo, Claudia; Gomma, Maurizio; Serpelloni, Giovanni

2014-01-01

Drug addiction can be a devastating and chronic relapsing disorder with social, psychological, and physical consequences, and more effective treatment options are needed. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has been assessed in a growing number of studies for its therapeutic potential in treating addiction. This review paper offers an overview on the current state of clinical research in treating drug addiction with rTMS. Because of the limited research in this area, all studies (including case reports) that evaluated the therapeutic use of rTMS in nicotine, alcohol, or illicit drug addiction were included in this review. Papers published prior to December 2012 were found through an NCBI PubMed search. A total of eleven studies were identified that met review criteria. There is nascent evidence that rTMS could be effective in reducing cocaine craving and nicotine and alcohol craving and consumption and might represent a potential therapeutic tool for treating addiction. Further studies are needed to identify the optimal parameters of stimulation for the most effective treatment of drug addiction, to improve our comprehension of the treatment neurophysiological effects, and to conduct rigorous, controlled efficacy studies with adequate power.

Research with Transcranial Magnetic Stimulation in the Treatment of Aphasia

PubMed Central

Martin, Paula I; Naeser, Margaret A.; Ho, Michael; Treglia, Ethan; Kaplan, Elina; Baker, Errol H.; Pascual-Leone, Alvaro

2010-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been used to improve language behavior, including naming, in stroke patients with chronic, nonfluent aphasia. Part 1 of this paper reviews functional imaging studies related to language recovery in aphasia. Part 2 reviews the rationale for using rTMS to treat nonfluent aphasia (based on functional imaging); and presents our current rTMS protocol. We present language results from our rTMS studies, and imaging results from overt naming fMRI scans obtained pre- and post- a series of rTMS treatments. Part 3 presents results from a pilot study where rTMS treatments were followed immediately by constraint-induced language therapy. Part 4 reviews our diffusion tensor imaging study that examined possible connectivity of arcuate fasciculus to different parts of Broca’s area (pars triangularis, PTr; pars opercularis, POp); and to ventral premotor cortex (vPMC). The potential role of mirror neurons in R POp and vPMC in aphasia recovery is discussed. PMID:19818232

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids.

PubMed

Lamusuo, S; Hirvonen, J; Lindholm, P; Martikainen, I K; Hagelberg, N; Parkkola, R; Taiminen, T; Hietala, J; Helin, S; Virtanen, A; Pertovaara, A; Jääskeläinen, S K

2017-10-01

Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex has been shown to alleviate neuropathic pain. To investigate the possible neurobiological correlates of cortical neurostimulation for the pain relief. We studied the effects of M1/S1 rTMS on nociception, brain dopamine D2 and μ-opioid receptors using a randomized, sham-controlled, double-blinded crossover study design and 3D-positron emission tomography (PET). Ten healthy subjects underwent active and sham rTMS treatments to the right M1/S1 cortex with E-field navigated device. Dopamine D2 and μ-receptor availabilities were assessed with PET radiotracers [ 11 C]raclopride and [ 11 C]carfentanil after each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat evoked potential (CHEP) and blink reflex (BR) recordings were performed between the PET scans. μ-Opioid receptor availability was lower after active than sham rTMS (P ≤ 0.0001) suggested release of endogenous opioids in the right ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal cortex and precentral gyrus. There were no differences in striatal dopamine D2 receptor availability between active and sham rTMS, consistent with lack of long-lasting measurable dopamine release. Active rTMS potentiated the dopamine-regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP remained unchanged after active rTMS. rTMS given to M1/S1 activates the endogenous opioid system in a wide brain network associated with processing of pain and other salient stimuli. Direct enhancement of top-down opioid-mediated inhibition may partly explain the clinical analgesic effects of rTMS. Neurobiological correlates of rTMS for the pain relief are unclear. rTMS on M1/S1 with 11 C-carfentanyl-PET activates endogenous opioids. Thermal and heat pain thresholds remain unchanged. rTMS induces top-down opioid-mediated inhibition but not change the sensory discrimination of painful stimuli. © 2017 European Pain Federation - EFIC®.

Interhemispheric compensation: a hypothesis of TMS-induced effects on language-related areas.

PubMed

Andoh, Jamila; Martinot, Jean-Luc

2008-06-01

Repetitive transcranial magnetic stimulation (rTMS) applied over brain regions responsible for language processing is used to curtail potentially auditory hallucinations in schizophrenia patients and to investigate the functional organisation of language-related areas. Variability of effects is, however, marked across studies and between subjects. Furthermore, the mechanisms of action of rTMS are poorly understood. Here, we reviewed different factors related to the structural and functional organisation of the brain that might influence rTMS-induced effects. Then, by analogy with aphasia studies, and the plastic-adaptive changes in both the left and right hemispheres following aphasia recovery, a hypothesis is proposed about rTMS mechanisms over language-related areas (e.g. Wernicke, Broca). We proposed that the local interference induced by rTMS in language-related areas might be analogous to aphasic stroke and might lead to a functional reorganisation in areas connected to the virtual lesion for language recovery.

Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trial.

PubMed

Johnson, Kevin A; Baig, Mirza; Ramsey, Dave; Lisanby, Sarah H; Avery, David; McDonald, William M; Li, Xingbao; Bernhardt, Elisabeth R; Haynor, David R; Holtzheimer, Paul E; Sackeim, Harold A; George, Mark S; Nahas, Ziad

2013-03-01

Motor cortex localization and motor threshold determination often guide Transcranial Magnetic Stimulation (TMS) placement and intensity settings for non-motor brain stimulation. However, anatomic variability results in variability of placement and effective intensity. Post-study analysis of the OPT-TMS Study reviewed both the final positioning and the effective intensity of stimulation (accounting for relative prefrontal scalp-cortex distances). We acquired MRI scans of 185 patients in a multi-site trial of left prefrontal TMS for depression. Scans had marked motor sites (localized with TMS) and marked prefrontal sites (5 cm anterior of motor cortex by the "5 cm rule"). Based on a visual determination made before the first treatment, TMS therapy occurred either at the 5 cm location or was adjusted 1 cm forward. Stimulation intensity was 120% of resting motor threshold. The "5 cm rule" would have placed stimulation in premotor cortex for 9% of patients, which was reduced to 4% with adjustments. We did not find a statistically significant effect of positioning on remission, but no patients with premotor stimulation achieved remission (0/7). Effective stimulation ranged from 93 to 156% of motor threshold, and no seizures were induced across this range. Patients experienced remission with effective stimulation intensity ranging from 93 to 146% of motor threshold, and we did not find a significant effect of effective intensity on remission. Our data indicates that individualized positioning methods are useful to reduce variability in placement. Stimulation at 120% of motor threshold, unadjusted for scalp-cortex distances, appears safe for a broad range of patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of transcranial magnetic stimulation on force of finger pinch

NASA Astrophysics Data System (ADS)

Odagaki, Masato; Fukuda, Hiroshi; Hiwaki, Osamu

2009-04-01

Transcranial magnetic stimulation (TMS) is used to explore many aspects of brain function, and to treat neurological disorders. Cortical motor neuronal activation by TMS over the primary motor cortex (M1) produces efferent signals that pass through the corticospinal tracts. Motor-evoked potentials (MEPs) are observed in muscles innervated by the stimulated motor cortex. TMS can cause a silent period (SP) following MEP in voluntary electromyography (EMG). The present study examined the effects of TMS eliciting MEP and SP on the force of pinching using two fingers. Subjects pinched a wooden block with the thumb and index finger. TMS was applied to M1 during the pinch task. EMG of first dorsal interosseous muscles and pinch forces were measured. Force output increased after the TMS, and then oscillated. The results indicated that the motor control system to keep isotonic forces of the muscles participated in the finger pinch was disrupted by the TMS.

Low frequency rTMS over posterior parietal cortex impairs smooth pursuit eye tracking.

PubMed

Hutton, Samuel B; Weekes, Brendan S

2007-11-01

The role of the posterior parietal cortex in smooth pursuit eye movements remains unclear. We used low frequency repetitive transcranial magnetic stimulation (rTMS) to study the cognitive and neural systems involved in the control of smooth pursuit eye movements. Eighteen participants were tested on two separate occasions. On each occasion we measured smooth pursuit eye tracking before and after 6 min of 1 Hz rTMS delivered at 90% of motor threshold. Low frequency rTMS over the posterior parietal cortex led to a significant reduction in smooth pursuit velocity gain, whereas rTMS over the motor cortex had no effect on gain. We conclude that low frequency offline rTMS is a potentially useful tool with which to explore the cortical systems involved in oculomotor control.

What does low-intensity rTMS do to the cerebellum?

PubMed

Morellini, N; Grehl, S; Tang, A; Rodger, J; Mariani, J; Lohof, A M; Sherrard, R M

2015-02-01

Non-invasive stimulation of the human cerebellum, such as by transcranial magnetic stimulation (TMS), is increasingly used to investigate cerebellar function and identify potential treatment for cerebellar dysfunction. However, the effects of TMS on cerebellar neurons remain poorly defined. We applied low-intensity repetitive TMS (LI-rTMS) to the mouse cerebellum in vivo and in vitro and examined the cellular and molecular sequelae. In normal C57/Bl6 mice, 4 weeks of LI-rTMS using a complex biomimetic high-frequency stimulation (BHFS) alters Purkinje cell (PC) dendritic and spine morphology; the effects persist 4 weeks after the end of stimulation. We then evaluated whether LI-rTMS could induce climbing fibre (CF) reinnervation to denervated PCs. After unilateral pedunculotomy in adult mice and 2 weeks sham or BHFS stimulation, VGLUT2 immunohistochemistry was used to quantify CF reinnervation. In contrast to sham, LI-rTMS induced CF reinnervation to the denervated hemicerebellum. To examine potential mechanisms underlying the LI-rTMS effect, we verified that BHFS could induce CF reinnervation using our in vitro olivocerebellar explants in which denervated cerebellar tissue is co-cultured adjacent to intact cerebella and treated with brain-derived neurotrophic factor (BDNF) (as a positive control), sham or LI-rTMS for 2 weeks. Compared with sham, BDNF and BHFS LI-rTMS significantly increased CF reinnervation, without additive effect. To identify potential underlying mechanisms, we examined intracellular calcium flux during the 10-min stimulation. Complex high-frequency stimulation increased intracellular calcium by release from intracellular stores. Thus, even at low intensity, rTMS modifies PC structure and induces CF reinnervation.

Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation

NASA Astrophysics Data System (ADS)

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2015-08-01

Objective. Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response. Particularly, we sought to discover the E-field characteristics that lead to cortical activation. Approach. Subject-specific finite element models (FEMs) of the head and brain were constructed for each of six subjects using magnetic resonance image scans. Positron emission tomography (PET) measured each subject’s cortical response to image-guided robotically-positioned TMS to the primary motor cortex. FEM models that employed the given coil position, orientation, and stimulus intensity in experimental applications of TMS were used to calculate the electric field (E-field) vectors within a region of interest for each subject. TMS-induced E-fields were analyzed to better understand what vector components led to regional cerebral blood flow (CBF) responses recorded by PET. Main results. This study found that decomposing the E-field into orthogonal vector components based on the cortical surface geometry (and hence, cortical neuron directions) led to significant differences between the regions of cortex that were active and nonactive. Specifically, active regions had significantly higher E-field components in the normal inward direction (i.e., parallel to pyramidal neurons in the dendrite-to-axon orientation) and in the tangential direction (i.e., parallel to interneurons) at high gradient. In contrast, nonactive regions had higher E-field vectors in the outward normal direction suggesting inhibitory responses. Significance. These results provide critical new understanding of the factors by which TMS induces cortical activation necessary for predictive and repeatable use of this noninvasive stimulation modality.

Improvements in symptoms following neuronavigated repetitive transcranial magnetic stimulation (rTMS) in severe and enduring anorexia nervosa: findings from two case studies.

PubMed

McClelland, Jessica; Bozhilova, Natali; Nestler, Steffen; Campbell, Iain C; Jacob, Shirabdi; Johnson-Sabine, Eric; Schmidt, Ulrike

2013-11-01

Advances in the treatment of anorexia nervosa (AN) are most likely to arise from targeted, brain-directed treatments, such as repetitive transcranial magnetic stimulation (rTMS). We describe findings from two individuals with treatment-resistant AN who received 19-20 sessions of neuronavigated, high frequency rTMS, applied to the left dorsolateral prefrontal cortex. Within-session measures assessed changes pre-rTMS, post-rTMS in subjective eating disorder (ED) experiences. Weight, ED symptoms and mood were assessed pre-treatment, post-treatment and at 1 month follow-up. In both cases, there was improvement in ED symptomatology and mood after 19-20 sessions of neuronavigated rTMS, and these changes persisted or continued to improve at follow-up. Within sessions, Patient A demonstrated a consistent reduction in subjective ED experiences, and Patient B a reduction in some ED related experiences. These findings suggest that rTMS has potential as an adjunct to the treatment of AN and deserves further study. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

Resting state brain dynamics and its transients: a combined TMS-EEG study.

PubMed

Bonnard, Mireille; Chen, Sophie; Gaychet, Jérôme; Carrere, Marcel; Woodman, Marmaduke; Giusiano, Bernard; Jirsa, Viktor

2016-08-04

The brain at rest exhibits a spatio-temporally rich dynamics which adheres to systematic behaviours that persist in task paradigms but appear altered in disease. Despite this hypothesis, many rest state paradigms do not act directly upon the rest state and therefore cannot confirm hypotheses about its mechanisms. To address this challenge, we combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to study brain's relaxation toward rest following a transient perturbation. Specifically, TMS targeted either the medial prefrontal cortex (MPFC), i.e. part of the Default Mode Network (DMN) or the superior parietal lobule (SPL), involved in the Dorsal Attention Network. TMS was triggered by a given brain state, namely an increase in occipital alpha rhythm power. Following the initial TMS-Evoked Potential, TMS at MPFC enhances the induced occipital alpha rhythm, called Event Related Synchronisation, with a longer transient lifetime than TMS at SPL, and a higher amplitude. Our findings show a strong coupling between MPFC and the occipital alpha power. Although the rest state is organized around a core of resting state networks, the DMN functionally takes a special role among these resting state networks.

Effects of low-frequency repetitive transcranial magnetic stimulation on event-related potential P300

NASA Astrophysics Data System (ADS)

Torii, Tetsuya; Sato, Aya; Iwahashi, Masakuni; Iramina, Keiji

2012-04-01

The present study analyzed the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity. P300 latency of event-related potential (ERP) was used to evaluate the effects of low-frequency and short-term rTMS by stimulating the supramarginal gyrus (SMG), which is considered to be the related area of P300 origin. In addition, the prolonged stimulation effects on P300 latency were analyzed after applying rTMS. A figure-eight coil was used to stimulate left-right SMG, and intensity of magnetic stimulation was 80% of motor threshold. A total of 100 magnetic pulses were applied for rTMS. The effects of stimulus frequency at 0.5 or 1 Hz were determined. Following rTMS, an odd-ball task was performed and P300 latency of ERP was measured. The odd-ball task was performed at 5, 10, and 15 min post-rTMS. ERP was measured prior to magnetic stimulation as a control. Electroencephalograph (EEG) was measured at Fz, Cz, and Pz that were indicated by the international 10-20 electrode system. Results demonstrated that different effects on P300 latency occurred between 0.5-1 Hz rTMS. With 1 Hz low-frequency magnetic stimulation to the left SMG, P300 latency decreased. Compared to the control, the latency time difference was approximately 15 ms at Cz. This decrease continued for approximately 10 min post-rTMS. In contrast, 0.5 Hz rTMS resulted in delayed P300 latency. Compared to the control, the latency time difference was approximately 20 ms at Fz, and this delayed effect continued for approximately 15 min post-rTMS. Results demonstrated that P300 latency varied according to rTMS frequency. Furthermore, the duration of the effect was not similar for stimulus frequency of low-frequency rTMS.

Cortico-cortical and motor evoked potentials to single and paired-pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study.

PubMed

Boulogne, Sébastien; Andre-Obadia, Nathalie; Kimiskidis, Vasilios K; Ryvlin, Philippe; Rheims, Sylvain

2016-11-01

Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Investigating the Causal Role of rOFA in Holistic Detection of Mooney Faces and Objects: An fMRI-guided TMS Study.

PubMed

Bona, Silvia; Cattaneo, Zaira; Silvanto, Juha

2016-01-01

The right occipital face area (rOFA) is known to be involved in face discrimination based on local featural information. Whether this region is also involved in global, holistic stimulus processing is not known. We used fMRI-guided transcranial magnetic stimulation (TMS) to investigate whether rOFA is causally implicated in stimulus detection based on holistic processing, by the use of Mooney stimuli. Two studies were carried out: In Experiment 1, participants performed a detection task involving Mooney faces and Mooney objects; Mooney stimuli lack distinguishable local features and can be detected solely via holistic processing (i.e. at a global level) with top-down guidance from previously stored representations. Experiment 2 required participants to detect shapes which are recognized via bottom-up integration of local (collinear) Gabor elements and was performed to control for specificity of rOFA's implication in holistic detection. In Experiment 1, TMS over rOFA and rLO impaired detection of all stimulus categories, with no category-specific effect. In Experiment 2, shape detection was impaired when TMS was applied over rLO but not over rOFA. Our results demonstrate that rOFA is causally implicated in the type of top-down holistic detection required by Mooney stimuli and that such role is not face-selective. In contrast, rOFA does not appear to play a causal role in detection of shapes based on bottom-up integration of local components, demonstrating that its involvement in processing non-face stimuli is specific for holistic processing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

How can transcranial magnetic stimulation be used to causally manipulate memory representations in the human brain?

PubMed

Widhalm, Morgan L; Rose, Nathan S

2018-06-27

We present a focused review on the utility of transcranial magnetic stimulation (TMS) for modulating memory, with a particular focus on multimodal approaches in which TMS is paired with neuroimaging methods (electroencephalography and magnetic resonance imaging (MRI)) to manipulate and measure working memory processes. We contrast the utility of TMS for manipulating memory with other forms of noninvasive brain stimulation, as well as different forms of TMS including single-pulse, paired-pulse and repetitive TMS protocols. We discuss the potential for TMS to address fundamental cognitive neuroscience questions about the nature of memory processes and representations, while acknowledging the considerable variability of behavioral and neural outcomes in TMS studies. Also discussed are the limitations of this technology, current advancements that have helped to defray the impact of these limitations, and suggestions for future directions in research and methodology. This article is categorized under: Neuroscience > Clinical Neuroscience Neuroscience > Cognition Psychology > Memory. © 2018 Wiley Periodicals, Inc.

Teleoperator Maneuvering System (TMS) benefits assessment study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1983-01-01

Teleoperator Maneuvering System (TMS) versus integral spacecraft propulsion, spacecraft maintenance, cost benefits, launch prices, integral propulsion length penalties, remote maintenance versus EVA, potential weight reduction benefits, basing mode, mission models and payload requirements, and program profitability are discussed.

Preliminary Evidence of the Effects of High-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Swallowing Functions in Post-Stroke Individuals with Chronic Dysphagia

ERIC Educational Resources Information Center

Cheng, Ivy K. Y.; Chan, Karen M. K.; Wong, C. S.; Cheung, Raymond T. F.

2015-01-01

Background: There is growing evidence of potential benefits of repetitive transcranial magnetic stimulation (rTMS) in the rehabilitation of dysphagia. However, the site and frequency of stimulation for optimal effects are not clear. Aims: The aim of this pilot study is to investigate the short-term effects of high-frequency 5 Hz rTMS applied to…

Asymmetric activation of motor cortex controlling human anterior digastric muscles during speech and target-directed jaw movements.

PubMed

Sowman, Paul F; Flavel, Stanley C; McShane, Christie L; Sakuma, Shigemitsu; Miles, Timothy S; Nordstrom, Michael A

2009-07-01

Like most of the cranial muscles involved in speech, the trigeminally innervated anterior digastric muscles are controlled by descending corticobulbar projections from the primary motor cortex (M1) of each hemisphere. We hypothesized that changes in corticobulbar M1 excitability during speech production would show a hemispheric asymmetry favoring the left side, which is the dominant hemisphere for language processing in most strongly right handed subjects. Fifteen volunteers aged 24.5+/-5.3 (SD) yr participated. All subjects were strongly right handed as reported by questionnaire. A surface electromyograph (EMG) was recorded bilaterally from digastrics and jaw movement detected by an accelerometer attached to a lower incisor. Focal transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability of the digastric representation in M1 of both hemispheres during four tasks: 1) static isometric contraction of digastrics; 2) speaking a single word; 3) visually guided, nonspeech jaw movement that matched the jaw kinematics recorded during task 2; and 4) reciting a sentence. Background EMG was well matched in all tasks and jaw kinematics were similar around the time of the TMS pulse for tasks 2-4. TMS resting thresholds and digastric muscle-evoked potential (MEP) size during isometric contraction did not differ for TMS over left versus right M1. MEPs elicited by TMS over left, but not right M1 increased in size during speech and nonspeech jaw movement compared with isometric contraction. We conclude that left corticobulbar M1 is preferentially engaged for descending control of digastric muscles during speech and the performance of a rapid jaw movement to match a target kinematic profile.

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research☆

PubMed Central

Rossi, Simone; Hallett, Mark; Rossini, Paolo M.; Pascual-Leone, Alvaro

2011-01-01

This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7–9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible. PMID:19833552

The hydrogen sulfide metabolite trimethylsulfonium is found in human urine

NASA Astrophysics Data System (ADS)

Lajin, Bassam; Francesconi, Kevin A.

2016-06-01

Hydrogen sulfide is the third and most recently discovered gaseous signaling molecule following nitric oxide and carbon monoxide, playing important roles both in normal physiological conditions and disease progression. The trimethylsulfonium ion (TMS) can result from successive methylation reactions of hydrogen sulfide. No report exists so far about the presence or quantities of TMS in human urine. We developed a method for determining TMS in urine using liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (LC-ESI-QQQ), and applied the method to establish the urinary levels of TMS in a group of human volunteers. The measured urinary levels of TMS were in the nanomolar range, which is commensurate with the steady-state tissue concentrations of hydrogen sulfide previously reported in the literature. The developed method can be used in future studies for the quantification of urinary TMS as a potential biomarker for hydrogen sulfide body pools.

Transcranial Magnetic Stimulation to Address Mild Cognitive Impairment in the Elderly: A Randomized Controlled Study

PubMed Central

Drumond Marra, Hellen Livia; Myczkowski, Martin Luiz; Maia Memória, Cláudia; Arnaut, Débora; Leite Ribeiro, Philip; Sardinha Mansur, Carlos Gustavo; Lancelote Alberto, Rodrigo; Boura Bellini, Bianca; Alves Fernandes da Silva, Adriano; Ciampi de Andrade, Daniel; Teixeira, Manoel Jacobsen; Forlenza, Orestes Vicente; Marcolin, Marco Antonio

2015-01-01

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique with potential to improve memory. Mild cognitive impairment (MCI), which still lacks a specific therapy, is a clinical syndrome associated with increased risk of dementia. This study aims to assess the effects of high-frequency repetitive TMS (HF rTMS) on everyday memory of the elderly with MCI. We conducted a double-blinded randomized sham-controlled trial using rTMS over the left dorsolateral prefrontal cortex (DLPFC). Thirty-four elderly outpatients meeting Petersen's MCI criteria were randomly assigned to receive 10 sessions of either active TMS or sham, 10 Hz rTMS at 110% of motor threshold, 2,000 pulses per session. Neuropsychological assessment at baseline, after the last session (10th) and at one-month follow-up, was applied. ANOVA on the primary efficacy measure, the Rivermead Behavioural Memory Test, revealed a significant group-by-time interaction (p = 0.05), favoring the active group. The improvement was kept after one month. Other neuropsychological tests were heterogeneous. rTMS at 10 Hz enhanced everyday memory in elderly with MCI after 10 sessions. These findings suggest that rTMS might be effective as a therapy for MCI and probably a tool to delay deterioration. PMID:26160997

Effect of chronic and acute low-frequency repetitive transcranial magnetic stimulation on spatial memory in rats.

PubMed

Li, Wei; Yang, Yuye; Ye, Qing; Yang, Bo; Wang, Zhengrong

2007-03-15

Repetitive transcranial magnetic stimulation (rTMS) is a novel, non-invasive neurological and psychiatric tool. The low-frequency (1 Hz or less) rTMS is likely to play a particular role in its mechanism of action with different effects in comparison with high-frequency (>1 Hz) rTMS. There is limited information regarding the effect of low-frequency rTMS on spatial memory. In our study, each male Wistar rat was daily given 300 stimuli (1.0 T, 200 micros) at a rate of 0.5 Hz or sham stimulation. We investigated the effects of chronic and acute rTMS on reference/working memory process in Morris water maze test with the hypothesis that the effect would differ by chronic or acute condition. Chronic low-frequency rTMS impaired the retrieval of spatial short- and long-term spatial reference memory but not acquisition process and working memory, whereas acute low-frequency rTMS predominantly induced no deficits in acquisition or short-term spatial reference memory as well as working memory except for long-term reference memory. In summary, chronic 0.5 Hz rTMS disrupts spatial short- and long-term reference memory function, but acute rTMS differently affects reference memory. Chronic low-frequency rTMS may be used to modulate reference memory. Treatment protocols using low-frequency rTMS in neurological and psychiatric disorders need to take into account the potential effect of chronic low-frequency rTMS on memory and other cognitive functions.

A review of repetitive transcranial magnetic stimulation for adolescents with treatment-resistant depression.

PubMed

Magavi, Leela R; Reti, Irving M; Vasa, Roma A

2017-04-01

This review examines the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) as a treatment for treatment-resistant depression in adolescents. A systematic review of six databases was conducted. Ten multi-subject trials, all uncontrolled, and five case reports met inclusion criteria. Twelve studies focused on treatment efficacy, whereas three studies focused exclusively on adverse events. All efficacy studies focused on adolescents only; 10 of these studies indicated that rTMS may demonstrate some benefit. Improvement within 2-8 weeks was reported in most studies, with a few studies indicating potential long-term benefits. A variety of adverse events occurred including scalp pain, which was the most common, as well as seizures. Controlled studies of rTMS are warranted to further examine whether this treatment is a potential option for adolescents with treatment-resistant depression.

The Effectiveness of Transcranial Brain Stimulation in Improving Clinical Signs of Hyperkinetic Movement Disorders.

PubMed

Obeso, Ignacio; Cerasa, Antonio; Quattrone, Aldo

2015-01-01

Repetitive transcranial magnetic stimulation (rTMS) is a safe and painless method for stimulating cortical neurons. In neurological realm, rTMS has prevalently been applied to understand pathophysiological mechanisms underlying movement disorders. However, this tool has also the potential to be translated into a clinically applicable therapeutic use. Several available studies supported this hypothesis, but differences in protocols, clinical enrollment, and variability of rTMS effects across individuals complicate better understanding of efficient clinical protocols. The aim of this present review is to discuss to what extent the evidence provided by the therapeutic use of rTMS may be generalized. In particular, we attempted to define optimal cortical regions and stimulation protocols that have been demonstrated to maximize the effectiveness seen in the actual literature for the three most prevalent hyperkinetic movement disorders: Parkinson's disease (PD) with levodopa-induced dyskinesias (LIDs), essential tremor (ET) and dystonia. A total of 28 rTMS studies met our search criteria. Despite clinical and methodological differences, overall these studies demonstrated that therapeutic applications of rTMS to "normalize" pathologically decreased or increased levels of cortical activity have given moderate progress in patient's quality of life. Moreover, the present literature suggests that altered pathophysiology in hyperkinetic movement disorders establishes motor, premotor or cerebellar structures as candidate regions to reset cortico-subcortical pathways back to normal. Although rTMS has the potential to become a powerful tool for ameliorating the clinical outcome of hyperkinetic neurological patients, until now there is not a clear consensus on optimal protocols for these motor disorders. Well-controlled multicenter randomized clinical trials with high numbers of patients are urgently required.

Attention Modulates TMS-Locked Alpha Oscillations in the Visual Cortex

PubMed Central

Herring, Jim D.; Thut, Gregor; Jensen, Ole

2015-01-01

Cortical oscillations, such as 8–12 Hz alpha-band activity, are thought to subserve gating of information processing in the human brain. While most of the supporting evidence is correlational, causal evidence comes from attempts to externally drive (“entrain”) these oscillations by transcranial magnetic stimulation (TMS). Indeed, the frequency profile of TMS-evoked potentials (TEPs) closely resembles that of oscillations spontaneously emerging in the same brain region. However, it is unclear whether TMS-locked and spontaneous oscillations are produced by the same neuronal mechanisms. If so, they should react in a similar manner to top-down modulation by endogenous attention. To test this prediction, we assessed the alpha-like EEG response to TMS of the visual cortex during periods of high and low visual attention while participants attended to either the visual or auditory modality in a cross-modal attention task. We observed a TMS-locked local oscillatory alpha response lasting several cycles after TMS (but not after sham stimulation). Importantly, TMS-locked alpha power was suppressed during deployment of visual relative to auditory attention, mirroring spontaneous alpha amplitudes. In addition, the early N40 TEP component, located at the stimulation site, was amplified by visual attention. The extent of attentional modulation for both TMS-locked alpha power and N40 amplitude did depend, with opposite sign, on the individual ability to modulate spontaneous alpha power at the stimulation site. We therefore argue that TMS-locked and spontaneous oscillations are of common neurophysiological origin, whereas the N40 TEP component may serve as an index of current cortical excitability at the time of stimulation. SIGNIFICANCE STATEMENT Rhythmic transcranial magnetic stimulation (TMS) is a promising tool to experimentally “entrain” cortical activity. If TMS-locked oscillatory responses actually recruit the same neuronal mechanisms as spontaneous cortical oscillations, they qualify as a valid tool to study the causal role of neuronal oscillations in cognition but also to enable new treatments targeting aberrant oscillatory activity in, for example, neurological conditions. Here, we provide first-time evidence that TMS-locked and spontaneous oscillations are indeed tightly related and are likely to rely on the same neuronal generators. In addition, we demonstrate that an early local component of the TMS-evoked potential (the N40) may serve as a new objective and noninvasive probe of visual cortex excitability, which so far was only accessible via subjective phosphene reports. PMID:26511236

Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study.

PubMed

Terraneo, Alberto; Leggio, Lorenzo; Saladini, Marina; Ermani, Mario; Bonci, Antonello; Gallimberti, Luigi

2016-01-01

Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity, while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking, providing a strong rationale for applying brain stimulation to reduce cocaine consumption. Thus, we employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in humans. Thirty-two cocaine-addicted patients were randomly assigned to either the experimental group (rTMS) on the left DLPFC, or to a control group (pharmacological agents) during a 29-day study (Stage 1). This was followed by a 63-day follow-up (Stage 2), during which all participants were offered rTMS treatment. Amongst the patients who completed Stage 1, 16 were in the rTMS group (100%) and 13 in the control group (81%). No significant adverse events were noted. During Stage 1, there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control (p=0.004). Craving for cocaine was also significantly lower in the rTMS group compared to the controls (p=0.038). Out of 13 patients who completed Stage 1 in the control group, 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group. The present preliminary findings support the safety of rTMS in cocaine-addicted patients, and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use, providing a strong rationale for developing larger placebo-controlled studies. Trial name: Repetitive transcranial magnetic stimulation (rTMS) in cocaine abusers, URL:〈http://www.isrctn.com/ISRCTN15823943?q=&filters=&sort=&offset=8&totalResults=13530&page=1&pageSize=10&searchType=basic-search〉, ISRCTN15823943. Published by Elsevier B.V.

[Clinical applications of transcranial magnetic stimulation for the treatment of various neurological diseases].

PubMed

Tsuji, Sadatoshi

2005-11-01

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in various neurological and psychiatric diseases including depression, Parkinson disease, spinocerebellar degeneration, epilepsy, urinary incontinence, movement disorders, chronic pain, migraine and chronic tinnitus, etc. Several reports showed the therapeutic effects of rTMS as a treatment of depression and Parkinson disease (PD), whereas others found no significant effects. It is by now not yet fully understood whether rTMS has a therapeutic effect on those diseases. The controversy arises from the differences of the stimulation parameters and evaluation methods of the effects in those studies. The Japanese multi-center, double blinded, sham stimulation controlled trial in 85 patients with PD showed an efficacy in both the rTMS-treated and sham stimulated patients. This result does not prove the efficacy of the rTMS in PD; on the other hand, it does not rule out the efficacy. Possible mechanism of favorable effects of rTMS is related to increasing the release of dopamine in the mesolimbic and mesostriatal system. The other Japanese multi-center, double blinded, sham stimulation controlled trial in 99 patients with spinocerebellar degeneration revealed significant therapeutic effects of rTMS in 51 patients with SCA6. We studied the effects of rTMS on seizure susceptibility in rats which prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. This finding suggests the possibility of therapeutic use of rTMS in epilepsy. Further studies should be performed aiming to reveal the optimal stimulation parameters, and are necessary to reveal the therapeutic role of the rTMS in neurological and psychiatric diseases.

Cyborg psychiatry to ensure agency and autonomy in mental disorders. A proposal for neuromodulation therapeutics

PubMed Central

Micoulaud-Franchi, Jean-Arthur; Fond, Guillaume; Dumas, Guillaume

2013-01-01

Neuromodulation therapeutics—as repeated Transcranial Magnetic Stimulation (rTMS) and neurofeedback—are valuable tools for psychiatry. Nevertheless, they currently face some limitations: rTMS has confounding effects on neural activation patterns, and neurofeedback fails to change neural dynamics in some cases. Here we propose how coupling rTMS and neurofeedback can tackle both issues by adapting neural activations during rTMS and actively guiding individuals during neurofeedback. An algorithmic challenge then consists in designing the proper recording, processing, feedback, and control of unwanted effects. But this new neuromodulation technique also poses an ethical challenge: ensuring treatment occurs within a biopsychosocial model of medicine, while considering both the interaction between the patients and the psychiatrist, and the maintenance of individuals' autonomy. Our solution is the concept of Cyborg psychiatry, which embodies the technique and includes a self-engaged interaction between patients and the neuromodulation device. PMID:24046734

Cyborg psychiatry to ensure agency and autonomy in mental disorders. A proposal for neuromodulation therapeutics.

PubMed

Micoulaud-Franchi, Jean-Arthur; Fond, Guillaume; Dumas, Guillaume

2013-01-01

Neuromodulation therapeutics-as repeated Transcranial Magnetic Stimulation (rTMS) and neurofeedback-are valuable tools for psychiatry. Nevertheless, they currently face some limitations: rTMS has confounding effects on neural activation patterns, and neurofeedback fails to change neural dynamics in some cases. Here we propose how coupling rTMS and neurofeedback can tackle both issues by adapting neural activations during rTMS and actively guiding individuals during neurofeedback. An algorithmic challenge then consists in designing the proper recording, processing, feedback, and control of unwanted effects. But this new neuromodulation technique also poses an ethical challenge: ensuring treatment occurs within a biopsychosocial model of medicine, while considering both the interaction between the patients and the psychiatrist, and the maintenance of individuals' autonomy. Our solution is the concept of Cyborg psychiatry, which embodies the technique and includes a self-engaged interaction between patients and the neuromodulation device.

Assessment and modulation of neuroplasticity in rehabilitation with transcranial magnetic stimulation

PubMed Central

Bashir, Shahid; Mizrahi, Ilan; Weaver, Kayleen; Fregni, Felipe; Pascual-Leone, Alvaro

2013-01-01

Despite intensive efforts towards the improvement of outcomes after acquired brain injury functional recovery is often limited. One reasons is the challenge in assessing and guiding plasticity after brain injury. In this context, Transcranial Magnetic Stimulation (TMS) - a noninvasive tool of brain stimulation - could play a major role. TMS has shown to be a reliable tool to measure plastic changes in the motor cortex associated with interventions in the motor system; such as motor training and motor cortex stimulation. In addition, as illustrated by the experience in promoting recovery from stroke, TMS a promising therapeutic tool to minimize motor, speech, cognitive, and mood deficits. In this review, we will focus on stroke to discuss how TMS can provide insights into the mechanisms of neurological recovery, and can be used for measurement and modulation of plasticity after an acquired brain insult. PMID:21172687

Determination of stimulation focality in heterogeneous head models during transcranial magnetic stimulation (TMS)

NASA Astrophysics Data System (ADS)

Lee, Erik; Hadimani, Ravi; Jiles, David

2015-03-01

Transcranial Magnetic Stimulation (TMS) is an increasingly popular tool used by both the scientific and medical community to understand and treat the brain. TMS has the potential to help people with a wide range of diseases such as Parkinson's, Alzheimer's, and PTSD, while currently being used to treat people with chronic, drug-resistant depression. Through computer simulations, we are able to see the electric field that TMS induces in anatomical human models, but there is no measure to quantify this electric field in a way that relates to a specific patient undergoing TMS therapy. We propose a way to quantify the focality of the induced electric field in a heterogeneous head model during TMS by relating the surface area of the brain being stimulated to the total volume of the brain being stimulated. This figure would be obtained by conducting finite element analysis (FEA) simulations of TMS therapy on a patient specific head model. Using this figure to assist in TMS therapy will allow clinicians and researchers to more accurately stimulate the desired region of a patient's brain and be more equipped to do comparative studies on the effects of TMS across different patients. This work was funded by the Carver Charitable Trust.

Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura.

PubMed

Conte, Antonella; Barbanti, Piero; Frasca, Vittorio; Iacovelli, Elisa; Gabriele, Maria; Giacomelli, Elena; Aurilia, Cinzia; Pichiorri, Floriana; Gilio, Francesca; Inghilleri, Maurizio

2010-01-01

To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5Hz-rTMS in the three groups tested. The 5Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura. Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Examining frontotemporal connectivity and rTMS in healthy controls: implications for auditory hallucinations in schizophrenia.

PubMed

Gromann, Paula M; Tracy, Derek K; Giampietro, Vincent; Brammer, Michael J; Krabbendam, Lydia; Shergill, Sukhwinder S

2012-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been shown to have clinically beneficial effects in altering the perception of auditory hallucinations (AH) in patients with schizophrenia. However, the mode of action is not clear. Recent neuroimaging findings indicate that rTMS has the potential to induce not only local effects but also changes in remote, functionally connected brain regions. Frontotemporal dysconnectivity has been proposed as a mechanism leading to psychotic symptoms in schizophrenia. The current study examines functional connectivity between temporal and frontal brain regions after rTMS and the implications for AH in schizophrenia. A connectivity analysis was conducted on the fMRI data of 11 healthy controls receiving rTMS, compared with 11 matched subjects receiving sham TMS, to the temporoparietal junction, before engaging in a task associated with robust frontotemporal activation. Compared to the control group, the rTMS group showed an altered frontotemporal connectivity with stronger connectivity between the right temporoparietal cortex and the dorsolateral prefrontal cortex and the angular gyrus. This finding provides preliminary evidence for the hypothesis that normalizing the functional connectivity between the temporoparietal and frontal brain regions may underlie the therapeutic effect of rTMS on AH in schizophrenia.

Behavioral and TMS Markers of Action Observation Might Reflect Distinct Neuronal Processes.

PubMed

Hétu, Sébastien; Taschereau-Dumouchel, Vincent; Meziane, Hadj Boumediene; Jackson, Philip L; Mercier, Catherine

2016-01-01

Transcranial magnetic stimulation (TMS) studies have shown that observing an action induces muscle-specific changes in corticospinal excitability. From a signal detection theory standpoint, this pattern can be related to sensitivity, which here would measure the capacity to distinguish between two action observation conditions. In parallel to these TMS studies, action observation has also been linked to behavioral effects such as motor priming and interference. It has been hypothesized that behavioral markers of action observation could be related to TMS markers and thus represent a potentially cost-effective mean of assessing the functioning of the action-perception system. However, very few studies have looked at possible relationships between these two measures. The aim of this study was to investigate if individual differences in sensitivity to action observation could be related to the behavioral motor priming and interference effects produced by action observation. To this end, 14 healthy participants observed index and little finger movements during a TMS task and a stimulus-response compatibility task. Index muscle displayed sensitivity to action observation, and action observation resulted in significant motor priming+interference, while no significant effect was observed for the little finger in both task. Nevertheless, our results indicate that the sensitivity measured in TMS was not related to the behavioral changes measured in the stimulus-response compatibility task. Contrary to a widespread assumption, the current results indicate that individual differences in physiological and behavioral markers of action observation may be unrelated. This could have important impacts on the potential use of behavioral markers in place of more costly physiological markers of action observation in clinical settings.

Transcranial magnetic stimulation as an investigative tool for motor dysfunction and recovery in stroke: an overview for neurorehabilitation clinicians

PubMed Central

Cortes, Mar; Black-Schaffer, Randie M; Edwards, Dylan J

2012-01-01

Rationale An improved understanding of motor dysfunction and recovery after stroke has important clinical implications that may lead to the design of more effective rehabilitation strategies for patients with hemiparesis. Scope Transcranial magnetic stimulation (TMS) is a safe and painless tool that has been used in conjunction with other existing diagnostic tools to investigate motor pathophysiology in stroke patients. Since TMS emerged over two decades ago, its application in clinical and basic neuroscience has expanded worldwide. TMS can quantify the corticomotor excitability properties of clinically affected and unaffected muscles, and probe local cortical networks, as well as remote but functionally related areas. This provides novel insight into the physiology of neural circuits underlying motor dysfunction, and brain reorganization during the motor recovery process. This important tool needs to be used with caution by clinical investigators, its limitations need to be understood and the results should be interpreted along with clinical evaluation in this patient population. Summary In this review, we provide an overview of the rationale, implementation and limitations of TMS to study stroke motor physiology. This knowledge may be useful to guide future rehabilitation treatments by assessing and promoting functional plasticity. PMID:22624621

Low-frequency repetitive transcranial magnetic stimulation (rTMS) affects event-related potential measures of novelty processing in autism.

PubMed

Sokhadze, Estate; Baruth, Joshua; Tasman, Allan; Mansoor, Mehreen; Ramaswamy, Rajesh; Sears, Lonnie; Mathai, Grace; El-Baz, Ayman; Casanova, Manuel F

2010-06-01

In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37-51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.

Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia: clinical and physiological effects

PubMed Central

Kimberley, Teresa Jacobson; Borich, Michael R.; Arora, Sanjeev; Siebner, Hartwig R.

2016-01-01

Purpose The ability of low-frequency repetitive transcranial magnetic stimulation (rTMS) to enhance intracortical inhibition has motivated its use as a potential therapeutic intervention in focal hand dystonia (FHD). In this preliminary investigation, we assessed the physiologic and behavioral effects of multiple sessions of rTMS in FHD. Methods 12 patients with FHD underwent five daily-sessions of 1Hz rTMS to contralateral dorsal premotor cortex (dPMC). Patients held a pencil and made movements that did not elicit dystonic symptoms during rTMS. We hypothesized that an active but non-dystonic motor state would increase beneficial effects of rTMS. Five additional patients received sham-rTMS protocol. The area under curve (AUC) of the motor evoked potentials and the cortical silent period (CSP) were measured to assess changes in corticospinal excitability and intracortical inhibition, respectively. Behavioral measures included pen force and velocity during handwriting and subjective report. Results Multiple-session rTMS strengthened intracortical inhibition causing a prolongation of CSP after 3 days of intervention and pen force was reduced at day 1 and 5, leaving other measures unchanged. 68% of patients self-reported as ‘responders’ at day 5, and 58% at follow-up. Age predicted responders. Conclusions A strong therapeutic potential of this rTMS paradigm in FHD was not supported but findings warrant further investigation. PMID:23340117

Effects of 20 Hz Repetitive Transcranial Magnetic Stimulation on Disorders of Consciousness: A Resting-State Electroencephalography Study.

PubMed

He, Fangping; Wu, Min; Meng, Fanxia; Hu, Yangfan; Gao, Jian; Chen, Zhongqin; Bao, Wangxiao; Liu, Kehong; Luo, Benyan; Pan, Gang

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an experimental approach for the treatment of disorders of consciousness (DOC). To date, there has been little research into the use of rTMS in DOC and the therapeutic effects have been variously documented. This study aimed to examine the effects of 20 Hz rTMS on the electroencephalography (EEG) reactivity and clinical response in patients with DOC and to explore the neuromodulatory effects of high-frequency rTMS. In this randomized, sham-controlled, crossover study, real or sham 20 Hz rTMS was applied to the left primary motor cortex (M1) of patients with DOC for 5 consecutive days. Evaluations were blindly performed at the baseline (T0), immediately after the end of the 5 days of treatment (T1) and 1 week after the treatment (T2) using the JFK coma recovery scale-revised (CRS-R) and resting-state EEG. Only one patient, with a history of 2 months of traumatic brain injury, showed long-lasting (T1, T2) behavioral and neurophysiological modifications after the real rTMS stimulation. The 5 remaining patients presented brain reactivity localized at several electrodes, and the EEG modification was not significant. rTMS stimulation may improve awareness and arousal of DOC. Additionally, EEG represents a potential biomarker for the therapeutic efficacy of rTMS. This trial is registered with (NCT03385278).

Concurrent application of TMS and near-infrared optical imaging: methodological considerations and potential artifacts

PubMed Central

Parks, Nathan A.

2013-01-01

The simultaneous application of transcranial magnetic stimulation (TMS) with non-invasive neuroimaging provides a powerful method for investigating functional connectivity in the human brain and the causal relationships between areas in distributed brain networks. TMS has been combined with numerous neuroimaging techniques including, electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET). Recent work has also demonstrated the feasibility and utility of combining TMS with non-invasive near-infrared optical imaging techniques, functional near-infrared spectroscopy (fNIRS) and the event-related optical signal (EROS). Simultaneous TMS and optical imaging affords a number of advantages over other neuroimaging methods but also involves a unique set of methodological challenges and considerations. This paper describes the methodology of concurrently performing optical imaging during the administration of TMS, focusing on experimental design, potential artifacts, and approaches to controlling for these artifacts. PMID:24065911

Acute Frontal Lobe Dysfunction Following Prefrontal Low-Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Treatment-Resistant Depression

PubMed Central

Carle, Guilhem; Touat, Mehdi; Bruno, Nicolas; Galanaud, Damien; Peretti, Charles-Siegfried; Valero-Cabré, Antoni; Levy, Richard; Azuar, Carole

2017-01-01

The potential of repetitive transcranial magnetic stimulation (rTMS) to treat numerous neurological and psychiatric disorders has been thoroughly studied for the last two decades. Here, we report for the first time, the case of a 65-year-old woman suffering from treatment-resistant depression who developed an acute frontal lobe syndrome following eight sessions of low-frequency rTMS (LF-rTMS) to the right dorsolateral prefrontal cortex while also treated with sertraline and mianserin. The pathophysiological mechanisms underlying such an unexpected acute frontal lobe dysfunction are discussed in relation to the therapeutic use of LF-rTMS in combination with pharmacotherapy in depressed patients. PMID:28611694

No influence of one right-sided prefrontal HF-rTMS session on alcohol craving in recently detoxified alcohol-dependent patients: results of a naturalistic study.

PubMed

Herremans, S C; Baeken, C; Vanderbruggen, N; Vanderhasselt, M A; Zeeuws, D; Santermans, L; De Raedt, R

2012-01-01

Prior research in substance dependence has suggested potential anti-craving effects of repetitive transcranial magnetic stimulation (rTMS) when applied to the dorsolateral prefrontal cortex (DLPFC). However, no single sham-controlled session studies applied to the right DLPFC have been carried-out in recently detoxified alcohol-dependent patients. Furthermore, no studies examined the effect of a single HF-rTMS session on craving in these patients' natural habitat. To further investigate the effect of high-frequency (HF)-rTMS of the right DLPFC on alcohol craving, we performed a prospective, single-blind, sham-controlled study involving 36 hospitalized patients with alcohol dependence syndrome. After successful detoxification, patients were allocated receiving one active or one sham HF-rTMS session. The obsessive-compulsive drinking scale (OCDS) was administered to evaluate the extent of craving just before and after the HF-rTMS session (on Friday), on Saturday and Sunday during the weekend at home, and on Monday when the patient returned to the hospital. One single blind sham-controlled HF-rTMS session applied to the right DLPFC did not result in changes in craving (neither immediately after the stimulation session, nor in patients' natural environment during the weekend). One HF-rTMS stimulation session applied to the right DLPFC had no significant effects on alcohol craving in alcohol dependent patients. One such session could have been too short to alter alcohol craving in a sample of alcohol dependent patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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:26431529

Probing the frontostriatal loops involved in executive and limbic processing via interleaved TMS and functional MRI at two prefrontal locations: a pilot study.

PubMed

Hanlon, Colleen A; Canterberry, Melanie; Taylor, Joseph J; DeVries, William; Li, Xingbao; Brown, Truman R; George, Mark S

2013-01-01

The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by Alexander et al. (1986) the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial cortical-subcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment. Seventeen healthy individuals received interleaved TMS-BOLD imaging with the coil positioned over the dorsolateral (EEG: F3) and ventromedial PFC (EEG: FP1). BOLD signal change was calculated in the areas directly stimulated by the coil and in subcortical regions with afferent and efferent connectivity to the TMS target areas. Additionally, five individuals were tested on two occasions to determine test-retest reliability. Region of interest analysis revealed that TMS at both prefrontal sites led to significant BOLD signal increases in the cortex under the coil, in the striatum, and the thalamus, but not in the visual cortex (negative control region). There was a significantly larger BOLD signal change in the caudate following medial PFC TMS, relative to lateral TMS. The hippocampus in contrast was significantly more activated by lateral TMS. Post-hoc voxel-based analysis revealed that within the caudate the location of peak activity was in the ventral caudate following medial TMS and the dorsal caudate following lateral TMS. Test-retest reliability data revealed consistent BOLD responses to TMS within each individual but a large variation between individuals. These data demonstrate that, through an optimized TMS/BOLD sequence over two unique prefrontal targets, it is possible to selectively interrogate the patency of these established cortical-subcortical networks in healthy individuals, and potentially patient populations.

Transcranial magnetic stimulation in myoclonus of different aetiologies.

PubMed

Nardone, Raffaele; Versace, Viviana; Höller, Yvonne; Sebastianelli, Luca; Brigo, Francesco; Lochner, Piergiorgio; Golaszewski, Stefan; Saltuari, Leopold; Trinka, Eugen

2018-05-24

Transcranial magnetic stimulation (TMS) may represent a valuable tool for investigating important neurophysiological and pathophysiological aspects of myoclonus. Moreover, repetitive TMS (rTMS) can influence neural activity. In this review we performed a systematic search of all studies using TMS in order to explore cortical excitability/plasticity and rTMS for the treatment of myoclonus due to different aetiologies. We identified and reviewed 40 articles matching the inclusion criteria; 415 patients were included in these studies. The reviewed TMS studies have detected abnormalities in motor cortex excitability and sensorimotor plasticity. The most consistent finding is a decrease in intracortical inhibition. Short-interval intracortical inhibition (SICI) is reduced in myoclonic epilepsies. Unlike the juvenile and the benign myoclonus epilepsy, long-interval intracortical inhibition, interhemispheric inhibition and sensorimotor integration were altered in patients with progressive myoclonic epilepsies. In patients with myoclonus-dystonia the results are partly conflicting. Cortical membrane excitability was impaired while parameters assessing cortical synaptic activity were normal in DYT11 gene carriers. In other studies normal SICI suggests that the GABAergic cortical circuits are largely intact and that the mechanisms of myoclonus-dystonia are different from those for cortical myoclonus and other dystonic disorders. In conclusion, different TMS study protocols have provided new insights into sensorimotor plasticity and cortical excitability of the different forms of myoclonus, and have shed some light on the pathophysiology of this movement disorder. Well-defined motor cortical excitability patterns can be identified in the different disorders characterized by myoclonus, even if preliminary findings should be confirmed in future studies in larger cohorts of patients. Repetitive TMS might have therapeutic potential at least in some patients with myoclonus, similar to that reported in other neurological and psychiatric disorders. Copyright © 2018. Published by Elsevier Inc.

Is the human mirror neuron system plastic? Evidence from a transcranial magnetic stimulation study.

PubMed

Mehta, Urvakhsh Meherwan; Waghmare, Avinash V; Thirthalli, Jagadisha; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

2015-10-01

Virtual lesions in the mirror neuron network using inhibitory low-frequency (1Hz) transcranial magnetic stimulation (TMS) have been employed to understand its spatio-functional properties. However, no studies have examined the influence of neuro-enhancement by using excitatory high-frequency (20Hz) repetitive transcranial magnetic stimulation (HF-rTMS) on these networks. We used three forms of TMS stimulation (HF-rTMS, single and paired pulse) to investigate whether the mirror neuron system facilitates the motor system during goal-directed action observation relative to inanimate motion (motor resonance), a marker of putative mirror neuron activity. 31 healthy individuals were randomized to receive single-sessions of true or sham HF-rTMS delivered to the left inferior frontal gyrus - a component of the human mirror system. Motor resonance was assessed before and after HF-rTMS using three TMS cortical reactivity paradigms: (a) 120% of resting motor threshold (RMT), (b) stimulus intensity set to evoke motor evoked potential of 1-millivolt amplitude (SI1mV) and (c) a short latency paired pulse paradigm. Two-way RMANOVA showed a significant group (true versus sham) X occasion (pre- and post-HF-rTMS motor resonance) interaction effect for SI1mV [F(df)=6.26 (1, 29), p=0.018] and 120% RMT stimuli [F(df)=7.01 (1, 29), p=0.013] indicating greater enhancement of motor resonance in the true HF-rTMS group than the sham-group. This suggests that HF-rTMS could adaptively modulate properties of the mirror neuron system. This neuro-enhancement effect is a preliminary step that can open translational avenues for novel brain stimulation therapeutics targeting social-cognition deficits in schizophrenia and autism. Copyright © 2015 Elsevier B.V. All rights reserved.

Modulatory effects of high-frequency repetitive transcranial magnetic stimulation on the ipsilateral silent period.

PubMed

Cincotta, M; Giovannelli, F; Borgheresi, A; Balestrieri, F; Zaccara, G; Inghilleri, M; Berardelli, A

2006-06-01

In healthy subjects, suprathreshold repetitive transcranial magnetic stimulation (rTMS) at frequencies >2 Hz prolongs the cortical silent period (CSP) over the course of the train. This progressive lengthening probably reflects temporal summation of the inhibitory interneurons in the stimulated primary motor cortex (M1). In this study, we tested whether high-frequency rTMS also modulates the ipsilateral silent period (ISP). In nine normal subjects, suprathreshold 10-pulse rTMS trains were delivered to the right M1 at frequencies of 3, 5, and 10 Hz during maximal isometric contraction of both first dorsal interosseous muscles. At 10 Hz, the second pulse of the train increased the area of the ISP; the other stimuli did not increase it further. During rTMS at 3 and 5 Hz, the ISP remained significantly unchanged. Control experiments showed that 10-Hz rTMS delivered at subthreshold intensity also increased the ISP. rTMS over the hand motor area did not facilitate ISPs in the biceps muscles. Finally, rTMS-induced ISP facilitation did not outlast the 10-Hz rTMS train. These findings suggest that rTMS at a frequency of 10 Hz potentiates the interhemispheric inhibitory mechanisms responsible for the ISP, partly through temporal summation. The distinct changes in the ISP and CSP suggest that rTMS facilitates intrahemispheric and interhemispheric inhibitory phenomena through separate neural mechanisms. The ISP facilitation induced by high-frequency rTMS is a novel, promising tool to investigate pathophysiological abnormal interhemispheric inhibitory transfer in various neurological diseases.

Transcranial magnetic stimulation for tinnitus: using the Tinnitus Functional Index to predict benefit in a randomized controlled trial.

PubMed

Theodoroff, Sarah M; Griest, Susan E; Folmer, Robert L

2017-02-09

Identifying characteristics associated with transcranial magnetic stimulation (TMS) benefit would offer insight as to why some individuals experience tinnitus relief following TMS treatment, whereas others do not. The purpose of this study was to use the Tinnitus Functional Index (TFI) and its subscales to identify specific factors associated with TMS treatment responsiveness. Individuals with bothersome tinnitus underwent 2000 pulses of 1-Hz TMS for 10 consecutive business days. The primary outcome measure was the TFI which yields a total score and eight individual subscale scores. Analyses were performed on baseline data from the active arm (n = 35) of a prospective, double-blind, randomized placebo-controlled clinical trial of TMS for tinnitus. Baseline total TFI score and three of the eight TFI subscales were useful in differentiating between responders and nonresponders to TMS intervention for tinnitus. These findings are not definitive, but suggest potential factors that contribute to perceived benefit following TMS. Overall, the main factor associated with TMS benefit was a higher tinnitus severity score for responders at baseline. The TFI subscales helped to clarify the factors that contributed to a higher severity score at baseline. Large-scale prospective research using systematic approaches is needed to identify and describe additional factors associated with tinnitus benefit following TMS. ClinicalTrials.gov, ID: NCT01104207 . Registered on 13 April 2010.

Translational Neuromodulation: Approximating Human Transcranial Magnetic Stimulation Protocols In Rats

PubMed Central

Vahabzadeh-Hagh, Andrew M.; Muller, Paul A.; Gersner, Roman; Zangen, Abraham; Rotenberg, Alexander

2015-01-01

Objective Transcranial magnetic stimulation (TMS) is a well-established clinical protocol with numerous potential therapeutic and diagnostic applications. Yet, much work remains in the elucidation of TMS mechanisms, optimization of protocols, and in development of novel therapeutic applications. As with many technologies, the key to these issues lies in the proper experimentation and translation of TMS methods to animal models, among which rat models have proven popular. A significant increase in the number of rat TMS publications has necessitated analysis of their relevance to human work. We therefore review the essential principles necessary for the approximation of human TMS protocols in rats as well as specific methods that addressed these issues in published studies. Materials and Methods We performed an English language literature search combined with our own experience and data. We address issues that we see as important in the translation of human TMS methods to rat models and provide a summary of key accomplishments in these areas. Results An extensive literature review illustrated the growth of rodent TMS studies in recent years. Current advances in the translation of single, paired-pulse, and repetitive stimulation paradigms to rodent models are presented. The importance of TMS in the generation of data for preclinical trials is also highlighted. Conclusions Rat TMS has several limitations when considering parallels between animal and human stimulation. However, it has proven to be a useful tool in the field of translational brain stimulation and will likely continue to aid in the design and implementation of stimulation protocols for therapeutic and diagnostic applications. PMID:22780329

Assessment and management of human health risk from toxic metals and polycyclic aromatic hydrocarbons in urban stormwater arising from anthropogenic activities and traffic congestion.

PubMed

Ma, Yukun; Liu, An; Egodawatta, Prasanna; McGree, James; Goonetilleke, Ashantha

2017-02-01

Toxic metals (TMs) and polycyclic aromatic hydrocarbons (PAHs) in urban stormwater pose risk to human health, thereby constraining its reuse potential. Based on the hypothesis that stormwater quality is primarily influenced by anthropogenic activities and traffic congestion, the primary focus of the research study was to analyse the impacts on human health risk from TMs and PAHs in urban stormwater and thereby develop a quantitative risk assessment model. The study found that anthropogenic activities and traffic congestion exert influence on the risk posed by TMs and PAHs in stormwater from commercial and residential areas. Motor vehicle related businesses (FVS) and traffic congestion (TC) were identified as two parameters which need to be included as independent variables to improve the model. Based on the study outcomes, approaches for mitigating the risk associated with TMs and PAHs in urban stormwater are discussed. Additionally, a roadmap is presented for the assessment and management of the risk arising from these pollutants. The study outcomes are expected to contribute to reducing the human health risk associated urban stormwater pollution and thereby enhance its reuse potential. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhancement of human cognitive performance using transcranial magnetic stimulation (TMS)

PubMed Central

Luber, Bruce; Lisanby, and Sarah H.

2014-01-01

Here we review the usefulness of transcranial magnetic stimulation (TMS) in modulating cortical networks in ways that might produce performance enhancements in healthy human subjects. To date over sixty studies have reported significant improvements in speed and accuracy in a variety of tasks involving perceptual, motor, and executive processing. Two basic categories of enhancement mechanisms are suggested by this literature: direct modulation of a cortical region or network that leads to more efficient processing, and addition-by-subtraction, which is disruption of processing which competes or distracts from task performance. Potential applications of TMS cognitive enhancement, including research into cortical function, rehabilitation therapy in neurological and psychiatric illness, and accelerated skill acquisition in healthy individuals are discussed, as are methods of optimizing the magnitude and duration of TMS-induced performance enhancement, such as improvement of targeting through further integration of brain imaging with TMS. One technique, combining multiple sessions of TMS with concurrent TMS/task performance to induce Hebbian-like learning, appears to be promising for prolonging enhancement effects. While further refinements in the application of TMS to cognitive enhancement can still be made, and questions remain regarding the mechanisms underlying the observed effects, this appears to be a fruitful area of investigation that may shed light on the basic mechanisms of cognitive function and their therapeutic modulation. PMID:23770409

Deep transcranial magnetic stimulation for the treatment of auditory hallucinations: a preliminary open-label study

PubMed Central

2011-01-01

Background Schizophrenia is a chronic and disabling disease that presents with delusions and hallucinations. Auditory hallucinations are usually expressed as voices speaking to or about the patient. Previous studies have examined the effect of repetitive transcranial magnetic stimulation (TMS) over the temporoparietal cortex on auditory hallucinations in schizophrenic patients. Our aim was to explore the potential effect of deep TMS, using the H coil over the same brain region on auditory hallucinations. Patients and methods Eight schizophrenic patients with refractory auditory hallucinations were recruited, mainly from Beer Ya'akov Mental Health Institution (Tel Aviv university, Israel) ambulatory clinics, as well as from other hospitals outpatient populations. Low-frequency deep TMS was applied for 10 min (600 pulses per session) to the left temporoparietal cortex for either 10 or 20 sessions. Deep TMS was applied using Brainsway's H1 coil apparatus. Patients were evaluated using the Auditory Hallucinations Rating Scale (AHRS) as well as the Scale for the Assessment of Positive Symptoms scores (SAPS), Clinical Global Impressions (CGI) scale, and the Scale for Assessment of Negative Symptoms (SANS). Results This preliminary study demonstrated a significant improvement in AHRS score (an average reduction of 31.7% ± 32.2%) and to a lesser extent improvement in SAPS results (an average reduction of 16.5% ± 20.3%). Conclusions In this study, we have demonstrated the potential of deep TMS treatment over the temporoparietal cortex as an add-on treatment for chronic auditory hallucinations in schizophrenic patients. Larger samples in a double-blind sham-controlled design are now being preformed to evaluate the effectiveness of deep TMS treatment for auditory hallucinations. Trial registration This trial is registered with clinicaltrials.gov (identifier: NCT00564096). PMID:21303566

Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

PubMed Central

Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

2014-01-01

Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in intact, awake monkeys (Macaca mulatta). We recorded action potentials within ~1 ms after 0.4 ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared to sham stimulation. The methodology is compatible with standard equipment in primate laboratories, allowing for easy implementation. Application of these new tools will facilitate the refinement of next generation TMS devices, experiments, and treatment protocols. PMID:24974797

Repetitive transcranial magnetic stimulator with controllable pulse parameters

NASA Astrophysics Data System (ADS)

Peterchev, Angel V.; Murphy, David L.; Lisanby, Sarah H.

2011-06-01

The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10-310 µs and positive/negative phase amplitude ratio of 1-56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation up to 82% and 57% and decreases coil heating up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications and could lead to clinical applications with potentially enhanced potency.

Repetitive transcranial magnetic stimulator with controllable pulse parameters.

PubMed

Peterchev, Angel V; Murphy, David L; Lisanby, Sarah H

2011-06-01

The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10-310 µs and positive/negative phase amplitude ratio of 1-56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation up to 82% and 57% and decreases coil heating up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications and could lead to clinical applications with potentially enhanced potency.

The Efficacy of Daily Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) for Burning Mouth Syndrome (BMS): A Randomized Controlled Single-blind Study.

PubMed

Umezaki, Yojiro; Badran, Bashar W; DeVries, William H; Moss, Jkeonye; Gonzales, Theresa; George, Mark S

2016-01-01

Burning mouth syndrome (BMS) is a burning oral sensation without any corresponding abnormal findings. In some cases, BMS is refractory to pharmacologic treatments. Repetitive transcranial magnetic stimulation (rTMS) over left prefrontal cortex induces analgesic effect in both acute and chronic pain. However, its effect for BMS has not been evaluated. The aim of this randomized, controlled, single-blind study was to assess the efficacy of prefrontal rTMS for BMS. Twenty patients with BMS were recruited and randomized to receive 30,000 pulses in total at 10 Hz TMS (n = 12) or sham TMS (n = 8). We assessed the change of BMS pain condition, functional status and mood until 2 months after the beginning of treatment. In the real group, the BMS pain intensity decreased 67%, and 75% of the patients reported >50% pain decrease on final assessment compared to baseline, without heavy side effects. There was significant pain reduction in subjects in the real group immediately after 1 week of treatment, whereas there was none in those in the sham group. Similar tendency was confirmed in change of functional status. Mood and the affective aspect of pain were not changed in this study. BMS pain was significantly improved with 2 weeks of treatment of high frequency rTMS over left DLPFC compared to sham stimulation. Further study is needed to refine and improve TMS as a potential treatment of BMS. Copyright © 2016 Elsevier Inc. All rights reserved.

The use of repetitive transcranial magnetic stimulation for modulating craving and addictive behaviours: a critical literature review of efficacy, technical and methodological considerations.

PubMed

Grall-Bronnec, M; Sauvaget, A

2014-11-01

Repetitive transcranial magnetic stimulation (rTMS) is a potential therapeutic intervention for the treatment of addiction. This critical review aims to summarise the recent developments with respect to the efficacy of rTMS for all types of addiction and related disorders (including eating disorders), and concentrates on the associated methodological and technical issues. The bibliographic search consisted of a computerised screening of the Medline and ScienceDirect databases up to December 2013. Criteria for inclusion were the target problem was an addiction, a related disorder, or craving; the intervention was performed using rTMS; and the study was a clinical trial. Of the potential 638 articles, 18 met the criteria for inclusion. Most of these (11 of the 18) supported the efficacy of rTMS, especially in the short term. In most cases, the main assessment criterion was the measurement of craving using a Visual Analogue Scale. The results are discussed with respect to the study limitations and, in particular, the many methodological and technical discrepancies that were identified. Key recommendations are provided.

Definition of DLPFC and M1 according to anatomical landmarks for navigated brain stimulation: inter-rater reliability, accuracy, and influence of gender and age.

PubMed

Mylius, V; Ayache, S S; Ahdab, R; Farhat, W H; Zouari, H G; Belke, M; Brugières, P; Wehrmann, E; Krakow, K; Timmesfeld, N; Schmidt, S; Oertel, W H; Knake, S; Lefaucheur, J P

2013-09-01

The optimization of the targeting of a defined cortical region is a challenge in the current practice of transcranial magnetic stimulation (TMS). The dorsolateral prefrontal cortex (DLPFC) and the primary motor cortex (M1) are among the most usual TMS targets, particularly in its "therapeutic" application. This study describes a practical algorithm to determine the anatomical location of the DLPFC and M1 using a three-dimensional (3D) brain reconstruction provided by a TMS-dedicated navigation system from individual magnetic resonance imaging (MRI) data. The coordinates of the right and left DLPFC and M1 were determined in 50 normal brains (100 hemispheres) by five different investigators using a standardized procedure. Inter-rater reliability was good, with 95% limits of agreement ranging between 7 and 16 mm for the different coordinates. As expressed in the Talairach space and compared with anatomical or imaging data from the literature, the coordinates of the DLPFC defined by our algorithm corresponded to the junction between BA9 and BA46, while M1 coordinates corresponded to the posterior border of hand representation. Finally, we found an influence of gender and possibly of age on some coordinates on both rostrocaudal and dorsoventral axes. Our algorithm only requires a short training and can be used to provide a reliable targeting of DLPFC and M1 between various TMS investigators. This method, based on an image-guided navigation system using individual MRI data, should be helpful to a variety of TMS studies, especially to standardize the procedure of stimulation in multicenter "therapeutic" studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Novel transcranial magnetic stimulation coil for mice

NASA Astrophysics Data System (ADS)

March, Stephen; Stark, Spencer; Crowther, Lawrence; Hadimani, Ravi; Jiles, David

2014-03-01

Transcranial magnetic stimulation (TMS) shows potential for non-invasive treatment of various neurological disorders. Significant work has been performed on the design of coils used for TMS on human subjects but few reports have been made on the design of coils for use on the brains of animals such as mice. This work is needed as TMS studies utilizing mice can allow rapid preclinical development of TMS for human disorders but the coil designs developed for use on humans are inadequate for optimal stimulation of the much smaller mouse brain. A novel TMS coil has been developed with the goal of inducing strong and focused electric fields for the stimulation of small animals such as mice. Calculations of induced electric fields were performed utilizing an MRI derived inhomogeneous model of an adult male mouse. Mechanical and thermal analysis of this new TMS helmet-coil design have also been performed at anticipated TMS operating conditions to ensure mechanical stability of the new coil and establish expected linear attraction and rotational force values. Calculated temperature increases for typical stimulation periods indicate the helmet-coil system is capable of operating within established medical standards. A prototype of the coil has been fabricated and characterization results are presented.

Clinical and electrophysiological impact of repetitive low-frequency transcranial magnetic stimulation on the sensory–motor network in patients with restless legs syndrome

PubMed Central

Cantone, Mariagiovanna; Aricò, Debora; Lanuzza, Bartolo; Cosentino, Filomena Irene Ilaria; Paci, Domenico; Papotto, Maurizio; Pennisi, Manuela; Bella, Rita; Pennisi, Giovanni; Paulus, Walter; Ferri, Raffaele

2018-01-01

Background: Based on the hyperexcitability and disinhibition observed in patients with restless legs syndrome (RLS) following transcranial magnetic stimulation (TMS), we conducted a study with low-frequency repetitive TMS (rTMS) over the primary motor (M1) and somatosensory cortical areas (S1) in patients with RLS. Methods: A total of 13 right-handed patients and 10 age-matched controls were studied using clinical scales and TMS. Measurements included resting motor threshold (rMT), motor-evoked potentials (MEPs), cortical silent period (CSP), and central motor conduction time (CMCT). A single evening session of rTMS (1 Hz, 20 trains, 50 stimuli each) was administered over the left M1, left S1, and sham stimulation over M1 in a random order. Clinical and TMS measures were repeated after each stimulation modality. Results: Baseline CSP was shorter in patients than in controls and remained shorter in patients for both motor and somatosensory stimulation. The patients reported a subjective improvement of both initiating and maintaining sleep the night after the rTMS over S1. Patients exhibited a decrease in rMT after rTMS of S1 only, although the effect was smaller than in controls. MEP latency and CMCT changed only in controls after stimulation. Sham stimulation was without effect on the observed variables. Conclusions: rTMS on S1-M1 connectivity alleviated the sensory–motor complaints of RLS patients. The TMS indexes of excitation and inhibition indicate an intracortical and corticospinal imbalance, mainly involving gamma-aminobutyric acid (GABA)ergic and glutamatergic circuitries, as well as an impairment of the short-term mechanisms of cortical plasticity. The rTMS-induced activation of the dorsal striatum with the consequent increase of dopamine release may have contributed to the clinical and neurophysiological outcome. PMID:29511386

Using a Double-Coil TMS Protocol to Assess Preparatory Inhibition Bilaterally.

PubMed

Vassiliadis, Pierre; Grandjean, Julien; Derosiere, Gerard; de Wilde, Ysaline; Quemener, Louise; Duque, Julie

2018-01-01

Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1), elicits motor-evoked potentials (MEPs) in contralateral limb muscles which are valuable indicators of corticospinal excitability (CSE) at the time of stimulation. So far, most studies have used single-coil TMS over one M1, yielding MEPs in muscles of a single limb-usually the hand. However, tracking CSE in the two hands simultaneously would be useful in many contexts. We recently showed that, in the resting state, double-coil stimulation of the two M1 with a 1 ms inter-pulse interval (double-coil 1 ms TMS) elicits MEPs in both hands that are comparable to MEPs obtained using single-coil TMS. To further evaluate this new technique, we considered the MEPs elicited by double-coil 1 ms TMS in an instructed-delay choice reaction time task where a prepared response has to be withheld until an imperative signal is displayed. Single-coil TMS studies have repetitively shown that in this type of task, the motor system is transiently inhibited during the delay period, as evident from the broad suppression of MEP amplitudes. Here, we aimed at investigating whether a comparable inhibitory effect can be observed with MEPs elicited using double-coil 1 ms TMS. To do so, we compared the amplitude as well as the coefficient of variation (CV) of MEPs produced by double-coil 1 ms or single-coil TMS during action preparation. We observed that MEPs were suppressed (smaller amplitude) and often less variable (smaller CV) during the delay period compared to baseline. Importantly, these effects were equivalent whether single-coil or double-coil 1 ms TMS was used. This suggests that double-coil 1 ms TMS is a reliable tool to assess CSE, not only when subjects are at rest, but also when they are involved in a task, opening new research horizons for scientists interested in the corticospinal correlates of human behavior.

Using a Double-Coil TMS Protocol to Assess Preparatory Inhibition Bilaterally

PubMed Central

Vassiliadis, Pierre; Grandjean, Julien; Derosiere, Gerard; de Wilde, Ysaline; Quemener, Louise; Duque, Julie

2018-01-01

Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1), elicits motor-evoked potentials (MEPs) in contralateral limb muscles which are valuable indicators of corticospinal excitability (CSE) at the time of stimulation. So far, most studies have used single-coil TMS over one M1, yielding MEPs in muscles of a single limb—usually the hand. However, tracking CSE in the two hands simultaneously would be useful in many contexts. We recently showed that, in the resting state, double-coil stimulation of the two M1 with a 1 ms inter-pulse interval (double-coil1 ms TMS) elicits MEPs in both hands that are comparable to MEPs obtained using single-coil TMS. To further evaluate this new technique, we considered the MEPs elicited by double-coil1 ms TMS in an instructed-delay choice reaction time task where a prepared response has to be withheld until an imperative signal is displayed. Single-coil TMS studies have repetitively shown that in this type of task, the motor system is transiently inhibited during the delay period, as evident from the broad suppression of MEP amplitudes. Here, we aimed at investigating whether a comparable inhibitory effect can be observed with MEPs elicited using double-coil1 ms TMS. To do so, we compared the amplitude as well as the coefficient of variation (CV) of MEPs produced by double-coil1 ms or single-coil TMS during action preparation. We observed that MEPs were suppressed (smaller amplitude) and often less variable (smaller CV) during the delay period compared to baseline. Importantly, these effects were equivalent whether single-coil or double-coil1 ms TMS was used. This suggests that double-coil1 ms TMS is a reliable tool to assess CSE, not only when subjects are at rest, but also when they are involved in a task, opening new research horizons for scientists interested in the corticospinal correlates of human behavior. PMID:29568258

Maximal Voluntary Activation of the Elbow Flexors Is under Predicted by Transcranial Magnetic Stimulation Compared to Motor Point Stimulation Prior to and Following Muscle Fatigue

PubMed Central

Cadigan, Edward W. J.; Collins, Brandon W.; Philpott, Devin T. G.; Kippenhuck, Garreth; Brenton, Mitchell; Button, Duane C.

2017-01-01

Transcranial magnetic (TMS) and motor point stimulation have been used to determine voluntary activation (VA). However, very few studies have directly compared the two stimulation techniques for assessing VA of the elbow flexors. The purpose of this study was to compare TMS and motor point stimulation for assessing VA in non-fatigued and fatigued elbow flexors. Participants performed a fatigue protocol that included twelve, 15 s isometric elbow flexor contractions. Participants completed a set of isometric elbow flexion contractions at 100, 75, 50, and 25% of maximum voluntary contraction (MVC) prior to and following fatigue contractions 3, 6, 9, and 12 and 5 and 10 min post-fatigue. Force and EMG of the bicep and triceps brachii were measured for each contraction. Force responses to TMS and motor point stimulation and EMG responses to TMS (motor evoked potentials, MEPs) and Erb's point stimulation (maximal M-waves, Mmax) were also recorded. VA was estimated using the equation: VA% = (1−SITforce/PTforce) × 100. The resting twitch was measured directly for motor point stimulation and estimated for both motor point stimulation and TMS by extrapolation of the linear regression between the superimposed twitch force and voluntary force. MVC force, potentiated twitch force and VA significantly (p < 0.05) decreased throughout the elbow flexor fatigue protocol and partially recovered 10 min post fatigue. VA was significantly (p < 0.05) underestimated when using TMS compared to motor point stimulation in non-fatigued and fatigued elbow flexors. Motor point stimulation compared to TMS superimposed twitch forces were significantly (p < 0.05) higher at 50% MVC but similar at 75 and 100% MVC. The linear relationship between TMS superimposed twitch force and voluntary force significantly (p < 0.05) decreased with fatigue. There was no change in triceps/biceps electromyography, biceps/triceps MEP amplitudes, or bicep MEP amplitudes throughout the fatigue protocol at 100% MVC. In conclusion, motor point stimulation as opposed to TMS led to a higher estimation of VA in non-fatigued and fatigued elbow flexors. The decreased linear relationship between TMS superimposed twitch force and voluntary force led to an underestimation of the estimated resting twitch force and thus, a reduced VA. PMID:28979211

Maximal Voluntary Activation of the Elbow Flexors Is under Predicted by Transcranial Magnetic Stimulation Compared to Motor Point Stimulation Prior to and Following Muscle Fatigue.

PubMed

Cadigan, Edward W J; Collins, Brandon W; Philpott, Devin T G; Kippenhuck, Garreth; Brenton, Mitchell; Button, Duane C

2017-01-01

Transcranial magnetic (TMS) and motor point stimulation have been used to determine voluntary activation (VA). However, very few studies have directly compared the two stimulation techniques for assessing VA of the elbow flexors. The purpose of this study was to compare TMS and motor point stimulation for assessing VA in non-fatigued and fatigued elbow flexors. Participants performed a fatigue protocol that included twelve, 15 s isometric elbow flexor contractions. Participants completed a set of isometric elbow flexion contractions at 100, 75, 50, and 25% of maximum voluntary contraction (MVC) prior to and following fatigue contractions 3, 6, 9, and 12 and 5 and 10 min post-fatigue. Force and EMG of the bicep and triceps brachii were measured for each contraction. Force responses to TMS and motor point stimulation and EMG responses to TMS (motor evoked potentials, MEPs) and Erb's point stimulation (maximal M-waves, M max ) were also recorded. VA was estimated using the equation: VA% = (1- SITforce / PTforce ) × 100. The resting twitch was measured directly for motor point stimulation and estimated for both motor point stimulation and TMS by extrapolation of the linear regression between the superimposed twitch force and voluntary force. MVC force, potentiated twitch force and VA significantly ( p < 0.05) decreased throughout the elbow flexor fatigue protocol and partially recovered 10 min post fatigue. VA was significantly ( p < 0.05) underestimated when using TMS compared to motor point stimulation in non-fatigued and fatigued elbow flexors. Motor point stimulation compared to TMS superimposed twitch forces were significantly ( p < 0.05) higher at 50% MVC but similar at 75 and 100% MVC. The linear relationship between TMS superimposed twitch force and voluntary force significantly ( p < 0.05) decreased with fatigue. There was no change in triceps/biceps electromyography, biceps/triceps MEP amplitudes, or bicep MEP amplitudes throughout the fatigue protocol at 100% MVC. In conclusion, motor point stimulation as opposed to TMS led to a higher estimation of VA in non-fatigued and fatigued elbow flexors. The decreased linear relationship between TMS superimposed twitch force and voluntary force led to an underestimation of the estimated resting twitch force and thus, a reduced VA.

Discovery and Annotation of Plant Endogenous Target Mimicry Sequences from Public Transcriptome Libraries: A Case Study of Prunus persica.

PubMed

Karakülah, Gökhan

2017-06-28

Novel transcript discovery through RNA sequencing has substantially improved our understanding of the transcriptome dynamics of biological systems. Endogenous target mimicry (eTM) transcripts, a novel class of regulatory molecules, bind to their target microRNAs (miRNAs) by base pairing and block their biological activity. The objective of this study was to provide a computational analysis framework for the prediction of putative eTM sequences in plants, and as an example, to discover previously un-annotated eTMs in Prunus persica (peach) transcriptome. Therefore, two public peach transcriptome libraries downloaded from Sequence Read Archive (SRA) and a previously published set of long non-coding RNAs (lncRNAs) were investigated with multi-step analysis pipeline, and 44 putative eTMs were found. Additionally, an eTM-miRNA-mRNA regulatory network module associated with peach fruit organ development was built via integration of the miRNA target information and predicted eTM-miRNA interactions. My findings suggest that one of the most widely expressed miRNA families among diverse plant species, miR156, might be potentially sponged by seven putative eTMs. Besides, the study indicates eTMs potentially play roles in the regulation of development processes in peach fruit via targeting specific miRNAs. In conclusion, by following the step-by step instructions provided in this study, novel eTMs can be identified and annotated effectively in public plant transcriptome libraries.

Evidence for distinct human auditory cortex regions for sound location versus identity processing

PubMed Central

Ahveninen, Jyrki; Huang, Samantha; Nummenmaa, Aapo; Belliveau, John W.; Hung, An-Yi; Jääskeläinen, Iiro P.; Rauschecker, Josef P.; Rossi, Stephanie; Tiitinen, Hannu; Raij, Tommi

2014-01-01

Neurophysiological animal models suggest that anterior auditory cortex (AC) areas process sound-identity information, whereas posterior ACs specialize in sound location processing. In humans, inconsistent neuroimaging results and insufficient causal evidence have challenged the existence of such parallel AC organization. Here we transiently inhibit bilateral anterior or posterior AC areas using MRI-guided paired-pulse transcranial magnetic stimulation (TMS) while subjects listen to Reference/Probe sound pairs and perform either sound location or identity discrimination tasks. The targeting of TMS pulses, delivered 55–145 ms after Probes, is confirmed with individual-level cortical electric-field estimates. Our data show that TMS to posterior AC regions delays reaction times (RT) significantly more during sound location than identity discrimination, whereas TMS to anterior AC regions delays RTs significantly more during sound identity than location discrimination. This double dissociation provides direct causal support for parallel processing of sound identity features in anterior AC and sound location in posterior AC. PMID:24121634

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

PubMed

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 anesthetic and in interpreting results during prolonged TMS recording.

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

PubMed Central

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 anesthetic and in interpreting results during prolonged TMS recording. PMID:27766073

[Repetitive transcranial magnetic stimulation: A potential therapy for cognitive disorders?

PubMed

Nouhaud, C; Sherrard, R M; Belmin, J

2017-03-01

Considering the limited effectiveness of drugs treatments in cognitive disorders, the emergence of noninvasive techniques to modify brain function is very interesting. Among these techniques, repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability and have potential therapeutic effects on cognition and behaviour. These effects are due to physiological modifications in the stimulated cortical tissue and their associated circuits, which depend on the parameters of stimulation. The objective of this article is to specify current knowledge and efficacy of rTMS in cognitive disorders. Previous studies found very encouraging results with significant improvement of higher brain functions. Nevertheless, these few studies have limits: a few patients were enrolled, the lack of control of the mechanisms of action by brain imaging, insufficiently formalized technique and variability of cognitive tests. It is therefore necessary to perform more studies, which identify statistical significant improvement and to specify underlying mechanisms of action and the parameters of use of the rTMS to offer rTMS as a routine therapy for cognitive dysfunction. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Can repetitive transcranial magnetic stimulation increase muscle strength in functional neurological paresis? A proof-of-principle study.

PubMed

Broersma, M; Koops, E A; Vroomen, P C; Van der Hoeven, J H; Aleman, A; Leenders, K L; Maurits, N M; van Beilen, M

2015-05-01

Therapeutic options are limited in functional neurological paresis disorder. Earlier intervention studies did not control for a placebo effect, hampering assessment of effectivity. A proof-of-principle investigation was conducted into the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS), using a single-blind two-period placebo-controlled cross-over design. Eleven patients received active 15 Hz rTMS over the contralateral motor cortex (hand area), in two periods of 5 days, for 30 min once a day at 80% of resting motor threshold, with a train length of 2 s and an intertrain interval of 4 s. Eight of these eleven patients were also included in the placebo treatment condition. Primary outcome measure was change in muscle strength as measured by dynamometry after treatment. Secondary outcome measure was the subjective change in muscle strength after treatment. In patients who received both treatments, active rTMS induced a significantly larger median increase in objectively measured muscle strength (24%) compared to placebo rTMS (6%; P < 0.04). Subjective ratings showed no difference due to treatment, i.e. patients did not perceive these objectively measured motor improvements (P = 0.40). Our findings suggest that rTMS by itself can potentially improve muscle weakness in functional neurological paresis disorder. Whereas patients' muscle strength increased as measured with dynamometry, patients did not report increased functioning of the affected hand, subjectively. The results may indicate that decreased muscle strength is not the core symptom and that rTMS should be added to behavioral approaches in functional neurological paresis. © 2015 EAN.

Neuroimaging Mechanisms of Therapeutic Transcranial Magnetic Stimulation for Major Depressive Disorder.

PubMed

Philip, Noah S; Barredo, Jennifer; Aiken, Emily; Carpenter, Linda L

2018-03-01

Research into therapeutic transcranial magnetic stimulation (TMS) for major depression has dramatically increased in the last decade. Understanding the mechanism of action of TMS is crucial to improve efficacy and develop the next generation of therapeutic stimulation. Early imaging research provided initial data supportive of widely held assumptions about hypothesized inhibitory or excitatory consequences of stimulation. Early work also indicated that while TMS modulated brain activity under the stimulation site, effects at deeper regions, in particular, the subgenual anterior cingulate cortex, were associated with clinical improvement. Concordant with earlier findings, functional connectivity studies also demonstrated that clinical improvements were related to changes distal, rather than proximal, to the site of stimulation. Moreover, recent work suggests that TMS modulates and potentially normalizes functional relationships between neural networks. An important observation that emerged from this review is that similar patterns of connectivity changes are observed across studies regardless of TMS parameters. Though promising, we stress that these imaging findings must be evaluated cautiously given the widespread reliance on modest sample sizes and little implementation of statistical validation. Additional limitations included use of imaging before and after a course of TMS, which provided little insight into changes that might occur during the weeks of stimulation. Furthermore, as studies to date have focused on depression, it is unclear whether our observations were related to mechanisms of action of TMS for depression or represented broader patterns of functional brain changes associated with clinical improvement. Published by Elsevier Inc.

Navigated transcranial magnetic stimulation for glioma removal: prognostic value in motor function recovery from postsurgical neurological deficits.

PubMed

Takakura, Tomokazu; Muragaki, Yoshihiro; Tamura, Manabu; Maruyama, Takashi; Nitta, Masayuki; Niki, Chiharu; Kawamata, Takakazu

2017-10-01

OBJECTIVE The aim of the present study was to evaluate the usefulness of navigated transcranial magnetic stimulation (nTMS) as a prognostic predictor for upper-extremity motor functional recovery from postsurgical neurological deficits. METHODS Preoperative and postoperative nTMS studies were prospectively applied in 14 patients (mean age 39 ± 12 years) who had intraparenchymal brain neoplasms located within or adjacent to the motor eloquent area in the cerebral hemisphere. Mapping by nTMS was done 3 times, i.e., before surgery, and 1 week and 3 weeks after surgery. To assess the response induced by nTMS, motor evoked potential (nTMS-MEP) was recorded using a surface electromyography electrode attached to the abductor pollicis brevis (APB). The cortical locations that elicited the largest electromyography response by nTMS were defined as hotspots. Hotspots for APB were confirmed as positive responsive sites by direct electrical stimulation (DES) during awake craniotomy. The distances between hotspots and lesions (D HS-L ) were measured. Postoperative neurological deficits were assessed by manual muscle test and dynamometer. To validate the prognostic value of nTMS in recovery from upper-extremity paresis, the following were investigated: 1) the correlation between D HS-L and the serial grip strength change, and 2) the correlation between positive nTMS-MEP at 1 week after surgery and the serial grip strength change. RESULTS From the presurgical nTMS study, MEPs from targeted muscles were identified in 13 cases from affected hemispheres. In one case, MEP was not evoked due to a huge tumor. Among 9 cases from which intraoperative DES mapping for hand motor area was available, hotspots for APB identified by nTMS were concordant with DES-positive sites. Compared with the adjacent group (D HS-L < 10 mm, n = 6), the nonadjacent group (D HS-L ≥ 10 mm, n = 7) showed significantly better recovery of grip strength at 3 months after surgery (p < 0.01). There were correlations between D HS-L and recovery of grip strength at 1 week, 3 weeks, and 3 months after surgery (r = 0.74, 0.68, and 0.65, respectively). Postsurgical nTMS was accomplished in 13 patients. In 9 of 13 cases, nTMS-MEP from APB muscle was positive at 1 week after surgery. Excluding the case in which nTMS-MEP was negative from the presurgical nTMS study, recoveries in grip strength were compared between 2 groups, in which nTMS-MEP at 1 week after surgery was positive (n = 9) or negative (n = 3). Significant differences were observed between the 2 groups at 1 week, 3 weeks, and 3 months after surgery (p < 0.01). Positive nTMS-MEP at 1 week after surgery correlated well with the motor recovery at 1 week, 3 weeks, and 3 months after surgery (r = 0.87, 0.88, and 0.77, respectively). CONCLUSIONS Navigated TMS is a useful tool for identifying motor eloquent areas. The results of the present study have demonstrated the predictive value of nTMS in upper-extremity motor function recovery from postsurgical neurological deficits. The longer D HS-L and positive nTMS-MEP at 1 week after surgery have prognostic values of better recovery from postsurgical neurological deficits.

Repetitive Transcranial Magnetic Stimulator with Controllable Pulse Parameters

PubMed Central

Peterchev, Angel V; Murphy, David L; Lisanby, Sarah H

2013-01-01

The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10–310 μs and positive/negative phase amplitude ratio of 1–56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation by up to 82% and 57%, and decreases coil heating by up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3,000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications, and could lead to clinical applications with potentially enhanced potency. PMID:21540487

Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: a comparison with standard treatment.

PubMed

Girardi, Paolo; Rapinesi, Chiara; Chiarotti, Flavia; Kotzalidis, Georgios D; Piacentino, Daria; Serata, Daniele; Del Casale, Antonio; Scatena, Paola; Mascioli, Flavia; Raccah, Ruggero N; Brugnoli, Roberto; Digiacomantonio, Vittorio; Ferri, Vittoria Rachele; Ferracuti, Stefano; Zangen, Abraham; Angeletti, Gloria

2015-01-01

Dorsolateral prefrontal cortex (DLPFC) is dysfunctional in mood and substance use disorders. We predicted higher efficacy for add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS), compared with standard drug treatment (SDT) in patients with dysthymic disorder (DD)/alcohol use disorder (AUD) comorbidity. We carried-out a 6-month open-label study involving 20 abstinent patients with DSM-IV-TR AUD comorbid with previously developed DD. Ten patients received SDT for AUD with add-on bilateral dTMS (dTMS-AO) over the DLPFC, while another 10 received SDT alone. We rated alcohol craving with the Obsessive Compulsive Drinking Scale (OCDS), depression with the Hamilton Depression Rating Scale (HDRS), clinical status with the Clinical Global Impressions scale (CGI), and global functioning with the Global Assessment of Functioning (GAF). At the end of the 20-session dTMS period (or an equivalent period in the SDT group), craving scores and depressive symptoms in the dTMS-AO group dropped significantly more than in the SDT group (P < 0.001 and P < 0.02, respectively). High frequency bilateral DLPFC dTMS with left preference was well tolerated and found to be effective as add-on in AUD. The potential of dTMS for reducing craving in substance use disorder patients deserves to be further investigated.

How to include the variability of TMS responses in simulations: a speech mapping case study

NASA Astrophysics Data System (ADS)

De Geeter, N.; Lioumis, P.; Laakso, A.; Crevecoeur, G.; Dupré, L.

2016-11-01

When delivered over a specific cortical site, TMS can temporarily disrupt the ongoing process in that area. This allows mapping of speech-related areas for preoperative evaluation purposes. We numerically explore the observed variability of TMS responses during a speech mapping experiment performed with a neuronavigation system. We selected four cases with very small perturbations in coil position and orientation. In one case (E) a naming error occurred, while in the other cases (NEA, B, C) the subject appointed the images as smoothly as without TMS. A realistic anisotropic head model was constructed of the subject from T1-weighted and diffusion-weighted MRI. The induced electric field distributions were computed, associated to the coil parameters retrieved from the neuronavigation system. Finally, the membrane potentials along relevant white matter fibre tracts, extracted from DTI-based tractography, were computed using a compartmental cable equation. While only minor differences could be noticed between the induced electric field distributions of the four cases, computing the corresponding membrane potentials revealed different subsets of tracts were activated. A single tract was activated for all coil positions. Another tract was only triggered for case E. NEA induced action potentials in 13 tracts, while NEB stimulated 11 tracts and NEC one. The calculated results are certainly sensitive to the coil specifications, demonstrating the observed variability in this study. However, even though a tract connecting Broca’s with Wernicke’s area is only triggered for the error case, further research is needed on other study cases and on refining the neural model with synapses and network connections. Case- and subject-specific modelling that includes both electromagnetic fields and neuronal activity enables demonstration of the variability in TMS experiments and can capture the interaction with complex neural networks.

Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

PubMed Central

Chervyakov, Alexander V.; Chernyavsky, Andrey Yu.; Sinitsyn, Dmitry O.; Piradov, Michael A.

2015-01-01

Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols. PMID:26136672

Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation.

PubMed

Chervyakov, Alexander V; Chernyavsky, Andrey Yu; Sinitsyn, Dmitry O; Piradov, Michael A

2015-01-01

Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

Transcranial magnetic stimulation (TMS) responses elicited in hindlimb muscles as an assessment of synaptic plasticity in spino-muscular circuitry after chronic spinal cord injury.

PubMed

Petrosyan, Hayk A; Alessi, Valentina; Sisto, Sue A; Kaufman, Mark; Arvanian, Victor L

2017-03-06

Electromagnetic stimulation applied at the cranial level, i.e. transcranial magnetic stimulation (TMS), is a technique for stimulation and neuromodulation used for diagnostic and therapeutic applications in clinical and research settings. Although recordings of TMS elicited motor-evoked potentials (MEP) are an essential diagnostic tool for spinal cord injured (SCI) patients, they are reliably recorded from arm, and not leg muscles. Mid-thoracic contusion is a common SCI that results in locomotor impairments predominantly in legs. In this study, we used a chronic T10 contusion SCI rat model and examined whether (i) TMS-responses in hindlimb muscles can be used for evaluation of conduction deficits in cortico-spinal circuitry and (ii) if plastic changes at spinal levels will affect these responses. In this study, plastic changes of transmission in damaged spinal cord were achieved by repetitive electro-magnetic stimulation applied over the spinal level (rSEMS). Spinal electro-magnetic stimulation was previously shown to activate spinal nerves and is gaining large acceptance as a non-invasive alternative to direct current and/or epidural electric stimulation. Results demonstrate that TMS fails to induce measurable MEPs in hindlimbs of chronically SCI animals. After facilitation of synaptic transmission in damaged spinal cord was achieved with rSEMS, however, MEPs were recorded from hindlimb muscles in response to single pulse TMS stimulation. These results provide additional evidence demonstrating beneficial effects of TMS as a diagnostic technique for descending motor pathways in uninjured CNS and after SCI. This study confirms the ability of TMS to assess plastic changes of transmission occurring at the spinal level. Published by Elsevier B.V.

Thermal management system options for high power space platforms

NASA Technical Reports Server (NTRS)

Sadunas, J. A.; Lehtinen, A.; Parish, R.

1985-01-01

Thermal Management System (TMS) design options for a high power (75kWe), low earth orbit, multimodule space platform were investigated. The approach taken was to establish a baseline TMS representative of current technology, and to make incremental improvements through successive subsystem trades that lead to a candidate TMS. The TMS trades included centralized and decentralized transport, single-phase and two-phase transport, alternate working fluids, liquid loop and heat pipe radiators, deployed fixed, body mounted and steerable radiators, and thermal storage. The subsystem options were evaluated against criteria such as weight, TMS power requirement, reliability, system isothermality penalty, and growth potential.

Modulation of the cortical silent period elicited by single- and paired-pulse transcranial magnetic stimulation

PubMed Central

2013-01-01

Background The cortical silent period (CSP) elicited by transcranial magnetic stimulation (TMS) is affected by changes in TMS intensity. Some studies have shown that CSP is shortened or prolonged by short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), Those studies, however, used different TMS intensities to adjust the amplitude of the motor evoked potential (MEP). Therefore, it is unclear whether changes in CSP duration are induced by changes in TMS intensities or by SICI and ICF. The purpose of this study was to confirm the effects of muscle contractions and stimulus intensities on MEP amplitude and the duration of CSP induced by single-pulse TMS and to clarify the effects of SICI and ICF on CSP duration. MEP evoked by TMS was detected from the right first dorsal interosseous muscle in 15 healthy subjects. First, MEP and CSP were induced by single-pulse TMS with an intensity of 100% active motor threshold (AMT) at four muscle contraction levels [10%, 30%, 50%, and 70% electromyogram (EMG)]. Next, MEP and CSP were induced by seven TMS intensities (100%, 110%, 120%, 130%, 140%, 150%, and 160% AMT) during muscle contraction of 10% EMG. Finally, SICI and ICF were recorded at the four muscle contraction levels (0%, 10%, 30%, and 50% EMG). Results MEP amplitudes increased with increases in muscle contraction and stimulus intensity. However, CSP duration did not differ at different muscle contraction levels and was prolonged with increases in stimulus intensity. CSP was shortened with SICI compared with CSP induced by single-pulse TMS and with ICF at all muscle contraction levels, whereas CSP duration was not significantly changed with ICF. Conclusions We confirmed that CSP duration is affected by TMS intensity but not by the muscle contraction level. This study demonstrated that CSP is shortened with SICI, but it is not altered with ICF. These results indicate that after SICI, CSP duration is affected by the activity of inhibitory intermediate neurons that are activated by the conditioning SICI stimulus. PMID:23547559

Transcranial Magnetic Stimulation in Child Neurology: Current and Future Directions

PubMed Central

Frye, Richard E.; Rotenberg, Alexander; Ousley, Molliann; Pascual-Leone, Alvaro

2008-01-01

Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation based on the principle of electromagnetic induction, where small intracranial electric currents are generated by a powerful, rapidly changing extracranial magnetic field. Over the past 2 decades TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disease in adults, but has been used on a more limited basis in children. We reviewed the literature to identify potential diagnostic and therapeutic applications of TMS in child neurology and also its safety in pediatrics. Although TMS has not been associated with any serious side effects in children and appears to be well tolerated, general safety guidelines should be established. The potential for applications of TMS in child neurology and psychiatry is significant. Given its excellent safety profile and possible therapeutic effect, this technique should develop as an important tool in pediatric neurology over the next decade. PMID:18056688

Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks.

PubMed

Hallett, Mark; Di Iorio, Riccardo; Rossini, Paolo Maria; Park, Jung E; Chen, Robert; Celnik, Pablo; Strafella, Antonio P; Matsumoto, Hideyuki; Ugawa, Yoshikazu

2017-11-01

The goal of this review is to show how transcranial magnetic stimulation (TMS) techniques can make a contribution to the study of brain networks. Brain networks are fundamental in understanding how the brain operates. Effects on remote areas can be directly observed or identified after a period of stimulation, and each section of this review will discuss one method. EEG analyzed following TMS is called TMS-evoked potentials (TEPs). A conditioning TMS can influence the effect of a test TMS given over the motor cortex. A disynaptic connection can be tested also by assessing the effect of a pre-conditioning stimulus on the conditioning-test pair. Basal ganglia-cortical relationships can be assessed using electrodes placed in the process of deep brain stimulation therapy. Cerebellar-cortical relationships can be determined using TMS over the cerebellum. Remote effects of TMS on the brain can be found as well using neuroimaging, including both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The methods complement each other since they give different views of brain networks, and it is often valuable to use more than one technique to achieve converging evidence. The final product of this type of work is to show how information is processed and transmitted in the brain. Published by Elsevier B.V.

Scanning mutagenesis studies reveal a potential intramolecular interaction within the C-terminal half of dengue virus NS2A involved in viral RNA replication and virus assembly and secretion.

PubMed

Wu, Ren-Huang; Tsai, Ming-Han; Chao, Day-Yu; Yueh, Andrew

2015-04-01

The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMSs; pTMS1 to pTMS8). NS2A has been shown to participate in RNA replication, virion assembly, and the host antiviral response. However, the role of the amino acid residues within the pTMS regions of NS2A during the virus life cycle is poorly understood. In the study described here, we explored the function of DENV NS2A by introducing a series of double or triple alanine substitutions into the C-terminal half (pTMS4 to pTMS8) of NS2A in the context of a DENV infectious clone or subgenomic replicon. Fourteen (8 within pTMS8) of 35 NS2A mutants displayed a lethal phenotype due to impairment of RNA replication by a replicon assay. Three NS2A mutants with mutations within pTMS7, the CM20, CM25, and CM27 mutants, displayed similar phenotypes, low virus yields (>100-fold reduction), wild-type-like replicon activity, and low infectious virus-like particle yields by transient trans-packaging experiments, suggesting a defect in virus assembly and secretion. The sequencing of revertant viruses derived from CM20, CM25, and CM27 mutant viruses revealed a consensus reversion mutation, leucine (L) to phenylalanine (F), at codon 181 within pTMS7. The introduction of an L181F mutation into a full-length NS2A mutant, i.e., the CM20, CM25, and CM27 constructs, completely restored wild-type infectivity. Notably, L181F also substantially rescued the other severely RNA replication-defective mutants with mutations within pTMS4, pTMS6, and pTMS8, i.e., the CM2, CM3, CM13, CM31, and CM32 mutants. In conclusion, the results revealed the essential roles of pTMS4 to pTMS8 of NS2A in RNA replication and/or virus assembly and secretion. The intramolecular interaction between pTMS7 and pTMS4, pTMS6, or pTMS8 of the NS2A protein was also implicated. The reported characterization of the C-terminal half of dengue virus NS2A is the first comprehensive mutagenesis study to investigate the function of flavivirus NS2A involved in the steps of the virus life cycle. In particular, detailed mapping of the amino acid residues within the predicted transmembrane segments (pTMSs) of NS2A involved in RNA replication and/or virus assembly and secretion was performed. A revertant genetics study also revealed that L181F within pTMS7 is a consensus reversion mutation that rescues both RNA replication-defective and virus assembly- and secretion-defective mutants with mutations within the other three pTMSs of NS2A. Collectively, these findings elucidate the role played by NS2A during the virus life cycle, possibly through the intricate intramolecular interaction between pTMS7 and other pTMSs within the NS2A protein. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy.

PubMed

Dubin, Marc J; Mao, Xiangling; Banerjee, Samprit; Goodman, Zachary; Lapidus, Kyle A B; Kang, Guoxin; Liston, Conor; Shungu, Dikoma C

2016-04-01

GABAergic and glutamatergic neurotransmitter systems are central to the pathophysiology of depression and are potential targets of repetitive transcranial magnetic stimulation (rTMS). We assessed the effect of 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) of patients with major depressive disorder on the levels of medial prefrontal cortex (MPFC) γ-aminobutyric acid (GABA) and the combined resonance of glutamate and glutamine (Glx) as assessed in vivo with proton magnetic resonance spectroscopy ((1)H MRS). Currently depressed individuals between the ages of 23 and 68 years participated in a 5-week naturalistic, open-label treatment study of rTMS, with (1)H MRS measurements of MPFC GABA and Glx levels at baseline and following 5 weeks of the rTMS intervention. We applied rTMS pulses over the left DLPFC at 10 Hz and 80%-120% of motor threshold for 25 daily sessions, with each session consisting of 3000 pulses. We assessed therapeutic response using the 24-item Hamilton Rating Scale for Depression (HAMD24). The GABA and Glx levels are expressed as ratios of peak areas relative to the area of the synchronously acquired and similarly fitted unsuppressed voxel water signal (W). Twenty-three currently depressed individuals (7 men) participated in the study. GABA/W in the MPFC increased 13.8% (p = 0.013) in all depressed individuals. There were no significant effects of rTMS on Glx/W. GABA/W and Glx/W were highly correlated in severely depressed patients at baseline but not after TMS. The primary study limitations are the open-label design and the inclusion of participants currently taking stable regimens of antidepressant medications. These results implicate GABAergic and glutamatergic systems in the mechanism of action of rTMS for major depression, warranting further investigation in larger samples.

Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy

PubMed Central

Dubin, Marc J.; Mao, Xiangling; Banerjee, Samprit; Goodman, Zachary; Lapidus, Kyle A.B.; Kang, Guoxin; Liston, Conor; Shungu, Dikoma C.

2016-01-01

Background GABAergic and glutamatergic neurotransmitter systems are central to the pathophysiology of depression and are potential targets of repetitive transcranial magnetic stimulation (rTMS). We assessed the effect of 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) of patients with major depressive disorder on the levels of medial prefrontal cortex (MPFC) γ-aminobutyric acid (GABA) and the combined resonance of glutamate and glutamine (Glx) as assessed in vivo with proton magnetic resonance spectroscopy (1H MRS). Methods Currently depressed individuals between the ages of 23 and 68 years participated in a 5-week naturalistic, open-label treatment study of rTMS, with 1H MRS measurements of MPFC GABA and Glx levels at baseline and following 5 weeks of the rTMS intervention. We applied rTMS pulses over the left DLPFC at 10 Hz and 80%–120% of motor threshold for 25 daily sessions, with each session consisting of 3000 pulses. We assessed therapeutic response using the 24-item Hamilton Rating Scale for Depression (HAMD24). The GABA and Glx levels are expressed as ratios of peak areas relative to the area of the synchronously acquired and similarly fitted unsuppressed voxel water signal (W). Results Twenty-three currently depressed individuals (7 men) participated in the study. GABA/W in the MPFC increased 13.8% (p = 0.013) in all depressed individuals. There were no significant effects of rTMS on Glx/W. GABA/W and Glx/W were highly correlated in severely depressed patients at baseline but not after TMS. Limitations The primary study limitations are the open-label design and the inclusion of participants currently taking stable regimens of antidepressant medications. Conclusion These results implicate GABAergic and glutamatergic systems in the mechanism of action of rTMS for major depression, warranting further investigation in larger samples. PMID:26900793

Modeling transcranial magnetic stimulation from the induced electric fields to the membrane potentials along tractography-based white matter fiber tracts

NASA Astrophysics Data System (ADS)

De Geeter, Nele; Dupré, Luc; Crevecoeur, Guillaume

2016-04-01

Objective. Transcranial magnetic stimulation (TMS) is a promising non-invasive tool for modulating the brain activity. Despite the widespread therapeutic and diagnostic use of TMS in neurology and psychiatry, its observed response remains hard to predict, limiting its further development and applications. Although the stimulation intensity is always maximum at the cortical surface near the coil, experiments reveal that TMS can affect deeper brain regions as well. Approach. The explanation of this spread might be found in the white matter fiber tracts, connecting cortical and subcortical structures. When applying an electric field on neurons, their membrane potential is altered. If this change is significant, more likely near the TMS coil, action potentials might be initiated and propagated along the fiber tracts towards deeper regions. In order to understand and apply TMS more effectively, it is important to capture and account for this interaction as accurately as possible. Therefore, we compute, next to the induced electric fields in the brain, the spatial distribution of the membrane potentials along the fiber tracts and its temporal dynamics. Main results. This paper introduces a computational TMS model in which electromagnetism and neurophysiology are combined. Realistic geometry and tissue anisotropy are included using magnetic resonance imaging and targeted white matter fiber tracts are traced using tractography based on diffusion tensor imaging. The position and orientation of the coil can directly be retrieved from the neuronavigation system. Incorporating these features warrants both patient- and case-specific results. Significance. The presented model gives insight in the activity propagation through the brain and can therefore explain the observed clinical responses to TMS and their inter- and/or intra-subject variability. We aspire to advance towards an accurate, flexible and personalized TMS model that helps to understand stimulation in the connected brain and to target more focused and deeper brain regions.

Repetitive transcranial magnetic stimulation for clinical applications in neurological and psychiatric disorders: an overview.

PubMed

Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Vieira, Renata Teles; Caixeta, Leonardo; Novaes, Felipe; Marinho, Tamires; Almada, Leonardo Ferreira; Silva, Adriana Cardoso; Nardi, Antonio Egidio

2013-10-01

Neurological and psychiatric disorders are characterized by several disabling symptoms for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A method that may modulate brain activity and be viable for use in clinical practice is repetitive transcranial magnetic stimulation (rTMS). It is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Here, we focus on the basic foundation of rTMS, the main stimulation parametters, the factors that influence individual responses to rTMS and the experimental advances of rTMS that may become a viable clinical application to treat neurological and psychiatric disorders. The findings showed that rTMS can improve some symptoms associated with these conditions and might be useful for promoting cortical plasticity in patients with neurological and psychiatric disorders. However, these changes are transient and it is premature to propose these applications as realistic therapeutic options, even though the rTMS technique has been evidenced as a potential modulator of sensorimotor integration and neuroplasticity. Functional imaging of the region of interest could highlight the capacity of rTMS to bring about plastic changes of the cortical circuitry and hint at future novel clinical interventions. Thus, we recommend that further studies clearly determine the role of rTMS in the treatment of these conditions. Finally, we must remember that however exciting the neurobiological mechanisms might be, the clinical usefulness of rTMS will be determined by its ability to provide patients with neurological and psychiatric disorders with safe, long-lasting and substantial improvements in quality of life.

Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat Social Anxiety Disorder: Case Reports and a Review of the Literature

PubMed Central

Paes, Flávia; Baczynski, Tathiana; Novaes, Felipe; Marinho, Tamires; Arias-Carrión, Oscar; Budde, Henning; Sack, Alexander T.; Huston, Joseph P.; Almada, Leonardo Ferreira; Carta, Mauro; Silva, Adriana Cardoso; Nardi, Antonio E.; Machado, Sergio

2013-01-01

Objectives: Social anxiety disorder (SAD) is a common and debilitating anxiety disorders. However, few studies had been dedicated to the neurobiology underlying SAD until the last decade. Rates of non-responders to standard methods of treatment remain unsatisfactorily high of approximately 25%, including SAD. Advances in our understanding of SAD could lead to new treatment strategies. A potential non invasive therapeutic option is repetitive transcranial magnetic stimulation (rTMS). Thus, we reported two cases of SAD treated with rTMS Methods: The bibliographical search used Pubmed/Medline, ISI Web of Knowledge and Scielo databases. The terms chosen for the search were: anxiety disorders, neuroimaging, repetitive transcranial magnetic stimulation. Results: In most of the studies conducted on anxiety disorders, except SAD, the right prefrontal cortex (PFC), more specifically dorsolateral PFC was stimulated, with marked results when applying high-rTMS compared with studies stimulating the opposite side. However, according to the “valence hypothesis”, anxiety disorders might be characterized by an interhemispheric imbalance associated with increased right-hemispheric activity. With regard to the two cases treated with rTMS, we found a decrease in BDI, BAI and LSAS scores from baseline to follow-up. Conclusion: We hypothesize that the application of low-rTMS over the right medial PFC (mPFC; the main structure involved in SAD circuitry) combined with high-rTMS over the left mPFC, for at least 4 weeks on consecutive weekdays, may induce a balance in brain activity, opening an attractive therapeutic option for the treatment of SAD. PMID:24278088

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

Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra

(Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubulemore » polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like PDEs, SIRT1, or AMPK. • Resveratrol, but not Z-TMS, potently induces SHP mRNA dependent on AMPK and SIRT1.« less

Current evidence on the potential therapeutic applications of transcranial magnetic stimulation in multiple sclerosis: A systematic review of the literature.

PubMed

León Ruiz, M; Sospedra, M; Arce Arce, S; Tejeiro-Martínez, J; Benito-León, J

2018-06-10

A growing number of studies have evaluated the effects of transcranial magnetic stimulation (TMS) for the symptomatic treatment of multiple sclerosis (MS). We performed a PubMed search for articles, recent books, and recommendations from the most relevant clinical practice guidelines and scientific societies regarding the use of TMS as symptomatic treatment in MS. Excitatory electromagnetic pulses applied to the affected cerebral hemisphere allow us to optimise functional brain activity, including the transmission of nerve impulses through the demyelinated corticospinal pathway. Various studies into TMS have shown statistically significant improvements in spasticity, fatigue, lower urinary tract dysfunction, manual dexterity, gait, and cognitive deficits related to working memory in patients with MS; however, the exact level of evidence has not been defined as the results have not been replicated in a sufficient number of controlled studies. Further well-designed, randomised, controlled clinical trials involving a greater number of patients are warranted to attain a higher level of evidence in order to recommend the appropriate use of TMS in MS patients across the board. TMS acts as an adjuvant with other symptomatic and immunomodulatory treatments. Additional studies should specifically investigate the effect of conventional repetitive TMS on fatigue in these patients, something that has yet to see the light of day. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

TMS combined with EEG in genetic generalized epilepsy: A phase II diagnostic accuracy study.

PubMed

Kimiskidis, Vasilios K; Tsimpiris, Alkiviadis; Ryvlin, Philippe; Kalviainen, Reetta; Koutroumanidis, Michalis; Valentin, Antonio; Laskaris, Nikolaos; Kugiumtzis, Dimitris

2017-02-01

(A) To develop a TMS-EEG stimulation and data analysis protocol in genetic generalized epilepsy (GGE). (B) To investigate the diagnostic accuracy of TMS-EEG in GGE. Pilot experiments resulted in the development and optimization of a paired-pulse TMS-EEG protocol at rest, during hyperventilation (HV), and post-HV combined with multi-level data analysis. This protocol was applied in 11 controls (C) and 25 GGE patients (P), further dichotomized into responders to antiepileptic drugs (R, n=13) and non-responders (n-R, n=12).Features (n=57) extracted from TMS-EEG responses after multi-level analysis were given to a feature selection scheme and a Bayesian classifier, and the accuracy of assigning participants into the classes P-C and R-nR was computed. On the basis of the optimal feature subset, the cross-validated accuracy of TMS-EEG for the classification P-C was 0.86 at rest, 0.81 during HV and 0.92 at post-HV, whereas for R-nR the corresponding figures are 0.80, 0.78 and 0.65, respectively. Applying a fusion approach on all conditions resulted in an accuracy of 0.84 for the classification P-C and 0.76 for the classification R-nR. TMS-EEG can be used for diagnostic purposes and for assessing the response to antiepileptic drugs. TMS-EEG holds significant diagnostic potential in GGE. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Repeatability and reliability of muscle relaxation properties induced by motor cortical stimulation.

PubMed

Molenaar, Joery P; Voermans, Nicol C; de Jong, Lysanne A; Stegeman, Dick F; Doorduin, Jonne; van Engelen, Baziel G

2018-03-15

Impaired muscle relaxation is a feature of many neuromuscular disorders. However, there are few tests available to quantify muscle relaxation. Transcranial magnetic stimulation (TMS) of the motor cortex can induce muscle relaxation by abruptly inhibiting corticospinal drive. The aim of our study is to investigate if repeatability and reliability of TMS-induced relaxation is greater than voluntary relaxation. Furthermore, effects of sex, cooling and fatigue on muscle relaxation properties were studied. Muscle relaxation of deep finger flexors was assessed in twenty-five healthy subjects (14 M and 11 F, aged 39.1{plus minus}12.7 and 45.3{plus minus}8.7 years old, respectively) using handgrip dynamometry. All outcome measures showed greater repeatability and reliability in TMS-induced relaxation compared to voluntary relaxation. The within-subject coefficient of variability of normalized peak relaxation rate was lower in TMS-induced relaxation than in voluntary relaxation (3.0 vs 19.7% in men, and 6.1 vs 14.3% in women). The repeatability coefficient was lower (1.3 vs 6.1 s -1 in men and 2.3 vs 3.1 s -1 in women), and the intraclass correlation coefficient was higher (0.95 vs 0.53 in men and 0.78 vs 0.69 in women), for TMS-induced relaxation compared to voluntary relaxation. TMS enabled to demonstrate slowing effects of sex, muscle cooling, and muscle fatigue on relaxation properties that voluntary relaxation could not. In conclusion, repeatability and reliability of TMS-induced muscle relaxation was greater compared to voluntary muscle relaxation. TMS-induced muscle relaxation has the potential to be used in clinical practice for diagnostic purposes and therapy effect monitoring in patients with impaired muscle relaxation.

Safety and tolerability of repetitive transcranial magnetic stimulation in patients with pathologic positive sensory phenomena: a review of literature

PubMed Central

Muller, Paul A; Pascual-Leone, Alvaro; Rotenberg, Alexander

2013-01-01

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable therapeutic and diagnostic tool. rTMS appears particularly promising for disorders characterized by positive sensory phenomena attributable to alterations in sensory cortex excitability. Among these are tinnitus, auditory and visual hallucinations, and pain syndromes. OBJECTIVE Despite studies addressing rTMS efficacy in suppression of positive sensory symptoms, the safety of stimulation of potentially hyperexcitable cortex has not been fully addressed. We performed a systematic literature review and metanalysis to describe the rTMS safety profile in these disorders. METHODS Using the PubMed database, we performed an English-language literature search from January 1985 to April 2011 to review all pertinent publications. Per study, we noted and listed pertinent details. From these data we also calculated a crude per-subject risk for each adverse event. RESULTS 106 publications (n = 1815 subjects) were identified with patients undergoing rTMS for pathologic positive sensory phenomena. Adverse events associated with rTMS were generally mild and occurred in 16.7% of subjects. Seizure was the most serious adverse event, and occurred in three patients with a 0.16% crude per-subject risk. The second most severe adverse event involved aggravation of sensory phenomena, occurring in 1.54%. CONCLUSIONS The published data suggest rTMS for the treatment or diagnosis of pathologic positive sensory phenomena appears to be a relatively safe and well-tolerated procedure. However, published data are lacking in systematic reporting of adverse events, and safety risks of rTMS in these patient populations will have to be addressed in future prospective trials. PMID:22322098

Chronic Pain and PTSD: A Guide for Patients

MedlinePlus

... VA for Vets Performance Based Interviewing Clinical Trainees (Academic Affiliations) Employees & Contractors Talent Management System (TMS) VA ... stress. Search Pilots Search PILOTS *, the largest citation database on PTSD. What is PILOTS? Subscribe Sign up ...

Single-Scale Retinex Using Digital Signal Processors

NASA Technical Reports Server (NTRS)

Hines, Glenn; Rahman, Zia-Ur; Jobson, Daniel; Woodell, Glenn

2005-01-01

The Retinex is an image enhancement algorithm that improves the brightness, contrast and sharpness of an image. It performs a non-linear spatial/spectral transform that provides simultaneous dynamic range compression and color constancy. It has been used for a wide variety of applications ranging from aviation safety to general purpose photography. Many potential applications require the use of Retinex processing at video frame rates. This is difficult to achieve with general purpose processors because the algorithm contains a large number of complex computations and data transfers. In addition, many of these applications also constrain the potential architectures to embedded processors to save power, weight and cost. Thus we have focused on digital signal processors (DSPs) and field programmable gate arrays (FPGAs) as potential solutions for real-time Retinex processing. In previous efforts we attained a 21 (full) frame per second (fps) processing rate for the single-scale monochromatic Retinex with a TMS320C6711 DSP operating at 150 MHz. This was achieved after several significant code improvements and optimizations. Since then we have migrated our design to the slightly more powerful TMS320C6713 DSP and the fixed point TMS320DM642 DSP. In this paper we briefly discuss the Retinex algorithm, the performance of the algorithm executing on the TMS320C6713 and the TMS320DM642, and compare the results with the TMS320C6711.

Construction and Evaluation of Rodent-Specific rTMS Coils.

PubMed

Tang, Alexander D; Lowe, Andrea S; Garrett, Andrew R; Woodward, Robert; Bennett, William; Canty, Alison J; Garry, Michael I; Hinder, Mark R; Summers, Jeffery J; Gersner, Roman; Rotenberg, Alexander; Thickbroom, Gary; Walton, Joseph; Rodger, Jennifer

2016-01-01

Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

Localization of cortical primary motor area of the hand using navigated transcranial magnetic stimulation, BOLD and arterial spin labeling fMRI.

PubMed

Kallioniemi, Elisa; Pitkänen, Minna; Könönen, Mervi; Vanninen, Ritva; Julkunen, Petro

2016-11-01

Although the relationship between neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) has been widely studied in motor mapping, it is unknown how the motor response type or the choice of motor task affect this relationship. Centers of gravity (CoGs) and response maxima were measured with blood-oxygen-level dependent (BOLD) and arterial spin labeling (ASL) fMRI during motor tasks against nTMS CoGs and response maxima, which were mapped with motor evoked potentials (MEPs) and silent periods (SPs). No differences in motor representations (CoGs and response maxima) were observed in lateral-medial direction (p=0.265). fMRI methods localized the motor representation more posterior than nTMS (p<0.001). This was not affected by the BOLD fMRI motor task (p>0.999) nor nTMS response type (p>0.999). ASL fMRI maxima did not differ from the nTMS nor BOLD fMRI CoGs (p≥0.070), but the ASL CoG was deeper in comparison to other methods (p≤0.042). The BOLD fMRI motor task did not influence the depth of the motor representation (p≥0.745). The median Euclidean distances between the nTMS and fMRI motor representations varied between 7.7mm and 14.5mm and did not differ between the methods (F≤1.23, p≥0.318). The relationship between fMRI and nTMS mapped excitatory (MEP) and inhibitory (SP) responses, and whether the choice of motor task affects this relationship, have not been studied before. The congruence between fMRI and nTMS is good. The choice of nTMS motor response type nor BOLD fMRI motor task had no effect on this relationship. Copyright © 2016 Elsevier B.V. All rights reserved.

Dissociation of neural mechanisms underlying orientation processing in humans

PubMed Central

Ling, Sam; Pearson, Joel; Blake, Randolph

2009-01-01

Summary Orientation selectivity is a fundamental, emergent property of neurons in early visual cortex, and discovery of that property [1, 2] dramatically shaped how we conceptualize visual processing [3–6]. However, much remains unknown about the neural substrates of these basic building blocks of perception, and what is known primarily stems from animal physiology studies. To probe the neural concomitants of orientation processing in humans, we employed repetitive transcranial magnetic stimulation (rTMS) to attenuate neural responses evoked by stimuli presented within a local region of the visual field. Previous physiological studies have shown that rTMS can significantly suppress the neuronal spiking activity, hemodynamic responses, and local field potentials within a focused cortical region [7, 8]. By suppressing neural activity with rTMS, we were able to dissociate components of the neural circuitry underlying two distinct aspects of orientation processing: selectivity and contextual effects. Orientation selectivity gauged by masking was unchanged by rTMS, whereas an otherwise robust orientation repulsion illusion was weakened following rTMS. This dissociation implies that orientation processing relies on distinct mechanisms, only one of which was impacted by rTMS. These results are consistent with models positing that orientation selectivity is largely governed by the patterns of convergence of thalamic afferents onto cortical neurons, with intracortical activity then shaping population responses contained within those orientation-selective cortical neurons. PMID:19682905

Hippocampal-targeted Theta-burst Stimulation Enhances Associative Memory Formation.

PubMed

Tambini, Arielle; Nee, Derek Evan; D'Esposito, Mark

2018-06-19

The hippocampus plays a critical role in episodic memory, among other cognitive functions. However, few tools exist to causally manipulate hippocampal function in healthy human participants. Recent work has targeted hippocampal-cortical networks by performing TMS to a region interconnected with the hippocampus, posterior inferior parietal cortex (pIPC). Such hippocampal-targeted TMS enhances associative memory and influences hippocampal functional connectivity. However, it is currently unknown which stages of mnemonic processing (encoding or retrieval) are affected by hippocampal-targeted TMS. Here, we examined whether hippocampal-targeted TMS influences the initial encoding of associations (vs. items) into memory. To selectively influence encoding and not retrieval, we performed continuous theta-burst TMS before participants encoded object-location associations and assessed memory after the direct effect of stimulation dissipated. Relative to control TMS and baseline memory, pIPC TMS enhanced associative memory success and confidence. Item memory was unaffected, demonstrating a selective influence on associative versus item memory. The strength of hippocampal-pIPC functional connectivity predicted TMS-related memory benefits, which was mediated by parahippocampal and retrosplenial cortices. Our findings indicate that hippocampal-targeted TMS can specifically modulate the encoding of new associations into memory without directly influencing retrieval processes and suggest that the ability to influence associative memory may be related to the fidelity of hippocampal TMS targeting. Our results support the notion that pIPC TMS may serve as a potential tool for manipulating hippocampal function in healthy participants. Nonetheless, future work combining hippocampal-targeted continuous theta-burst TMS with neuroimaging is needed to better understand the neural basis of TMS-induced memory changes.

Catatonia with schizophrenia: From ECT to rTMS.

PubMed

Stip, E; Blain-Juste, M-E; Farmer, O; Fournier-Gosselin, M-P; Lespérance, P

2018-04-01

Electroconvulsive therapy is indicated in cases of catatonic schizophrenia following a failure of the challenge test with lorazepam or Zolpidem ® . Some patients need maintenance treatment with ECT. Repetitive Transcranial Magnetic Stimulation (rTMS) and anodal Transcranial direct-current stimulation (tDCS) might be effective against catatonia. Consider an alternative to ECT for a refractory patient. Twenty-one articles were identified mainly based on case reports series were found using search on Medline, Google Scholar, PsychInfo, CAIRNS. Key words were:"catatonia", and "rTMS", and more generally with"ECT","tDCS","Zolpidem ® ". At the end there were only six case reports with rTMS and three with tDCS. We discussed the alternative to ECT and follow up rTMS strategies illustrated by these case reports. Patients mean age was 35; numbers of previous ECT vary from zero to 556; the most common motor threshold (MT) is 80%, with two patients with 110%, the most common treatment placement is L DLPFC. In one of them, ECT was the only acute-state or maintenance treatment effective in this patient, who underwent 556 ECT sessions over 20 years. High-frequency rTMS was considered as a possible alternative, given the potential adverse effects of chronic maintenance ECT in a patient with comorbid epilepsy. rTMS treatment was 3-4×/week and over time extended to once every two weeks. A persistent objective improvement in catatonia was observed on the Bush-Francis Catatonia Rating Scale. rTMS is helpful for acute and maintenance treatment for catatonic schizophrenia who both failed multiple pharmacologic interventions and had safety concerns with continuing maintenance ECT. Clinicians should consider rTMS as a potential treatment option for refractory catatonia. Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Repetitive Transcranial Magnetic Stimulation for Clinical Applications in Neurological and Psychiatric Disorders: An Overview

PubMed Central

Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Vieira, Renata Teles; Caixeta, Leonardo; Novaes, Felipe; Marinho, Tamires; Almada, Leonardo Ferreira; Silva, Adriana Cardoso; Nardi, Antonio Egidio

2013-01-01

Neurological and psychiatric disorders are characterized by several disabling symptoms for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A method that may modulate brain activity and be viable for use in clinical practice is repetitive transcranial magnetic stimulation (rTMS). It is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Here, we focus on the basic foundation of rTMS, the main stimulation parametters, the factors that influence individual responses to rTMS and the experimental advances of rTMS that may become a viable clinical application to treat neurological and psychiatric disorders. The findings showed that rTMS can improve some symptoms associated with these conditions and might be useful for promoting cortical plasticity in patients with neurological and psychiatric disorders. However, these changes are transient and it is premature to propose these applications as realistic therapeutic options, even though the rTMS technique has been evidenced as a potential modulator of sensorimotor integration and neuroplasticity. Functional imaging of the region of interest could highlight the capacity of rTMS to bring about plastic changes of the cortical circuitry and hint at future novel clinical interventions. Thus, we recommend that further studies clearly determine the role of rTMS in the treatment of these conditions. Finally, we must remember that however exciting the neurobiological mechanisms might be, the clinical usefulness of rTMS will be determined by its ability to provide patients with neurological and psychiatric disorders with safe, long-lasting and substantial improvements in quality of life. PMID:25610279

Use of Repetitive Transcranial Magnetic Stimulation for Treatment in Psychiatry

PubMed Central

2013-01-01

The potential of noninvasive neurostimulation by repetitive transcranial magnetic stimulation (rTMS) for improving psychiatric disorders has been studied increasingly over the past two decades. This is especially the case for major depression and for auditory-verbal hallucinations in schizophrenia. The present review briefly describes the background of this novel treatment modality and summarizes evidence from clinical trials into the efficacy of rTMS for depression and hallucinations. Evidence for efficacy in depression is stronger than for hallucinations, although a number of studies have reported clinically relevant improvements for hallucinations too. Different stimulation parameters (frequency, duration, location of stimulation) are discussed. There is a paucity of research into other psychiatric disorders, but initial evidence suggests that rTMS may also hold promise for the treatment of negative symptoms in schizophrenia, obsessive compulsive disorder and post-traumatic stress disorder. It can be concluded that rTMS induces alterations in neural networks relevant for psychiatric disorders and that more research is needed to elucidate efficacy and underlying mechanisms of action. PMID:24023548

Use of repetitive transcranial magnetic stimulation for treatment in psychiatry.

PubMed

Aleman, André

2013-08-01

The potential of noninvasive neurostimulation by repetitive transcranial magnetic stimulation (rTMS) for improving psychiatric disorders has been studied increasingly over the past two decades. This is especially the case for major depression and for auditory-verbal hallucinations in schizophrenia. The present review briefly describes the background of this novel treatment modality and summarizes evidence from clinical trials into the efficacy of rTMS for depression and hallucinations. Evidence for efficacy in depression is stronger than for hallucinations, although a number of studies have reported clinically relevant improvements for hallucinations too. Different stimulation parameters (frequency, duration, location of stimulation) are discussed. There is a paucity of research into other psychiatric disorders, but initial evidence suggests that rTMS may also hold promise for the treatment of negative symptoms in schizophrenia, obsessive compulsive disorder and post-traumatic stress disorder. It can be concluded that rTMS induces alterations in neural networks relevant for psychiatric disorders and that more research is needed to elucidate efficacy and underlying mechanisms of action.

[Transcranial magnetic stimulation (TMS), inhibition processes and attention deficit/hyperactivity disorder (ADHD) - an overview].

PubMed

Hoegl, Thomas; Bender, Stephan; Buchmann, Johannes; Kratz, Oliver; Moll, Gunther H; Heinrich, Hartmut

2014-11-01

Motor system excitability can be tested by transcranial magnetic stimulation CFMS). In this article, an overview of recent methodological developments and research findings related to attention deficit/hyperactivity disorder (ADHD) is provided. Different TMS parameters that reflect the function of interneurons in the motor cortex may represent neurophysiological markers of inhibition in ADHD, particularly the so-called intracortical inhibition. In children with a high level of hyperactivity and impulsivity, intracortical inhibition was comparably low at rest as shortly before the execution of a movement. TMS-evoked potentials can also be measured in the EEG so that investigating processes of excitability is not restricted to motor areas in future studies. The effects of methylphenidate on motor system excitability may be interpreted in the sense of a 'fine-tuning' with these mainly dopaminergic effects also depending on genetic parameters (DAT1 transporter). A differentiated view on the organization of motor control can be achieved by a combined analysis of TMS parameters and event-related potentials. Applying this bimodal approach, strong evidence for a deviant implementation of motor control in children with ADHD and probably compensatory mechanisms (with involvement of the prefrontal cortex) was obtained. These findings, which contribute to a better understanding of hyperactivity/impulsivity, inhibitory processes and motor control in ADHD as well as the mechanisms of medication, underline the relevance of TMS as a neurophysiological method in ADHD research.

Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro.

PubMed

Tang, Alexander D; Hong, Ivan; Boddington, Laura J; Garrett, Andrew R; Etherington, Sarah; Reynolds, John N J; Rodger, Jennifer

2016-10-29

Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. Copyright © 2016 IBRO. All rights reserved.

In silico database screening of potential targets and pathways of compounds contained in plants used for psoriasis vulgaris.

PubMed

May, Brian H; Deng, Shiqiang; Zhang, Anthony L; Lu, Chuanjian; Xue, Charlie C L

2015-09-01

Reviews and meta-analyses of clinical trials identified plants used as traditional medicines (TMs) that show promise for psoriasis. These include Rehmannia glutinosa, Camptotheca acuminata, Indigo naturalis and Salvia miltiorrhiza. Compounds contained in these TMs have shown activities of relevance to psoriasis in experimental models. To further investigate the likely mechanisms of action of the multiple compounds in these TMs, we undertook a computer-based in silico investigation of the proteins known to be regulated by these compounds and their associated biological pathways. The proteins reportedly regulated by compounds in these four TMs were identified using the HIT (Herbal Ingredients' Targets) database. The resultant data were entered into the PANTHER (Protein ANnotation THrough Evolutionary Relationship) database to identify the pathways in which the proteins could be involved. The study identified 237 compounds in the TMs and these retrieved 287 proteins from HIT. These proteins identified 59 pathways in PANTHER with most proteins being located in the Apoptosis, Angiogenesis, Inflammation mediated by chemokine and cytokine, Gonadotropin releasing hormone receptor, and/or Interleukin signaling pathways. All four TMs contained compounds that had regulating effects on Apoptosis regulator BAX, Apoptosis regulator Bcl-2, Caspase-3, Tumor necrosis factor (TNF) or Prostaglandin G/H synthase 2 (COX2). The main proteins and pathways are primarily related to inflammation, proliferation and angiogenesis which are all processes involved in psoriasis. Experimental studies have reported that certain compounds from these TMs can regulate the expression of proteins involved in each of these pathways.

Comparison of Transcranial Magnetic Stimulation and Electroneuronography Between Bell's Palsy and Ramsay Hunt Syndrome in Their Acute Stages

PubMed Central

Hur, Dong Min; Lee, Young Hee; Kim, Sung Hoon; Park, Jung Mi; Kim, Ji Hyun; Yong, Sang Yeol; Shinn, Jong Mock; Oh, Kyung Joon

2013-01-01

Objective To examine the neurophysiologic status in patients with idiopathic facial nerve palsy (Bell's palsy) and Ramsay Hunt syndrome (herpes zoster oticus) within 7 days from onset of symptoms, by comparing the amplitude of compound muscle action potentials (CMAP) of facial muscles in electroneuronography (ENoG) and transcranial magnetic stimulation (TMS). Methods The facial nerve conduction study using ENoG and TMS was performed in 42 patients with Bell's palsy and 14 patients with Ramsay Hunt syndrome within 7 days from onset of symptoms. Denervation ratio was calculated as CMAP amplitude evoked by ENoG or TMS on the affected side as percentage of the amplitudes on the healthy side. The severity of the facial palsy was graded according to House-Brackmann facial grading scale (H-B FGS). Results In all subjects, the denervation ratio in TMS (71.53±18.38%) was significantly greater than the denervation ratio in ENoG (41.95±21.59%). The difference of denervation ratio between ENoG and TMS was significantly smaller in patients with Ramsay Hunt syndrome than in patients with Bell's palsy. The denervation ratio of ENoG or TMS did not correlated significantly with the H-B FGS. Conclusion In the electrophysiologic study for evaluation in patients with facial palsy within 7 days from onset of symptoms, ENoG and TMS are useful in gaining additional information about the neurophysiologic status of the facial nerve and may help to evaluate prognosis and set management plan. PMID:23525840

Consensus: “Can tDCS and TMS enhance motor learning and memory formation?”

PubMed Central

Reis, Janine; Robertson, Edwin; Krakauer, John W.; Rothwell, John; Marshall, Lisa; Gerloff, Christian; Wassermann, Eric; Pascual-Leone, Alvaro; Hummel, Friedhelm; Celnik, Pablo A.; Classen, Joseph; Floel, Agnes; Ziemann, Ulf; Paulus, Walter; Siebner, Hartwig R.; Born, Jan; Cohen, Leonardo G.

2009-01-01

Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this paper is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurological and psychiatric disorders. PMID:19802336

Navigated transcranial magnetic stimulation in preoperative planning for the treatment of motor area cavernous angiomas

PubMed Central

Paiva, Wellingson Silva; Fonoff, Erich Talamoni; Marcolin, Marco Antonio; Bor-Seng-Shu, Edson; Figueiredo, Eberval Gadelha; Teixeira, Manoel Jacobsen

2013-01-01

Since the introduction of microscopic techniques, radical surgery for cavernous angiomas has become a recommended treatment option. However, the treatment of motor area cavernous angioma represents a great challenge for the surgical team. Here, we describe an approach guided by frameless neuronavigation and preoperative functional mapping with transcranial magnetic stimulation (TMS), for surgical planning. We used TMS to map the motor cortex and its relationship with the angioma. We achieved complete resection of the lesions in the surgeries, while avoiding areas of motor response identified during the preoperative mapping. We verified the complete control of seizures (Engel class 1A) in the patients with previous refractory epilepsy. Postsurgery, one patient was seizure-free without medication, and two patients required only one medication for seizure control. Thus, navigated TMS appears to be a useful tool, in preoperative planning for cavernous angiomas of the motor area. PMID:24353424

Semantic priming in the motor cortex: evidence from combined repetitive transcranial magnetic stimulation and event-related potential.

PubMed

Kuipers, Jan-Rouke; van Koningsbruggen, Martijn; Thierry, Guillaume

2013-08-21

Reading action verbs is associated with activity in the motor cortices involved in performing the corresponding actions. Here, we present new evidence that the motor cortex is involved in semantic processing of bodily action verbs. In contrast to previous studies, we used a direct, nonbehavioural index of semantic processing after repetitive transcranial magnetic stimulation (rTMS). Participants saw pairs of hand-related (e.g. to grab-to point) or mouth-related (e.g. to speak-to sing) verbs, whereas semantic priming was assessed using event-related potentials. Presentation of the first verb coincided with rTMS over the participant's cortical-left hand area and event-related brain potentials were analysed time-locked to the presentation onset of the second verb. Semantic integration - indexed by the N400 brain potential - was impaired for hand-related but not for mouth-related verb pairs after rTMS. This finding provides strong evidence that the motor cortex is involved in semantic encoding of action verbs, and supports the 'embodied semantics' hypothesis.

Corrosion resistance improvement for 316L stainless steel coronary artery stents by trimethylsilane plasma nanocoatings.

PubMed

Eric Jones, John; Chen, Meng; Yu, Qingsong

2014-10-01

To improve their corrosion resistance and thus long-term biocompatibility, 316L stainless steel coronary artery stents were coated with trimethylsilane (TMS) plasma coatings of 20-25 nm in thickness. Both direct current (DC) and radio-frequency (RF) glow discharges were utilized for TMS plasma coatings and additional NH₃/O₂ plasma treatment to tailor the surface properties. X-ray photoelectron spectroscopy (XPS) was used to characterize the coating surface chemistry. It was found that both DC and RF TMS plasma coatings had Si- and C-rich composition, and the O- and N-contents on the surfaces were substantially increased after NH₃/O₂ plasma treatment. Surface contact angle measurements showed that DC TMS plasma nanocoating with NH₃/O₂ plasma treatment generated very hydrophilic surface. The corrosion resistance of TMS plasma coated stents was evaluated through potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The potentiodynamic polarization demonstrated that the TMS plasma coated stents imparted higher corrosion potential and pitting potential, as well as lower corrosion current densities as compared with uncoated controls. The surface morphology of stents before and after potentiodynamic polarization testing was analyzed with scanning electron microscopy, which indicated less corrosion on coated stents than uncoated controls. It was also noted that, from EIS data, the hydrophobic TMS plasma nanocoatings showed stable impedance modulus at 0.1 Hz after 21 day immersion in an electrolyte solution. These results suggest improved corrosion resistance of the 316L stainless steel stents by TMS plasma nanocoatings and great promise in reducing and blocking metallic ions releasing into the bloodstream. © 2014 Wiley Periodicals, Inc.

Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

PubMed Central

Kozyrev, Vladislav; Eysel, Ulf T.; Jancke, Dirk

2014-01-01

Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. To circumvent these constraints, we performed optical imaging with voltage-sensitive dye (VSD) in an animal experimental setting using anaesthetized cats. The dye signals reflect gradual changes in the cells' membrane potential across several square millimeters of cortical tissue, thus enabling direct visualization of TMS-induced neuronal population dynamics. After application of a single TMS pulse across visual cortex, brief focal activation was immediately followed by synchronous suppression of a large pool of neurons. With consecutive magnetic pulses (10 Hz), widespread activity within this “basin of suppression” increased stepwise to suprathreshold levels and spontaneous activity was enhanced. Visual stimulation after repetitive TMS revealed long-term potentiation of evoked activity. Furthermore, loss of the “deceleration–acceleration” notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions. PMID:25187557

TMSEEG: A MATLAB-Based Graphical User Interface for Processing Electrophysiological Signals during Transcranial Magnetic Stimulation.

PubMed

Atluri, Sravya; Frehlich, Matthew; Mei, Ye; Garcia Dominguez, Luis; Rogasch, Nigel C; Wong, Willy; Daskalakis, Zafiris J; Farzan, Faranak

2016-01-01

Concurrent recording of electroencephalography (EEG) during transcranial magnetic stimulation (TMS) is an emerging and powerful tool for studying brain health and function. Despite a growing interest in adaptation of TMS-EEG across neuroscience disciplines, its widespread utility is limited by signal processing challenges. These challenges arise due to the nature of TMS and the sensitivity of EEG to artifacts that often mask TMS-evoked potentials (TEP)s. With an increase in the complexity of data processing methods and a growing interest in multi-site data integration, analysis of TMS-EEG data requires the development of a standardized method to recover TEPs from various sources of artifacts. This article introduces TMSEEG, an open-source MATLAB application comprised of multiple algorithms organized to facilitate a step-by-step procedure for TMS-EEG signal processing. Using a modular design and interactive graphical user interface (GUI), this toolbox aims to streamline TMS-EEG signal processing for both novice and experienced users. Specifically, TMSEEG provides: (i) targeted removal of TMS-induced and general EEG artifacts; (ii) a step-by-step modular workflow with flexibility to modify existing algorithms and add customized algorithms; (iii) a comprehensive display and quantification of artifacts; (iv) quality control check points with visual feedback of TEPs throughout the data processing workflow; and (v) capability to label and store a database of artifacts. In addition to these features, the software architecture of TMSEEG ensures minimal user effort in initial setup and configuration of parameters for each processing step. This is partly accomplished through a close integration with EEGLAB, a widely used open-source toolbox for EEG signal processing. In this article, we introduce TMSEEG, validate its features and demonstrate its application in extracting TEPs across several single- and multi-pulse TMS protocols. As the first open-source GUI-based pipeline for TMS-EEG signal processing, this toolbox intends to promote the widespread utility and standardization of an emerging technology in brain research.

TMSEEG: A MATLAB-Based Graphical User Interface for Processing Electrophysiological Signals during Transcranial Magnetic Stimulation

PubMed Central

Atluri, Sravya; Frehlich, Matthew; Mei, Ye; Garcia Dominguez, Luis; Rogasch, Nigel C.; Wong, Willy; Daskalakis, Zafiris J.; Farzan, Faranak

2016-01-01

Concurrent recording of electroencephalography (EEG) during transcranial magnetic stimulation (TMS) is an emerging and powerful tool for studying brain health and function. Despite a growing interest in adaptation of TMS-EEG across neuroscience disciplines, its widespread utility is limited by signal processing challenges. These challenges arise due to the nature of TMS and the sensitivity of EEG to artifacts that often mask TMS-evoked potentials (TEP)s. With an increase in the complexity of data processing methods and a growing interest in multi-site data integration, analysis of TMS-EEG data requires the development of a standardized method to recover TEPs from various sources of artifacts. This article introduces TMSEEG, an open-source MATLAB application comprised of multiple algorithms organized to facilitate a step-by-step procedure for TMS-EEG signal processing. Using a modular design and interactive graphical user interface (GUI), this toolbox aims to streamline TMS-EEG signal processing for both novice and experienced users. Specifically, TMSEEG provides: (i) targeted removal of TMS-induced and general EEG artifacts; (ii) a step-by-step modular workflow with flexibility to modify existing algorithms and add customized algorithms; (iii) a comprehensive display and quantification of artifacts; (iv) quality control check points with visual feedback of TEPs throughout the data processing workflow; and (v) capability to label and store a database of artifacts. In addition to these features, the software architecture of TMSEEG ensures minimal user effort in initial setup and configuration of parameters for each processing step. This is partly accomplished through a close integration with EEGLAB, a widely used open-source toolbox for EEG signal processing. In this article, we introduce TMSEEG, validate its features and demonstrate its application in extracting TEPs across several single- and multi-pulse TMS protocols. As the first open-source GUI-based pipeline for TMS-EEG signal processing, this toolbox intends to promote the widespread utility and standardization of an emerging technology in brain research. PMID:27774054

Lamotrigine and levetiracetam exert a similar modulation of TMS-evoked EEG potentials.

PubMed

Premoli, Isabella; Biondi, Andrea; Carlesso, Sara; Rivolta, Davide; Richardson, Mark P

2017-01-01

Antiepileptic drug (AED) treatment failures may occur because there is insufficient drug in the brain or because of a lack of relevant therapeutic response. Until now it has not been possible to measure these factors. It has been recently shown that the combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) can measure the effects of drugs in healthy volunteers. TMS-evoked EEG potentials (TEPs) comprise a series of positive and negative deflections that can be specifically modulated by drugs with a well-known mode of action targeting inhibitory neurotransmission. Therefore, we hypothesized that TMS-EEG can detect effects of two widely used AEDs, lamotrigine and levetiracetam, in healthy volunteers. Fifteen healthy subjects participated in a pseudo-randomized, placebo-controlled, double-blind, crossover design, using a single oral dose of lamotrigine (300 mg) and levetiracetam (3,000 mg). TEPs were recorded before and 120 min after drug intake, and the effects of drugs on the amplitudes of TEP components were statistically evaluated. A nonparametric cluster-based permutation analysis of TEP amplitudes showed that AEDs both increased the amplitude of the negative potential at 45 msec after stimulation (N45) and suppressed the positive peak at 180 msec (P180). This is the first demonstration of AED-induced modulation of TMS-EEG measures. Despite the different mechanism of action that lamotrigine and levetiracetam exert at the molecular level, both AEDs impact the TMS-EEG response in a similar way. These TMS-EEG fingerprints observed in healthy subjects are candidate predictive markers of treatment response in patients on monotherapy with lamotrigine and levetiracetam. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders.

PubMed

Slotema, Christina W; Blom, Jan Dirk; Hoek, Hans W; Sommer, Iris E C

2010-07-01

Repetitive transcranial magnetic stimulation (rTMS) is a safe treatment method with few side effects. However, efficacy for various psychiatric disorders is currently not clear. A literature search was performed from 1966 through October 2008 using PubMed, Ovid Medline, Embase Psychiatry, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and PsycINFO. The following search terms were used: transcranial magnetic stimulation, TMS, repetitive TMS, psychiatry, mental disorder, psychiatric disorder, anxiety disorder, attention-deficit hyperactivity disorder, bipolar disorder, catatonia, mania, depression, obsessive-compulsive disorder, psychosis, posttraumatic stress disorder, schizophrenia, Tourette's syndrome, bulimia nervosa, and addiction. Data were obtained from randomized, sham-controlled studies of rTMS treatment for depression (34 studies), auditory verbal hallucinations (AVH, 7 studies), negative symptoms in schizophrenia (7 studies), and obsessive-compulsive disorder (OCD, 3 studies). Studies of rTMS versus electroconvulsive treatment (ECT, 6 studies) for depression were meta-analyzed. Standardized mean effect sizes of rTMS versus sham were computed based on pretreatment-posttreatment comparisons. The mean weighted effect size of rTMS versus sham for depression was 0.55 (P < .001). Monotherapy with rTMS was more effective than rTMS as adjunctive to antidepressant medication. ECT was superior to rTMS in the treatment of depression (mean weighted effect size -0.47, P = .004). In the treatment of AVH, rTMS was superior to sham treatment, with a mean weighted effect size of 0.54 (P < .001). The mean weighted effect size for rTMS versus sham in the treatment of negative symptoms in schizophrenia was 0.39 (P = .11) and for OCD, 0.15 (P = .52). Side effects were mild, yet more prevalent with high-frequency rTMS at frontal locations. It is time to provide rTMS as a clinical treatment method for depression, for auditory verbal hallucinations, and possibly for negative symptoms. We do not recommend rTMS for the treatment of OCD. (c) Copyright 2010 Physicians Postgraduate Press, Inc.

Application of noninvasive brain stimulation for post-stroke dysphagia rehabilitation.

PubMed

Wang, Zhuo; Song, Wei-Qun; Wang, Liang

2017-02-01

Noninvasive brain stimulation (NIBS), commonly consisting of transcranial magnetic stimulation (TMS), transcranial direct-current stimulation (tDCS), as well as paired associative stimulation (PAS), has attracted increased interest and been applied experimentally in the treatment of post-stroke dysphagia (PSD). This review presented a synopsis of the current research for the application of NIBS on PSD. The intention here was to understand the current research progress and limitations in this field and to stimulate potential research questions not yet investigated for the application of NIBS on patients with PSD. Here we successively reviewed advances of repetitive TMS (rTMS), tDCS, and PAS techniques on both healthy participants and PSD patients in three aspects, including scientific researches about dysphagia mechanism, applied studies about stimulation parameters, and clinical trials about their therapeutic effects. The techniques of NIBS, especially rTMS, have been used by the researchers to explore the different mechanisms between swallowing recovery and extremity rehabilitation. The key findings included the important role of intact hemisphere reorganization for PSD recovery, and the use of NIBS on the contra-lesional side as a therapeutic potential for dysphagia rehabilitation. Though significant results were achieved in most studies by using NIBS on swallowing rehabilitation, it is still difficult to draw conclusions for the efficacy of these neurostimulation techniques, considering the great disparities between studies. Copyright © 2016. Published by Elsevier Taiwan.

Repetitive Transcranial Magnetic Stimulation (rTMS) Therapy in Parkinson Disease: A Meta-Analysis.

PubMed

Wagle Shukla, Aparna; Shuster, Jonathan J; Chung, Jae Woo; Vaillancourt, David E; Patten, Carolynn; Ostrem, Jill; Okun, Michael S

2016-04-01

Several studies have reported repetitive transcranial magnetic stimulation (rTMS) therapy as an effective treatment for the control of motor symptoms in Parkinson disease. The objective of the study is to quantify the overall efficacy of this treatment. Systematic review and meta-analysis. We reviewed the literature on clinical rTMS trials in Parkinson disease since the technique was introduced in 1980. We used the following databases: MEDLINE, Web of Science, Cochrane, and CINAHL. Patients with Parkinson disease who were participating in prospective clinical trials that included an active arm and a control arm and change in motor scores on Unified Parkinson's Disease Rating Scale as the primary outcome. We pooled data from 21 studies that met these criteria. We then analyzed separately the effects of low- and high-frequency rTMS on clinical motor improvements. The overall pooled mean difference between treatment and control groups in the Unified Parkinson's Disease Rating Scale motor score was significant (4.0 points, 95% confidence interval, 1.5, 6.7; P = .005). rTMS therapy was effective when low-frequency stimulation (≤ 1 Hz) was used with a pooled mean difference of 3.3 points (95% confidence interval 1.6, 5.0; P = .005). There was a trend for significance when high-frequency stimulation (≥ 5 Hz) studies were evaluated with a pooled mean difference of 3.9 points (95% confidence interval, -0.7, 8.5; P = .08). rTMS therapy demonstrated benefits at short-term follow-up (immediately after a treatment protocol) with a pooled mean difference of 3.4 points (95% confidence interval, 0.3, 6.6; P = .03) as well as at long-term follow-up (average follow-up 6 weeks) with mean difference of 4.1 points (95% confidence interval, -0.15, 8.4; P = .05). There were insufficient data to statistically analyze the effects of rTMS when we specifically examined bradykinesia, gait, and levodopa-induced dyskinesia using quantitative methods. rTMS therapy in patients with Parkinson disease results in mild-to-moderate motor improvements and has the potential to be used as an adjunct therapy for the treatment of Parkinson disease. Future large, sample studies should be designed to isolate the specific clinical features of Parkinson disease that respond well to rTMS therapy. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Transcranial magnetic stimulation: physics, electrophysiology, and applications.

PubMed

Fatemi-Ardekani, Ali

2008-01-01

Transcranial magnetic stimulation (TMS) is a noninvasive technique used to stimulate the brain. This review will examine the fundamental principles of physics upon which magnetic stimulation is based, the design considerations of the TMS device, and hypotheses about its electrophysiological effects resulting in neuromodulation. TMS is valuable in neurophysiology research and has significant therapeutic potential in clinical neurology and psychiatry. While TMS can modify neuronal currents in the brain, its underlying mechanism remains unknown. Salient applications are included and some suggestions are outlined for future development of magnetic stimulators that could lead to more effective neuronal stimulation and therefore better therapeutic and diagnostic applications.

Chronic treatment with rivastigmine in patients with Alzheimer's disease: a study on primary motor cortex excitability tested by 5 Hz-repetitive transcranial magnetic stimulation.

PubMed

Trebbastoni, A; Gilio, F; D'Antonio, F; Cambieri, C; Ceccanti, M; de Lena, C; Inghilleri, M

2012-05-01

To investigate changes in cortical excitability and short-term synaptic plasticity we delivered 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in 11 patients with mild-to-moderate Alzheimer's disease (AD) before and after chronic therapy with rivastigmine. Resting motor threshold (RMT), motor evoked potential (MEP), cortical silent period (CSP) after single stimulus and MEP facilitation during rTMS trains were tested three times during treatment. All patients underwent neuropsychological tests before and after receiving rivastigmine. rTMS data in patients were compared with those from age-matched healthy controls. At baseline, RMT was significantly lower in patients than in controls whereas CSP duration and single MEP amplitude were similar in both groups. In patients, rTMS failed to induce the normal MEP facilitation during the trains. Chronic rivastigmine intake significantly increased MEP amplitude after a single stimulus, whereas it left the other neurophysiological variables studied unchanged. No significant correlation was found between patients' neuropsychological test scores and TMS measures. Chronic treatment with rivastigmine has no influence on altered cortical excitability and short-term synaptic plasticity as tested by 5 Hz-rTMS. The limited clinical benefits related to cholinesterase inhibitor therapy in patients with AD depend on factors other than improved plasticity within the cortical glutamatergic circuits. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Atlas of optimal coil orientation and position for TMS: A computational study.

PubMed

Gomez-Tames, Jose; Hamasaka, Atsushi; Laakso, Ilkka; Hirata, Akimasa; Ugawa, Yoshikazu

2018-04-17

Transcranial magnetic stimulation (TMS) activates target brain structures in a non-invasive manner. The optimal orientation of the TMS coil for the motor cortex is well known and can be estimated using motor evoked potentials. However, there are no easily measurable responses for activation of other cortical areas and the optimal orientation for these areas is currently unknown. This study investigated the electric field strength, optimal coil orientation, and relative locations to optimally stimulate the target cortex based on computed electric field distributions. A total of 518,616 stimulation scenarios were studied using realistic head models (2401 coil locations × 12 coil angles × 18 head models). Inter-subject registration methods were used to generate an atlas of optimized TMS coil orientations on locations on the standard brain. We found that the maximum electric field strength is greater in primary somatosensory cortex and primary motor cortex than in other cortical areas. Additionally, a universal optimal coil orientation applicable to most subjects is more feasible at the primary somatosensory cortex and primary motor cortex. We confirmed that optimal coil angle follows the anatomical shape of the hand motor area to realize personalized optimization of TMS. Finally, on average, the optimal coil positions for TMS on the scalp deviated 5.5 mm from the scalp points with minimum cortex-scalp distance. This deviation was minimal at the premotor cortex and primary motor cortex. Personalized optimal coil orientation is preferable for obtaining the most effective stimulation. Copyright © 2018. Published by Elsevier Inc.

Acute and chronic effects of hypercalcaemia on cortical excitability as studied by 5 Hz repetitive transcranial magnetic stimulation.

PubMed

Iacovelli, Elisa; Gilio, Francesca; Mascia, Maria Lucia; Scillitani, Alfredo; Romagnoli, Elisabetta; Pichiorri, Floriana; Fucile, Sergio; Minisola, Salvatore; Inghilleri, Maurizio

2011-04-01

We designed the present study to disclose changes in cortical excitability in humans with hypercalcaemia, by delivering repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1). In 22 patients with chronic hypercalcaemia related to primary hyperparathyroidism and 22 age-matched healthy subjects 5 Hz-rTMS was delivered at rest and during a sustained voluntary contraction of the target muscle. Changes in the resting motor threshold (RMT), motor evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured and compared in patients and healthy controls. Two of the 22 patients were re-tested after parathyroidectomy when serum calcium had normalized. In a subgroup of healthy subjects, changes in the rTMS parameters were tested before and after acute hypercalcaemia. No significant difference between healthy normocalcaemic subjects and chronic hypercalcaemic patients was found in the RMT values and MEP amplitude and CSP duration evoked by the first stimulus of the trains. During the course of 5 Hz-rTMS trains, MEP size increased significantly less in patients with chronic hypercalcaemia than in healthy subjects, whereas the CSP duration lengthened to a similar extent in both groups. In the two patients studied after parathyroidectomy, rTMS elicited a normal MEP amplitude facilitation. Our findings indicate that acute hypercalcaemia significantly decreased the MEP amplitude facilitation. Given that 5 Hz-rTMS modulates cortical excitability through mechanisms resembling short-term synaptic enhancement, the reduction of MEP amplitude facilitation by hypercalcaemia may be related to Ca2+-dependent changes in synaptic plasticity.

Acute and chronic effects of hypercalcaemia on cortical excitability as studied by 5 Hz repetitive transcranial magnetic stimulation

PubMed Central

Iacovelli, Elisa; Gilio, Francesca; Mascia, Maria Lucia; Scillitani, Alfredo; Romagnoli, Elisabetta; Pichiorri, Floriana; Fucile, Sergio; Minisola, Salvatore; Inghilleri, Maurizio

2011-01-01

Abstract We designed the present study to disclose changes in cortical excitability in humans with hypercalcaemia, by delivering repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1). In 22 patients with chronic hypercalcaemia related to primary hyperparathyroidism and 22 age-matched healthy subjects 5 Hz-rTMS was delivered at rest and during a sustained voluntary contraction of the target muscle. Changes in the resting motor threshold (RMT), motor evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured and compared in patients and healthy controls. Two of the 22 patients were re-tested after parathyroidectomy when serum calcium had normalized. In a subgroup of healthy subjects, changes in the rTMS parameters were tested before and after acute hypercalcaemia. No significant difference between healthy normocalcaemic subjects and chronic hypercalcaemic patients was found in the RMT values and MEP amplitude and CSP duration evoked by the first stimulus of the trains. During the course of 5 Hz-rTMS trains, MEP size increased significantly less in patients with chronic hypercalcaemia than in healthy subjects, whereas the CSP duration lengthened to a similar extent in both groups. In the two patients studied after parathyroidectomy, rTMS elicited a normal MEP amplitude facilitation. Our findings indicate that acute hypercalcaemia significantly decreased the MEP amplitude facilitation. Given that 5 Hz-rTMS modulates cortical excitability through mechanisms resembling short-term synaptic enhancement, the reduction of MEP amplitude facilitation by hypercalcaemia may be related to Ca2+-dependent changes in synaptic plasticity. PMID:21300754

Transcranial magnetic stimulation of the left dorsolateral prefrontal cortex decreases cue-induced nicotine craving and EEG delta power.

PubMed

Pripfl, Jürgen; Tomova, Livia; Riecansky, Igor; Lamm, Claus

2014-01-01

TMS has high potential as smoking cessation treatment. However, the neural mechanisms underlying TMS induced reduction of tobacco craving remain unclear. Electroencephalographic (EEG) delta frequency has been associated with the activity of the dopaminergic brain reward system, which is crucial for nicotine induced effects, and decreases after nicotine admission in smokers. The aim of this study was to investigate EEG delta power changes induced by hf rTMS of the left dorsolateral prefrontal cortex (DLPFC) in nicotine deprived smokers and it's relation to cue-induced nicotine craving. Fourteen healthy smokers meeting ICD-10 criteria for tobacco addiction participated in this within-subject sham controlled study. Participants had to abstain from smoking 6 h before the experiment. Effects of high-frequency repetitive TMS (hf rTMS) (10 Hz) for verum (left DLPFC) and sham (vertex) stimulations on cue-induced nicotine craving and resting state EEG delta power were assessed before and three times within 40 min after rTMS. Both craving (P = 0.046) and EEG delta power (P = 0.048) were significantly lower after verum stimulation compared to sham stimulation across the whole post stimulation time period assessed. However, changes of craving ratings and delta power did not correlate. Hf rTMS applied to the left DLPFC reduces nicotine craving in short-term abstinent smokers. Changes in delta activity support the idea that stimulation induced effects are mediated by the dopaminergic brain reward system, which presumably plays a prominent, but probably not exclusive, role in this stimulation induced behavioral modulation, making this method a promising smoking cessation treatment candidate. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional representation of living and nonliving domains across the cerebral hemispheres: a combined event-related potential/transcranial magnetic stimulation study.

PubMed

Fuggetta, Giorgio; Rizzo, Silvia; Pobric, Gorana; Lavidor, Michal; Walsh, Vincent

2009-02-01

Transcranial magnetic stimulation (TMS) over the left hemisphere has been shown to disrupt semantic processing but, to date, there has been no direct demonstration of the electrophysiological correlates of this interference. To gain insight into the neural basis of semantic systems, and in particular, study the temporal and functional organization of object categorization processing, we combined repetitive TMS (rTMS) and ERPs. Healthy volunteers performed a picture-word matching task in which Snodgrass drawings of natural (e.g., animal) and artifactual (e.g., tool) categories were associated with a word. When short trains of high-frequency rTMS were applied over Wernicke's area (in the region of the CP5 electrode) immediately before the stimulus onset, we observed delayed response times to artifactual items, and thus, an increased dissociation between natural and artifactual domains. This behavioral effect had a direct ERP correlate. In the response period, the stimuli from the natural domain elicited a significant larger late positivity complex than those from the artifactual domain. These differences were significant over the centro-parietal region of the right hemisphere. These findings demonstrate that rTMS interferes with post-perceptual categorization processing of natural and artifactual stimuli that involve separate subsystems in distinct cortical areas.

Is it time to introduce repetitive transcranial magnetic stimulation into standard clinical practice for the treatment of depressive disorders?

PubMed

Fitzgerald, Paul

2003-02-01

To examine issues relating to the potential introduction of repetitive transcranial magnetic stimulation (rTMS) into clinical practice as a treatment for depression. A review of the outcomes literature accompanied by an analysis of issues relating to the potential advantages and pitfalls of the introduction of rTMS as a treatment strategy. Evidence is progressively accumulating that rTMS has antidepressant properties that are clinically relevant. These effects are biologically plausible and supported by basic research. Patients with therapy-resistant depression have few treatment alternatives and experience significant suffering, thus justifying the early introduction of a new treatment such as rTMS for this patient group. However, this must be balanced by a need to foster considerable further research and not to raise expectations unreasonably. It is timely for rTMS to be made more available to patients with treatment-resistant mood disorders. This need not be limited to clinical research trials but should only occur in medical settings where continual evaluation and research is conducted.

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain

PubMed Central

Gomes-Osman, Joyce; Indahlastari, Aprinda; Fried, Peter J.; Cabral, Danylo L. F.; Rice, Jordyn; Nissim, Nicole R.; Aksu, Serkan; McLaren, Molly E.; Woods, Adam J.

2018-01-01

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

Development of Commercial Thermo-sensitive Genic Male Sterile Rice Accelerates Hybrid Rice Breeding Using the CRISPR/Cas9-mediated TMS5 Editing System.

PubMed

Zhou, Hai; He, Ming; Li, Jing; Chen, Liang; Huang, Zhifeng; Zheng, Shaoyan; Zhu, Liya; Ni, Erdong; Jiang, Dagang; Zhao, Bingran; Zhuang, Chuxiong

2016-11-22

Hybrid rice breeding offers an important strategy to improve rice production, in which the cultivation of a male sterile line is the key to the success of cross-breeding. CRISPR/Cas9 systems have been widely used in target-site genome editing, whereas their application for crop genetic improvement has been rarely reported. Here, using the CRISPR/Cas9 system, we induced specific mutations in TMS5, which is the most widely applied thermo-sensitive genic male sterility (TGMS) gene in China, and developed new "transgene clean" TGMS lines. We designed 10 target sites in the coding region of TMS5 for targeted mutagenesis using the CRISPR/Cas9 system and assessed the potential rates of on- and off-target effects. Finally, we established the most efficient construct, the TMS5ab construct, for breeding potentially applicable "transgene clean" TGMS lines. We also discussed factors that affect the editing efficiency according to the characteristics of different target sequences. Notably, using the TMS5ab construct, we developed 11 new "transgene clean" TGMS lines with potential applications in hybrid breeding within only one year in both rice subspecies. The application of our system not only significantly accelerates the breeding of sterile lines but also facilitates the exploitation of heterosis.

Effects of low frequency rTMS treatment on brain networks for inner speech in patients with schizophrenia and auditory verbal hallucinations.

PubMed

Bais, Leonie; Liemburg, Edith; Vercammen, Ans; Bruggeman, Richard; Knegtering, Henderikus; Aleman, André

2017-08-01

Efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) targeting the temporo-parietal junction (TPJ) for the treatment of auditory verbal hallucinations (AVH) remains under debate. We assessed the influence of a 1Hz rTMS treatment on neural networks involved in a cognitive mechanism proposed to subserve AVH. Patients with schizophrenia (N=24) experiencing medication-resistant AVH completed a 10-day 1Hz rTMS treatment. Participants were randomized to active stimulation of the left or bilateral TPJ, or sham stimulation. The effects of rTMS on neural networks were investigated with an inner speech task during fMRI. Changes within and between neural networks were analyzed using Independent Component Analysis. rTMS of the left and bilateral TPJ areas resulted in a weaker network contribution of the left supramarginal gyrus to the bilateral fronto-temporal network. Left-sided rTMS resulted in stronger network contributions of the right superior temporal gyrus to the auditory-sensorimotor network, right inferior gyrus to the left fronto-parietal network, and left middle frontal gyrus to the default mode network. Bilateral rTMS was associated with a predominant inhibitory effect on network contribution. Sham stimulation showed different patterns of change compared to active rTMS. rTMS of the left temporo-parietal region decreased the contribution of the left supramarginal gyrus to the bilateral fronto-temporal network, which may reduce the likelihood of speech intrusions. On the other hand, left rTMS appeared to increase the contribution of functionally connected regions involved in perception, cognitive control and self-referential processing. These findings hint to potential neural mechanisms underlying rTMS for hallucinations but need corroboration in larger samples. Copyright © 2017 Elsevier Inc. All rights reserved.

The characteristic and changes of the event-related potentials (ERP) and brain topographic maps before and after treatment with rTMS in subjective tinnitus patients.

PubMed

Yang, Haidi; Xiong, Hao; Yu, Rongjun; Wang, Changming; Zheng, Yiqing; Zhang, Xueyuan

2013-01-01

To compare the event-related potentials (ERPs) and brain topographic maps characteristic and change in normal controls and subjective tinnitus patients before and after repetitive transcranial magnetic stimulation (rTMS) treatment. The ERPs and brain topographic maps elicited by target stimulus were compared before and after 1-week treatment with rTMS in 20 subjective tinnitus patients and 16 healthy controls. Before rTMS, target stimulus elicited a larger N1 component than the standard stimuli (repeating sounds)in control group but not in tinnitus patients. Instead, the tinnitus group pre-treatment exhibited larger amplitude of N1 in response to standard stimuli than to deviant stimuli. Furthermore tinnitus patients had smaller mismatch negativity (MMN) and late discriminative negativity (LDN)component at Fz compared with the control group. After rTMS treatment, tinnitus patients showed increased N1 response to deviant stimuli and larger MMN and LDN compared with pre-treatment. The topographic maps for the tinnitus group before rTMS -treatment demonstrated global asymmetry between the left and right cerebral hemispheres with more negative activities in left side and more positive activities in right side. In contrast, the brain topographic maps for patients after rTMS-treatment and controls seem roughly symmetrical. The ERP amplitudes and brain topographic maps in post-treatment patient group showed no significant difference with those in controls. The characterical changes in ERP and brain topographic maps in tinnitus patients maybe related with the electrophysiological mechanism of tinnitus induction and development. It can be used as an objective biomarker for the evaluation of auditory central in subjective tinnitus patients. These findings support the notion that rTMS treatment in tinnitus patients may exert a beneficial effect.

Corrosion resistance improvement for 316L stainless steel coronary artery stents by trimethylsilane plasma nanocoatings

PubMed Central

Jones, John Eric; Chen, Meng; Yu, Qingsong

2015-01-01

To improve their corrosion resistance and thus long-term biocompatibility, 316L stainless steel coronary artery stents were coated with trimethylsilane (TMS) plasma coatings of 20–25 nm in thickness. Both direct current (DC) and radio-frequency (RF) glow discharges were utilized for TMS plasma coatings and additional NH3/O2 plasma treatment to tailor the surface properties. X-ray photoelectron spectroscopy (XPS) was used to characterize the coating surface chemistry. It was found that both DC and RF TMS plasma coatings had Si- and C-rich composition, and the O-and N-contents on the surfaces were substantially increased after NH3/O2 plasma treatment. Surface contact angle measurements showed that DC TMS plasma nanocoating with NH3/O2 plasma treatment generated very hydrophilic surface. The corrosion resistance of TMS plasma coated stents was evaluated through potentiodynamic polarization and electro-chemical impedance spectroscopy (EIS) techniques. The potentiodynamic polarization demonstrated that the TMS plasma coated stents imparted higher corrosion potential and pitting potential, as well as lower corrosion current densities as compared with uncoated controls. The surface morphology of stents before and after potentiodynamic polarization testing was analyzed with scanning electron microscopy, which indicated less corrosion on coated stents than uncoated controls. It was also noted that, from EIS data, the hydrophobic TMS plasma nanocoatings showed stable impedance modulus at 0.1 Hz after 21 day immersion in an electrolyte solution. These results suggest improved corrosion resistance of the 316L stainless steel stents by TMS plasma nanocoatings and great promise in reducing and blocking metallic ions releasing into the bloodstream. PMID:24500866

Double shroud delivery of silica precursor for reducing hexavalent chromium in welding fume.

PubMed

Wang, Jun; Kalivoda, Mark; Guan, Jianying; Theodore, Alexandros; Sharby, Jessica; Wu, Chang-Yu; Paulson, Kathleen; Es-Said, Omar

2012-01-01

The welding process yields a high concentration of nanoparticles loaded with hexavalent chromium (Cr(6+)), a known human carcinogen. Previous studies have demonstrated that using tetramethylsilane (TMS) as a shielding gas additive can significantly reduce the Cr(6+) concentration in welding fume particles. In this study, a novel insulated double shroud torch (IDST) was developed to further improve the reduction of airborne Cr(6+) concentration by separating the flows of the primary shielding gas and the TMS carrier gas. Welding fumes were collected from a welding chamber in the laboratory and from a fixed location near the welding arc in a welding facility. The Cr(6+) content was analyzed with ion chromatography and X-ray photoelectron spectroscopy (XPS). Results from the chamber sampling demonstrated that the addition of 3.2 ≈ 5.1% of TMS carrier gas to the primary shielding gas resulted in more than a 90% reduction of airborne Cr(6+) under all shielding gas flow rates. The XPS result confirmed complete elimination of Cr(6+) inside the amorphous silica shell. Adding 100 ≈ 1000 ppm of nitric oxide or carbon monoxide to the shielding gas could also reduce Cr(6+) concentrations up to 57% and 35%, respectively; however, these reducing agents created potential hazards from the release of unreacted agents. Results of the field test showed that the addition of 1.6% of TMS carrier gas to the primary shielding gas reduced Cr(6+) concentration to the limitation of detection (1.1 μg/m(3)). In a worst-case scenario, if TMS vapor leaked into the environment without decomposition and ventilation, the estimated TMS concentration in the condition of field sampling would be a maximum 5.7 ppm, still well below its flammability limit (1%). Based on a previously developed cost model, the use of TMS increases the general cost by 3.8%. No visual deterioration of weld quality caused by TMS was found, although further mechanical testing is necessary.

A high-resolution computational localization method for transcranial magnetic stimulation mapping.

PubMed

Aonuma, Shinta; Gomez-Tames, Jose; Laakso, Ilkka; Hirata, Akimasa; Takakura, Tomokazu; Tamura, Manabu; Muragaki, Yoshihiro

2018-05-15

Transcranial magnetic stimulation (TMS) is used for the mapping of brain motor functions. The complexity of the brain deters determining the exact localization of the stimulation site using simplified methods (e.g., the region below the center of the TMS coil) or conventional computational approaches. This study aimed to present a high-precision localization method for a specific motor area by synthesizing computed non-uniform current distributions in the brain for multiple sessions of TMS. Peritumoral mapping by TMS was conducted on patients who had intra-axial brain neoplasms located within or close to the motor speech area. The electric field induced by TMS was computed using realistic head models constructed from magnetic resonance images of patients. A post-processing method was implemented to determine a TMS hotspot by combining the computed electric fields for the coil orientations and positions that delivered high motor-evoked potentials during peritumoral mapping. The method was compared to the stimulation site localized via intraoperative direct brain stimulation and navigated TMS. Four main results were obtained: 1) the dependence of the computed hotspot area on the number of peritumoral measurements was evaluated; 2) the estimated localization of the hand motor area in eight non-affected hemispheres was in good agreement with the position of a so-called "hand-knob"; 3) the estimated hotspot areas were not sensitive to variations in tissue conductivity; and 4) the hand motor areas estimated by this proposal and direct electric stimulation (DES) were in good agreement in the ipsilateral hemisphere of four glioma patients. The TMS localization method was validated by well-known positions of the "hand-knob" in brains for the non-affected hemisphere, and by a hotspot localized via DES during awake craniotomy for the tumor-containing hemisphere. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke.

PubMed

Niimi, Masachika; Hashimoto, Kenji; Kakuda, Wataru; Miyano, Satoshi; Momosaki, Ryo; Ishima, Tamaki; Abo, Masahiro

2016-01-01

Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism. To investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis. Poststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels. Two-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (ρ = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism. The combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery.

A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy.

PubMed

Loo, Colleen K; Mitchell, Philip B

2005-11-01

There is a growing interest in extending the use of repetitive transcranial magnetic stimulation (rTMS) beyond research centres to the widespread clinical treatment of depression. Thus it is timely to critically review the evidence for the efficacy of rTMS as an antidepressant treatment. Factors relevant to the efficacy of rTMS are discussed along with the implications of these for the further optimization of rTMS. Clinical trials of the efficacy of rTMS in depressed subjects are summarized and reviewed, focusing mainly on sham-controlled studies and meta-analyses published to date. There is a fairly consistent statistical evidence for the superiority of rTMS over a sham control, though the degree of clinical improvement is not large. However, this data is derived mainly from two-week comparisons of rTMS versus sham, and evidence suggests greater efficacy with longer treatment courses. Studies so far have also varied greatly in approaches to rTMS stimulation (with respect to stimulation site, stimulus parameters etc) with little empirical evidence to inform on the relative merits of these approaches. Only studies published in English were reviewed. Many of the studies in the literature had small sample sizes and different methodologies, making comparisons between studies difficult. Current published studies and meta-analyses have evaluated the efficacy of rTMS as given in treatment paradigms that are almost certainly suboptimal (e.g of two weeks' duration). While the data nevertheless supports positive outcomes for rTMS, there is much scope for the further refinement and development of rTMS as an antidepressant treatment. Ongoing research is critical for optimizing the efficacy of rTMS.

Noninvasive Brain Stimulation in Pediatric ADHD: A Review

PubMed Central

Rubio, Belen; Boes, Aaron D.; Laganiere, Simon; Rotenberg, Alexander; Jeurissen, Danique; Pascual-Leone, Alvaro

2015-01-01

Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in the pediatric population. The clinical management of ADHD is currently limited by a lack of reliable diagnostic biomarkers and inadequate therapy for a minority of patients that do not respond to standard pharmacotherapy. There is optimism that noninvasive brain stimulation may help to address these limitations. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two methods of noninvasive brain stimulation that modulate cortical excitability and brain network activity. TMS can be used diagnostically to probe cortical neurophysiology, while daily use of repetitive TMS or tDCS can induce long-lasting and potentially therapeutic changes in targeted networks. In this review we highlight research showing the potential diagnostic and therapeutic applications of TMS and tDCS in pediatric ADHD. We also discuss the safety and ethics of using these tools in the pediatric population. PMID:26661481

[Therapeutic efficacy and safety of repetitive Transcranial Magnetic Stimulation in depressions of the elderly: a review].

PubMed

Jalenques, I; Legrand, G; Vaille-Perret, E; Tourtauchaux, R; Galland, F

2010-06-01

During the past 15 years, therapeutic effects of repetitive Transcranial Magnetic Stimulation (rTMS) have been studied in psychiatric diseases, particularly in the treatment of depressive disorders. There are more and more data suggesting its efficacy in the treatment of depression in older patients. Thus, the authors found it useful to conduct an up-to-date review of studies that examined the efficacy and safety of rTMS to treat depressive disorders in the aged. After an exhaustive consultation of databases (Medline/PubMed and the Avery-George-Holtzheimer Database of rTMS Depression Studies), supplemented by a manual research, the authors retained studies evaluating the therapeutic efficacy of rTMS on depressive disorders in the aged. Fifteen studies were retained. Four open studies using high frequency rTMS, applied to the left dorsolateral prefrontal cortex (DLPFC), demonstrated a decrease in the mean Hamilton Depression Rating Scale (HDRS) scores; however, only a quarter of the aged patients studied experienced a significant remission of depression. Five parallel arm double-blind versus placebo studies concluded in contradicting results: two studies confirmed a significantly greater efficacy of rTMS compared to placebo, whereas three studies did not; but the sham procedure (positioning coil at 90 degrees from the scalp) was disputable in most studies. One study concluded in therapeutic efficacy by inhibiting the right DLPFC. Three controlled parallel arm studies compared rTMS and electroconvulsive-therapy (ECT); one study concluded in greater efficacy of ECT at end of treatment, but the number of ECT treatments depended on the patients' response, whereas a 15-day course of rTMS was systematically administered; additionally HDRS scores were similar in two groups of patients (rTMS and ECT) at 6 months. Lastly, three studies focused on aged patients with cerebrovascular disease. They showed the efficacy of rTMS, although older age and smaller frontal gray mater volumes were associated with a poorer response to rTMS. Thus, although some studies concluded contradicting results, literature data globally sustain an efficacy of rTMS for depression in the elderly. Several parameters might be associated with greater antidepressant efficacy (higher intensity pulses of rTMS of the left DLPFC; higher number of stimulations or higher number of rTMS sessions). Poorer responsiveness to rTMS may be related to several patients' factors including older age and smaller frontal gray matter volumes; lesions of the white matter pathways connecting the left DLPFC and the left anterior cingulate cortex might explain a poor response to rTMS. Literature data globally confirm that rTMS is safe and does not produce cognitive deficits, even among highly vulnerable patients with clinical evidence of cerebrovascular disease. Many questions remain concerning the optimal stimulation parameters, administration protocol, and privileged indications. Thus, the next rTMS studies should be carefully designed to clarify these questions. Copyright (c) 2009 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

The Role of the Right Dorsolateral Prefrontal Cortex in Phasic Alertness: Evidence from a Contingent Negative Variation and Repetitive Transcranial Magnetic Stimulation Study

PubMed Central

Mannarelli, Daniela; Pauletti, Caterina; Grippo, Antonello; Amantini, Aldo; Augugliaro, Vito; Currà, Antonio; Missori, Paolo; Locuratolo, Nicoletta; De Lucia, Maria C.; Rinalduzzi, Steno; Fattapposta, Francesco

2015-01-01

Phasic alertness represents the ability to increase response readiness to a target following an external warning stimulus. Specific networks in the frontal and parietal regions appear to be involved in the alert state. In this study, we examined the role of the right dorsolateral prefrontal cortex (DLPFC) during the attentional processing of a stimulus using a cued double-choice reaction time task. The evaluation of these processes was conducted by means of Event-Related Potentials (ERPs), in particular by using the Contingent Negative Variation (CNV), and repetitive 1-Hz Transcranial Magnetic Stimulation (rTMS). Transient virtual inhibition of the right DLPFC induced by real 1-Hz rTMS stimulation led to a significant decrease in total CNV and W1-CNV areas if compared with the basal and post-sham rTMS conditions. Reaction times (RTs) did not decrease after inhibitory rTMS, but they did improve after sham stimulation. These results suggest that the right DLPFC plays a crucial role in the genesis and maintenance of the alerting state and learning processes. PMID:26090234

Reduced surround inhibition in musicians.

PubMed

Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

2012-06-01

To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.

Effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) in patients with comorbid panic disorder and major depression.

PubMed

Kumar, Saurabh; Singh, Swarndeep; Parmar, Arpit; Verma, Rohit; Kumar, Nand

2018-05-01

To explore the role of dorsolateral prefrontal cortex (DLPFC) stimulation in the treatment of panic disorder with comorbid depression. The present study reports findings from retrospective analysis of 13 treatment-resistant patients diagnosed with comorbid panic disorder and depression, given 20 sessions of high-frequency transcranial magnetic stimulation (rTMS) over left-DLPFC over a period of 1 month. There was a significant reduction in both the panic and depressive symptom severity, assessed by applying Panic Disorder Severity Scale (PDSS) and Hamilton Depression Rating Scale (HDRS) at baseline and after 20 sessions of rTMS. There was a 38% and 40% reduction of PDSS and HDRS scores, respectively, in the sample. The changes in PDSS and HDRS scores were not significantly correlated (ρ = -0.103, p = 0.737). High-frequency rTMS delivered at left-DLPFC may have a potential role in treatment of comorbid panic disorder and depression. Future studies done on a larger sample in a controlled environment are required to establish its role.

Effect of tensile mean stress on fatigue behavior of single-crystal and directionally solidified superalloys

NASA Technical Reports Server (NTRS)

Kalluri, Sreeramesh; Mcgaw, Michael A.

1992-01-01

Two nickel base superalloys, single crystal PWA 1480 and directionally solidified MAR-M 246 + Hf, were studied in view of the potential usage of the former and usage of the latter as blade materials for the turbomachinery of the Space Shuttle main engine. The baseline zero mean stress (ZMS) fatigue life (FL) behavior of these superalloys was established, and then the effect of tensile mean stress (TMS) on their FL behavior was characterized. A stress range based FL prediction approach was used to characterize both the ZMS and TMS fatigue data. In the past, several researchers have developed methods to account for the detrimental effect of tensile mean stress on the FL for polycrystalline engineering alloys. These methods were applied to characterize the TMS fatigue data of single crystal PWA 1480 and directionally solidified MAR-M 246 + Hf and were found to be unsatisfactory. Therefore, a method of accounting for the TMS effect on FL, that is based on a technique proposed by Heidmann and Manson was developed to characterize the TMS fatigue data of these superalloys. Details of this method and its relationship to the conventionally used mean stress methods in FL prediction are discussed.

Analysing concurrent transcranial magnetic stimulation and electroencephalographic data: A review and introduction to the open-source TESA software.

PubMed

Rogasch, Nigel C; Sullivan, Caley; Thomson, Richard H; Rose, Nathan S; Bailey, Neil W; Fitzgerald, Paul B; Farzan, Faranak; Hernandez-Pavon, Julio C

2017-02-15

The concurrent use of transcranial magnetic stimulation with electroencephalography (TMS-EEG) is growing in popularity as a method for assessing various cortical properties such as excitability, oscillations and connectivity. However, this combination of methods is technically challenging, resulting in artifacts both during recording and following typical EEG analysis methods, which can distort the underlying neural signal. In this article, we review the causes of artifacts in EEG recordings resulting from TMS, as well as artifacts introduced during analysis (e.g. as the result of filtering over high-frequency, large amplitude artifacts). We then discuss methods for removing artifacts, and ways of designing pipelines to minimise analysis-related artifacts. Finally, we introduce the TMS-EEG signal analyser (TESA), an open-source extension for EEGLAB, which includes functions that are specific for TMS-EEG analysis, such as removing and interpolating the TMS pulse artifact, removing and minimising TMS-evoked muscle activity, and analysing TMS-evoked potentials. The aims of TESA are to provide users with easy access to current TMS-EEG analysis methods and to encourage direct comparisons of these methods and pipelines. It is hoped that providing open-source functions will aid in both improving and standardising analysis across the field of TMS-EEG research. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Optimal timing of pulse onset for language mapping with navigated repetitive transcranial magnetic stimulation.

PubMed

Krieg, Sandro M; Tarapore, Phiroz E; Picht, Thomas; Tanigawa, Noriko; Houde, John; Sollmann, Nico; Meyer, Bernhard; Vajkoczy, Peter; Berger, Mitchel S; Ringel, Florian; Nagarajan, Srikantan

2014-10-15

Within the primary motor cortex, navigated transcranial magnetic stimulation (nTMS) has been shown to yield maps strongly correlated with those generated by direct cortical stimulation (DCS). However, the stimulation parameters for repetitive nTMS (rTMS)-based language mapping are still being refined. For this purpose, the present study compares two rTMS protocols, which differ in the timing of pulse train onset relative to picture presentation onset during object naming. Results were the correlated with DCS language mapping during awake surgery. Thirty-two patients with left-sided perisylvian tumors were examined by rTMS prior to awake surgery. Twenty patients underwent rTMS pulse trains starting at 300 ms after picture presentation onset (delayed TMS), whereas another 12 patients received rTMS pulse trains starting at the picture presentation onset (ONSET TMS). These rTMS results were then evaluated for correlation with intraoperative DCS results as gold standard in terms of differential consistencies in receiver operating characteristics (ROC) statistics. Logistic regression analysis by protocols and brain regions were conducted. Within and around Broca's area, there was no difference in sensitivity (onset TMS: 100%, delayed TMS: 100%), negative predictive value (NPV) (onset TMS: 100%, delayed TMS: 100%), and positive predictive value (PPV) (onset TMS: 55%, delayed TMS: 54%) between the two protocols compared to DCS. However, specificity differed significantly (onset TMS: 67%, delayed TMS: 28%). In contrast, for posterior language regions, such as supramarginal gyrus, angular gyrus, and posterior superior temporal gyrus, early pulse train onset stimulation showed greater specificity (onset TMS: 92%, delayed TMS: 20%), NPV (onset TMS: 92%, delayed TMS: 57%) and PPV (onset TMS: 75%, delayed TMS: 30%) with comparable sensitivity (onset TMS: 75%, delayed TMS: 70%). Logistic regression analysis also confirmed the greater fit of the predictions by rTMS that had the pulse train onset coincident with the picture presentation onset when compared to the delayed stimulation. Analyses of differential disruption patterns of mapped cortical regions were further able to distinguish clusters of cortical regions standardly associated with semantic and pre-vocalization phonological networks proposed in various models of word production. Repetitive nTMS predictions by both protocols correlate well with DCS outcomes especially in Broca's region, particularly with regard to TMS negative predictions. With this study, we have demonstrated that rTMS stimulation onset coincident with picture presentation onset improves the accuracy of preoperative language maps, particularly within posterior language areas. Moreover, immediate and delayed pulse train onsets may have complementary disruption patterns that could differentially capture cortical regions causally necessary for semantic and pre-vocalization phonological networks. Published by Elsevier Inc.

Visual awareness suppression by pre-stimulus brain stimulation; a neural effect.

PubMed

Jacobs, Christianne; Goebel, Rainer; Sack, Alexander T

2012-01-02

Transcranial magnetic stimulation (TMS) has established the functional relevance of early visual cortex (EVC) for visual awareness with great temporal specificity non-invasively in conscious human volunteers. Many studies have found a suppressive effect when TMS was applied over EVC 80-100 ms after the onset of the visual stimulus (post-stimulus TMS time window). Yet, few studies found task performance to also suffer when TMS was applied even before visual stimulus presentation (pre-stimulus TMS time window). This pre-stimulus TMS effect, however, remains controversially debated and its origin had mainly been ascribed to TMS-induced eye-blinking artifacts. Here, we applied chronometric TMS over EVC during the execution of a visual discrimination task, covering an exhaustive range of visual stimulus-locked TMS time windows ranging from -80 pre-stimulus to 300 ms post-stimulus onset. Electrooculographical (EoG) recordings, sham TMS stimulation, and vertex TMS stimulation controlled for different types of non-neural TMS effects. Our findings clearly reveal TMS-induced masking effects for both pre- and post-stimulus time windows, and for both objective visual discrimination performance and subjective visibility. Importantly, all effects proved to be still present after post hoc removal of eye blink trials, suggesting a neural origin for the pre-stimulus TMS suppression effect on visual awareness. We speculate based on our data that TMS exerts its pre-stimulus effect via generation of a neural state which interacts with subsequent visual input. Copyright © 2011 Elsevier Inc. All rights reserved.

Neurocognitive Brain Response to Transient Impairment of Wernicke's Area

PubMed Central

Mason, Robert A.; Prat, Chantel S.; Just, Marcel Adam

2014-01-01

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure. PMID:23322403

Neurocognitive brain response to transient impairment of Wernicke's area.

PubMed

Mason, Robert A; Prat, Chantel S; Just, Marcel Adam

2014-06-01

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure.

Vegetative versus minimally conscious states: a study using TMS-EEG, sensory and event-related potentials.

PubMed

Ragazzoni, Aldo; Pirulli, Cornelia; Veniero, Domenica; Feurra, Matteo; Cincotta, Massimo; Giovannelli, Fabio; Chiaramonti, Roberta; Lino, Mario; Rossi, Simone; Miniussi, Carlo

2013-01-01

Differential diagnoses between vegetative and minimally conscious states (VS and MCS, respectively) are frequently incorrect. Hence, further research is necessary to improve the diagnostic accuracy at the bedside. The main neuropathological feature of VS is the diffuse damage of cortical and subcortical connections. Starting with this premise, we used electroencephalography (EEG) recordings to evaluate the cortical reactivity and effective connectivity during transcranial magnetic stimulation (TMS) in chronic VS or MCS patients. Moreover, the TMS-EEG data were compared with the results from standard somatosensory-evoked potentials (SEPs) and event-related potentials (ERPs). Thirteen patients with chronic consciousness disorders were examined at their bedsides. A group of healthy volunteers served as the control group. The amplitudes (reactivity) and scalp distributions (connectivity) of the cortical potentials evoked by TMS (TEPs) of the primary motor cortex were measured. Short-latency median nerve SEPs and auditory ERPs were also recorded. Reproducible TEPs were present in all control subjects in both the ipsilateral and the contralateral hemispheres relative to the site of the TMS. The amplitudes of the ipsilateral and contralateral TEPs were reduced in four of the five MCS patients, and the TEPs were bilaterally absent in one MCS patient. Among the VS patients, five did not manifest ipsilateral or contralateral TEPs, and three of the patients exhibited only ipsilateral TEPs with reduced amplitudes. The SEPs were altered in five VS and two MCS patients but did not correlate with the clinical diagnosis. The ERPs were impaired in all patients and did not correlate with the clinical diagnosis. These TEP results suggest that cortical reactivity and connectivity are severely impaired in all VS patients, whereas in most MCS patients, the TEPs are preserved but with abnormal features. Therefore, TEPs may add valuable information to the current clinical and neurophysiological assessment of chronic consciousness disorders.

Vegetative versus Minimally Conscious States: A Study Using TMS-EEG, Sensory and Event-Related Potentials

PubMed Central

Ragazzoni, Aldo; Pirulli, Cornelia; Veniero, Domenica; Feurra, Matteo; Cincotta, Massimo; Giovannelli, Fabio; Chiaramonti, Roberta; Lino, Mario; Rossi, Simone; Miniussi, Carlo

2013-01-01

Differential diagnoses between vegetative and minimally conscious states (VS and MCS, respectively) are frequently incorrect. Hence, further research is necessary to improve the diagnostic accuracy at the bedside. The main neuropathological feature of VS is the diffuse damage of cortical and subcortical connections. Starting with this premise, we used electroencephalography (EEG) recordings to evaluate the cortical reactivity and effective connectivity during transcranial magnetic stimulation (TMS) in chronic VS or MCS patients. Moreover, the TMS-EEG data were compared with the results from standard somatosensory-evoked potentials (SEPs) and event-related potentials (ERPs). Thirteen patients with chronic consciousness disorders were examined at their bedsides. A group of healthy volunteers served as the control group. The amplitudes (reactivity) and scalp distributions (connectivity) of the cortical potentials evoked by TMS (TEPs) of the primary motor cortex were measured. Short-latency median nerve SEPs and auditory ERPs were also recorded. Reproducible TEPs were present in all control subjects in both the ipsilateral and the contralateral hemispheres relative to the site of the TMS. The amplitudes of the ipsilateral and contralateral TEPs were reduced in four of the five MCS patients, and the TEPs were bilaterally absent in one MCS patient. Among the VS patients, five did not manifest ipsilateral or contralateral TEPs, and three of the patients exhibited only ipsilateral TEPs with reduced amplitudes. The SEPs were altered in five VS and two MCS patients but did not correlate with the clinical diagnosis. The ERPs were impaired in all patients and did not correlate with the clinical diagnosis. These TEP results suggest that cortical reactivity and connectivity are severely impaired in all VS patients, whereas in most MCS patients, the TEPs are preserved but with abnormal features. Therefore, TEPs may add valuable information to the current clinical and neurophysiological assessment of chronic consciousness disorders. PMID:23460826

rTMS strategies for the study and treatment of schizophrenia: a review

PubMed Central

Stanford, Arielle D.; Sharif, Zafar; Corcoran, Cheryl; Urban, Nina; Malaspina, Dolores; Lisanby, Sarah H.

2010-01-01

Transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) have been used increasingly over the past few years to study both the pathophysiology of schizophrenia as well as the utility of focal neuromodulation as a novel treatment for schizophrenia. rTMS treatment studies to date have explored its effect on both positive and negative symptoms by targeting cortical regions thought to underlie these symptom clusters. Studies on auditory hallucinations have been largely positive, while efficacy for negative symptoms is equivocal. A better understanding of the functional abnormalities that accompany symptoms may facilitate the development of rTMS as a treatment modality. Furthermore, schizophrenia patients appear to have abnormal cortical inhibition, consistent with GABA and dopamine abnormalities in schizophrenia. The effect of TMS on GABA and dopamine neurotransmission has not been clearly delineated. Given the variability in cortical response to rTMS in schizophrenia, methods to optimize dosage are essential. Consideration of these factors among others may broaden the scope of utility of TMS for schizophrenia as well as enhance its efficacy. PMID:18241358

Age-related differences in short- and long-interval intracortical inhibition in a human hand muscle.

PubMed

Opie, George M; Semmler, John G

2014-01-01

Effects of age on the assessment of intracortical inhibition with paired-pulse transcranial magnetic stimulation (TMS) have been variable, which may be due to between-study differences in test TMS intensity and test motor evoked potential (MEP) amplitude. To investigate age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) across a range of test TMS intensities and test MEP amplitudes. In 22 young and 18 older subjects, SICI and LICI were recorded at a range of test TMS intensities (110%-150% of motor threshold) while the first dorsal interosseous (FDI) muscle was at rest, or producing a precision grip of the index finger and thumb. Data were subsequently compared according to the amplitude of the MEP produced by the test alone TMS. When pooled across all test TMS intensities, SICI in resting muscle and LICI in active muscle were similar in young and older adults, whereas SICI in active muscle and LICI in resting muscle were reduced in older adults. Regrouping data based on test MEP amplitude demonstrated similar effects of age for SICI and LICI in resting muscle, whereas more subtle differences between age groups were revealed for SICI and LICI in active muscle. Advancing age influences GABA-mediated intracortical inhibition, but the outcome is dependent on the experimental conditions. Age-related differences in SICI and LICI were influenced by test TMS intensity and test MEP amplitude, suggesting that these are important considerations when assessing intracortical inhibition in older adults, particularly in an active muscle. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study

PubMed Central

Albuquerque, Plínio Luna; Campêlo, Mayara; Mendonça, Thyciane; Fontes, Luís Augusto Mendes; Brito, Rodrigo de Mattos

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP’s amplitude and NFR’s area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR’s area. High-frequency rTMS increased MEP’s amplitude and NFR’s area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes. PMID:29596524

Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study.

PubMed

Albuquerque, Plínio Luna; Campêlo, Mayara; Mendonça, Thyciane; Fontes, Luís Augusto Mendes; Brito, Rodrigo de Mattos; Monte-Silva, Katia

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP's amplitude and NFR's area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR's area. High-frequency rTMS increased MEP's amplitude and NFR's area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes.

Comparative efficacy and acceptability of electroconvulsive therapy versus repetitive transcranial magnetic stimulation for major depression: A systematic review and multiple-treatments meta-analysis.

PubMed

Chen, Jian-Jun; Zhao, Li-Bo; Liu, Yi-Yun; Fan, Song-Hua; Xie, Peng

2017-03-01

The effects of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS) on major depressive disorder (MDD) have not been adequately addressed by previous studies. Here, a multiple-treatments meta-analysis, which incorporates evidence from direct and indirect comparisons from a network of trials, was performed to assess the efficacy and acceptability of these four treatment modalities on MDD. The literature was searched for randomized controlled trials (RCTs) on ECT, bilateral rTMS, and unilateral rTMS for treating MDD up to May 2016. The main outcome measures were response and drop-out rates. Data were obtained from 25 studies consisting of 1288 individuals with MDD. ECT was non-significantly more efficacious than B-rTMS, R-rTMS, and L-rTMS. Left prefrontal rTMS was non -significantly less efficacious than all other treatment modalities. In terms of acceptability, R-rTMS was non-significantly better tolerated than ECT, B-rTMS, and L-rTMS. ECT was the most efficacious treatment with the cumulative probabilities of being the most efficacious treatment being: ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best-tolerated treatment with the cumulative probabilities of being the best-tolerated treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%). Coherence analysis detected no statistically significant incoherence in any comparisons of direct with indirect evidence for the response rate and drop-out rate. ECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability. Copyright © 2016 Elsevier B.V. All rights reserved.

Default Mode Network Mechanisms of Transcranial Magnetic Stimulation in Depression

PubMed Central

Liston, Conor; Chen, Ashley C.; Zebley, Benjamin D.; Drysdale, Andrew T.; Gordon, Rebecca; Leuchter, Bruce; Voss, Henning U.; Casey, B.J.; Etkin, Amit; Dubin, Marc J.

2014-01-01

Background Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks—the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)—are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response. Methods We used resting state functional magnetic resonance imaging (rs-fMRI) to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a five-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared to a cohort of 35 healthy controls. Results Prior to treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. TMS normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. TMS also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement. Conclusions TMS selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response. PMID:24629537

Opposite optimal current flow directions for induction of neuroplasticity and excitation threshold in the human motor cortex.

PubMed

Sommer, Martin; Norden, Christoph; Schmack, Lars; Rothkegel, Holger; Lang, Nicolas; Paulus, Walter

2013-05-01

Directional sensitivity is relevant for the excitability threshold of the human primary motor cortex, but its importance for externally induced plasticity is unknown. To study the influence of current direction on two paradigms inducing neuroplasticity by repetitive transcranial magnetic stimulation (rTMS). We studied short-lasting after-effects induced in the human primary motor cortex of 8 healthy subjects, using 5 Hz rTMS applied in six blocks of 200 pulses each, at 90% active motor threshold. We controlled for intensity, frequency, waveform and spinal effects. Only biphasic pulses with the effective component delivered in an anterioposterior direction (henceforth posteriorly directed) in the brain yielded an increase of motor-evoked potential (MEP) amplitudes outlasting rTMS. MEP latencies and F-wave amplitudes remained unchanged. Biphasic pulses directed posteroanterior (i.e. anteriorly) were ineffective, as were monophasic pulses from either direction. A 1 Hz study in a group of 12 healthy subjects confirmed facilitation after posteriorly directed biphasic pulses only. The anisotropy of the human primary motor cortex is relevant for induction of plasticity by subtreshold rTMS, with a current flow opposite to that providing lowest excitability thresholds. This is consistent with the idea of TMS primarily targeting cortical columns of the phylogenetically new M1 in the anterior bank of the central sulcus. For these, anteriorly directed currents are soma-depolarizing, therefore optimal for low thresholds, whereas posteriorly directed currents are soma-hyperpolarizing, likely dendrite-depolarizing and bested suited for induction of plasticity. Our findings should help focus and enhance rTMS effects in experimental and clinical settings. Copyright © 2013 Elsevier Inc. All rights reserved.

Transcranial magnetic stimulation of the brain: guidelines for pain treatment research

PubMed Central

Klein, Max M.; Treister, Roi; Raij, Tommi; Pascual-Leone, Alvaro; Park, Lawrence; Nurmikko, Turo; Lenz, Fred; Lefaucheur, Jean-Pascal; Lang, Magdalena; Hallett, Mark; Fox, Michael; Cudkowicz, Merit; Costello, Ann; Carr, Daniel B.; Ayache, Samar S.; Oaklander, Anne Louise

2015-01-01

Abstract Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after initiation with prespecified statistical analyses. Multigroup collaborations or registry studies may be needed for pivotal trials. PMID:25919472

ARTIST: A fully automated artifact rejection algorithm for single-pulse TMS-EEG data.

PubMed

Wu, Wei; Keller, Corey J; Rogasch, Nigel C; Longwell, Parker; Shpigel, Emmanuel; Rolle, Camarin E; Etkin, Amit

2018-04-01

Concurrent single-pulse TMS-EEG (spTMS-EEG) is an emerging noninvasive tool for probing causal brain dynamics in humans. However, in addition to the common artifacts in standard EEG data, spTMS-EEG data suffer from enormous stimulation-induced artifacts, posing significant challenges to the extraction of neural information. Typically, neural signals are analyzed after a manual time-intensive and often subjective process of artifact rejection. Here we describe a fully automated algorithm for spTMS-EEG artifact rejection. A key step of this algorithm is to decompose the spTMS-EEG data into statistically independent components (ICs), and then train a pattern classifier to automatically identify artifact components based on knowledge of the spatio-temporal profile of both neural and artefactual activities. The autocleaned and hand-cleaned data yield qualitatively similar group evoked potential waveforms. The algorithm achieves a 95% IC classification accuracy referenced to expert artifact rejection performance, and does so across a large number of spTMS-EEG data sets (n = 90 stimulation sites), retains high accuracy across stimulation sites/subjects/populations/montages, and outperforms current automated algorithms. Moreover, the algorithm was superior to the artifact rejection performance of relatively novice individuals, who would be the likely users of spTMS-EEG as the technique becomes more broadly disseminated. In summary, our algorithm provides an automated, fast, objective, and accurate method for cleaning spTMS-EEG data, which can increase the utility of TMS-EEG in both clinical and basic neuroscience settings. © 2018 Wiley Periodicals, Inc.

Not all transmembrane helices are born equal: Towards the extension of the sequence homology concept to membrane proteins

PubMed Central

2011-01-01

Background Sequence homology considerations widely used to transfer functional annotation to uncharacterized protein sequences require special precautions in the case of non-globular sequence segments including membrane-spanning stretches composed of non-polar residues. Simple, quantitative criteria are desirable for identifying transmembrane helices (TMs) that must be included into or should be excluded from start sequence segments in similarity searches aimed at finding distant homologues. Results We found that there are two types of TMs in membrane-associated proteins. On the one hand, there are so-called simple TMs with elevated hydrophobicity, low sequence complexity and extraordinary enrichment in long aliphatic residues. They merely serve as membrane-anchoring device. In contrast, so-called complex TMs have lower hydrophobicity, higher sequence complexity and some functional residues. These TMs have additional roles besides membrane anchoring such as intra-membrane complex formation, ligand binding or a catalytic role. Simple and complex TMs can occur both in single- and multi-membrane-spanning proteins essentially in any type of topology. Whereas simple TMs have the potential to confuse searches for sequence homologues and to generate unrelated hits with seemingly convincing statistical significance, complex TMs contain essential evolutionary information. Conclusion For extending the homology concept onto membrane proteins, we provide a necessary quantitative criterion to distinguish simple TMs (and a sufficient criterion for complex TMs) in query sequences prior to their usage in homology searches based on assessment of hydrophobicity and sequence complexity of the TM sequence segments. Reviewers This article was reviewed by Shamil Sunyaev, L. Aravind and Arcady Mushegian. PMID:22024092

Development of Commercial Thermo-sensitive Genic Male Sterile Rice Accelerates Hybrid Rice Breeding Using the CRISPR/Cas9-mediated TMS5 Editing System

PubMed Central

Zhou, Hai; He, Ming; Li, Jing; Chen, Liang; Huang, Zhifeng; Zheng, Shaoyan; Zhu, Liya; Ni, Erdong; Jiang, Dagang; Zhao, Bingran; Zhuang, Chuxiong

2016-01-01

Hybrid rice breeding offers an important strategy to improve rice production, in which the cultivation of a male sterile line is the key to the success of cross-breeding. CRISPR/Cas9 systems have been widely used in target-site genome editing, whereas their application for crop genetic improvement has been rarely reported. Here, using the CRISPR/Cas9 system, we induced specific mutations in TMS5, which is the most widely applied thermo-sensitive genic male sterility (TGMS) gene in China, and developed new “transgene clean” TGMS lines. We designed 10 target sites in the coding region of TMS5 for targeted mutagenesis using the CRISPR/Cas9 system and assessed the potential rates of on- and off-target effects. Finally, we established the most efficient construct, the TMS5ab construct, for breeding potentially applicable “transgene clean” TGMS lines. We also discussed factors that affect the editing efficiency according to the characteristics of different target sequences. Notably, using the TMS5ab construct, we developed 11 new “transgene clean” TGMS lines with potential applications in hybrid breeding within only one year in both rice subspecies. The application of our system not only significantly accelerates the breeding of sterile lines but also facilitates the exploitation of heterosis. PMID:27874087

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

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Odagaki, Masato; Hiwaki, Osamu

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

Reliability of lower limb transcranial magnetic stimulation outcomes in the ipsi- and contralesional hemispheres of adults with chronic stroke.

PubMed

Beaulieu, Louis-David; Massé-Alarie, Hugo; Ribot-Ciscar, Edith; Schneider, Cyril

2017-07-01

To investigate the ability of transcranial magnetic stimulation (TMS) outcomes in the chronic stroke population to (i) track individual plastic changes and (ii) detect differences between individuals. To this end, intrarater "test-retest" reliability (relative and absolute) was tested for the ipsilesional and contralesional hemispheres. Thirteen participants with a unilateral stroke (≥6months ago) and sensorimotor impairments were enrolled. Single and paired-pulse TMS outcomes were obtained from the primary motor cortex (M1) representation of the tibialis anterior muscle in both hemispheres and at two sessions separated by one week. The standard error of the measurement (SEM eas ), minimal detectable change (MDC) and intraclass correlation coefficient (ICC) were studied. Active motor threshold and latency of motor evoked potentials provided the lowest SEM eas and highest ICCs for both ipsi- and contralesional hemispheres. However, MDC were generally large, thus questioning the use of TMS outcomes to track individual plastic changes of M1. Our study provided supporting evidence of good to excellent intrarater reliability for a few TMS outcomes and proposed recommendations on the interpretation and the use of that knowledge in future work. Psychometric properties of TMS measures should be further addressed in order to better understand how to refine their use in clinical settings. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation Combined with Task-Oriented Mirror Therapy Training on Hand Rehabilitation of Acute Stroke Patients.

PubMed

Kim, Jinhong; Yim, Jongeun

2018-02-06

BACKGROUND Impairments of hand function make it difficult to perform daily life activities and to return to work. The aim of this study was to investigate the effect of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with task-oriented mirror therapy (TOMT) on hand rehabilitation in acute stroke patients. MATERIAL AND METHODS Twenty subacute stroke patients in the initial stages (<3 months) participated in the study. Subjects were allocated to 2 groups: the experimental group received HF-rTMS + TOMT and the control group received HF-rTMS. TOMT training was conducted in 10 sessions over 2 weeks for 30 min. rTMS was applied at a 20 Hz frequency over the hand motor area in the cortex of the affected hemisphere for 15 min. Outcomes, including motor-evoked potential (MEP), pinch grip, hand grip, and box and block test, were measured before and after training. RESULTS Significant improvements in the MEP and hand function variables were observed in both groups (p<0.05). In particular, hand functions (pinch grip and box and block test) were significantly different between the 2 groups (p<0.05). CONCLUSIONS HF-rTMS combined with TOMT had a positive effect on hand function and can be used for the rehabilitation of precise hand movements in acute stroke patients.

Improved Discrimination of Visual Stimuli Following Repetitive Transcranial Magnetic Stimulation

PubMed Central

Waterston, Michael L.; Pack, Christopher C.

2010-01-01

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. PMID:20442776

Repetitive transcranial magnetic stimulation induces oscillatory power changes in chronic tinnitus

PubMed Central

Schecklmann, Martin; Lehner, Astrid; Gollmitzer, Judith; Schmidt, Eldrid; Schlee, Winfried; Langguth, Berthold

2015-01-01

Chronic tinnitus is associated with neuroplastic changes in auditory and non-auditory cortical areas. About 10 years ago, repetitive transcranial magnetic stimulation (rTMS) of auditory and prefrontal cortex was introduced as potential treatment for tinnitus. The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity). Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63-channel electroencephalography (EEG) system. Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1 Hz and with an intensity of 60% stimulator output. Stimulation of central parietal cortex with 6-fold reduced intensity (inverted passive-cooled coil) served as sham condition. Before and after each rTMS protocol 5 min of resting state EEG were recorded. The order of rTMS protocols was randomized over two sessions with 1 week interval in between. Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. No changes or increases were observed in the control group. Only non-systematic changes in tinnitus loudness were induced by single sessions of rTMS. This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. The observed effects can be interpreted within the thalamocortical dysrhythmia model assuming that slow waves represent processes of deafferentiation and that high frequencies might be indicators for tinnitus loudness. Moreover our findings confirm the role of the left temporal and the right frontal areas as relevant hubs in tinnitus related neuronal network. Our results underscore the value of combined TMS-EEG measurements for investigating disease related changes in neuroplasticity. PMID:26557055

Adaptability and reproducibility of a memory disruption rTMS protocol in the PharmaCog IMI European project.

PubMed

Martin-Trias, Pablo; Lanteaume, Laura; Solana, Elisabeth; Cassé-Perrot, Catherine; Fernández-Cabello, Sara; Babiloni, Claudio; Marzano, Nicola; Junqué, Carme; Rossini, Paolo Maria; Micallef, Joëlle; Truillet, Romain; Charles, Estelle; Jouve, Elisabeth; Bordet, Régis; Santamaria, Joan; Jovicich, Jorge; Rossi, Simone; Pascual-Leone, Alvaro; Blin, Olivier; Richardson, Jill; Bartrés-Faz, David

2018-06-19

Transcranial magnetic stimulation (TMS) can interfere with cognitive processes, such as transiently impairing memory. As part of a multi-center European project, we investigated the adaptability and reproducibility of a previously published TMS memory interfering protocol in two centers using EEG or fMRI scenarios. Participants were invited to attend three experimental sessions on different days, with sham repetitive TMS (rTMS) applied on day 1 and real rTMS on days 2 and 3. Sixty-eight healthy young men were included. On each experimental day, volunteers were instructed to remember visual pictures while receiving neuronavigated rTMS trains (20 Hz, 900 ms) during picture encoding at the left dorsolateral prefrontal cortex (L-DLPFC) and the vertex. Mixed ANOVA model analyses were performed. rTMS to the L-DLPFC significantly disrupted recognition memory on experimental day 2. No differences were found between centers or between fMRI and EEG recordings. Subjects with lower baseline memory performances were more susceptible to TMS disruption. No stability of TMS-induced memory interference could be demonstrated on day 3. Our data suggests that adapted cognitive rTMS protocols can be implemented in multi-center studies incorporating standardized experimental procedures. However, our center and modality effects analyses lacked sufficient statistical power, hence highlighting the need to conduct further studies with larger samples. In addition, inter and intra-subject variability in response to TMS might limit its application in crossover or longitudinal studies.

Functional magnetic resonance imaging and transcranial magnetic stimulation: effects of motor imagery, movement and coil orientation.

PubMed

Niyazov, D M; Butler, A J; Kadah, Y M; Epstein, C M; Hu, X P

2005-07-01

To compare fMRI activations during movement and motor imagery to corresponding motor evoked potential (MEP) maps obtained with the TMS coil in three different orientations. fMRI activations during executed (EM) and imagined (IM) movements of the index finger were compared to MEP maps of the first dorsal interosseus (FDI) muscle obtained with the TMS coil in anterior, posterior and lateral handle positions. To ensure spatial registration of fMRI and MEP maps, a special grid was used in both experiments. No statistically significant difference was found between the TMS centers of gravity (TMS CoG) obtained with the three coil orientations. There was a significant difference between fMRI centers of gravity during IMs (IM CoG) and EMs (EM CoG), with IM CoGs localized on average 10.3mm anterior to those of EMs in the precentral gyrus. Most importantly, the IM CoGs closely matched cortical projections of the TMS CoGs while the EM CoGs were on average 9.5mm posterior to the projected TMS CoGs. TMS motor maps are more congruent with fMRI activations during motor imagery than those during EMs. These findings are not significantly affected by changing orientation of the TMS coil. Our results suggest that the discrepancy between fMRI and TMS motor maps may be largely due to involvement of the somatosensory component in the EM task.

Group-level variations in motor representation areas of thenar and anterior tibial muscles: Navigated Transcranial Magnetic Stimulation Study.

PubMed

Niskanen, Eini; Julkunen, Petro; Säisänen, Laura; Vanninen, Ritva; Karjalainen, Pasi; Könönen, Mervi

2010-08-01

Navigated transcranial magnetic stimulation (TMS) can be used to stimulate functional cortical areas at precise anatomical location to induce measurable responses. The stimulation has commonly been focused on anatomically predefined motor areas: TMS of that area elicits a measurable muscle response, the motor evoked potential. In clinical pathologies, however, the well-known homunculus somatotopy theory may not be straightforward, and the representation area of the muscle is not fixed. Traditionally, the anatomical locations of TMS stimulations have not been reported at the group level in standard space. This study describes a methodology for group-level analysis by investigating the normal representation areas of thenar and anterior tibial muscle in the primary motor cortex. The optimal representation area for these muscles was mapped in 59 healthy right-handed subjects using navigated TMS. The coordinates of the optimal stimulation sites were then normalized into standard space to determine the representation areas of these muscles at the group-level in healthy subjects. Furthermore, 95% confidence interval ellipsoids were fitted into the optimal stimulation site clusters to define the variation between subjects in optimal stimulation sites. The variation was found to be highest in the anteroposterior direction along the superior margin of the precentral gyrus. These results provide important normative information for clinical studies assessing changes in the functional cortical areas because of plasticity of the brain. Furthermore, it is proposed that the presented methodology to study TMS locations at the group level on standard space will be a suitable tool for research purposes in population studies. 2010 Wiley-Liss, Inc.

Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder.

PubMed

Assaf, Michal; Rabany, Liron; Zertuche, Luis; Bragdon, Laura; Tolin, David; Goethe, John; Diefenbach, Gretchen

2018-06-21

Recent evidence suggests that repetitive transcranial magnetic stimulation (rTMS) might be effective in treating generalized anxiety disorder (GAD). Cognitive models of GAD highlight the role of intolerance of uncertainty (IU) in precipitating and maintaining worry, and it has been hypothesized that patients with GAD exhibit decision-making deficits under uncertain conditions. Improving understanding of the neural mechanisms underlying cognitive deficits associated with IU may lead to the identification of novel rTMS treatment targets and optimization of treatment parameters. The current report describes two interrelated studies designed to identify and verify a potential neural target for rTMS treatment of GAD. Study I explored the integrity of prefrontal cortex (PFC) and amygdala neural networks, which underlie decision making under conditions of uncertainty, in GAD. Individuals diagnosed with GAD (n = 31) and healthy controls (n = 20) completed a functional magnetic resonance imaging (fMRI) gambling task that manipulated uncertainty using high versus low error rates. In a subsequent randomized-controlled trial (Study II), a subset of the GAD sample (n = 16) completed the fMRI gambling task again after 30 sessions of active versus sham rTMS (1 Hz, right dorsolateral prefrontal cortex) to investigate the modulation of functional networks and symptoms. In Study I, participants with GAD demonstrated impairments in PFC-PFC and PFC-amygdala functional connectivity (FC) mostly during the high uncertainty condition. In Study II, one region of interest pair, dorsal anterior cingulate (ACC) - subgenual ACC, showed "normalization" of FC following active, but not sham, rTMS, and neural changes were associated with improvement in worry symptoms. These results outline a possible treatment mechanism of rTMS in GAD, and pave the way for future studies of treatment optimization. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Transient suppression of seizures by repetitive transcranial magnetic stimulation in a case of Rasmussen's encephalitis.

PubMed

Rotenberg, Alexander; Depositario-Cabacar, Dewi; Bae, Erica Hyunji; Harini, Chellamani; Pascual-Leone, Alvaro; Takeoka, Masanori

2008-07-01

Repetitive transcranial magnetic stimulation (rTMS) has been applied with variable success to terminate the seizures of epilepsia partialis continua. The rationale for using this technique to suppress ongoing seizures is the capacity of rTMS to interrupt ongoing neuronal activity, and to produce a lasting decrease in cortical excitability with low-frequency (1 Hz) stimulation. We report a case of epilepsia partialis continua in a child with Rasmussen's encephalitis, in whom seizures were transiently suppressed by 1-Hz rTMS delivered in nine daily 30-minute sessions. In this case, total ictal time was significantly reduced during stimulation, but the daily baseline seizure rate remained unchanged. Notably, the detection and quantification of this short-lived improvement were enabled by recording EEG continuously during the rTMS session. Thus, we present this case to illustrate a potential utility of combined continuous EEG recording and rTMS in seizure treatment.

Evaluating the Role of the Dorsolateral Prefrontal Cortex and Posterior Parietal Cortex in Memory-Guided Attention With Repetitive Transcranial Magnetic Stimulation.

PubMed

Wang, Min; Yang, Ping; Wan, Chaoyang; Jin, Zhenlan; Zhang, Junjun; Li, Ling

2018-01-01

The contents of working memory (WM) can affect the subsequent visual search performance, resulting in either beneficial or cost effects, when the visual search target is included in or spatially dissociated from the memorized contents, respectively. The right dorsolateral prefrontal cortex (rDLPFC) and the right posterior parietal cortex (rPPC) have been suggested to be associated with the congruence/incongruence effects of the WM content and the visual search target. Thus, in the present study, we investigated the role of the dorsolateral prefrontal cortex and the PPC in controlling the interaction between WM and attention during a visual search, using repetitive transcranial magnetic stimulation (rTMS). Subjects maintained a color in WM while performing a search task. The color cue contained the target (valid), the distractor (invalid) or did not reappear in the search display (neutral). Concurrent stimulation with the search onset showed that relative to rTMS over the vertex, rTMS over rPPC and rDLPFC further decreased the search reaction time, when the memory cue contained the search target. The results suggest that the rDLPFC and the rPPC are critical for controlling WM biases in human visual attention.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex reduces resting-state insula activity and modulates functional connectivity of the orbitofrontal cortex in cigarette smokers.

PubMed

Li, Xingbao; Du, Lian; Sahlem, Gregory L; Badran, Bashar W; Henderson, Scott; George, Mark S

2017-05-01

Previous studies reported that repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving and decrease cigarette consumption in smokers. The mechanism of this effect however, remains unclear. We used resting-state functional magnetic resonance imaging (rsfMRI) to test the effect of rTMS in non-treatment seeking smokers. We used a single blinded, sham-controlled, randomized counterbalanced crossover design where participants underwent two visits separated by at least 1 week. Participants received active rTMS over the left dorsolateral prefrontal cortex (DLPFC) during one of their visits, and sham rTMS during their other visit. They had two rsFMRI scans before and after each rTMS session. We used the same rTMS stimulation parameters as in a previous study (10Hz, 5s-on, 10s-off, 100% resting motor threshold, 3000 pulses). Ten non-treatment-seeking, nicotine-dependent, cigarette smokers (6 women, an average age of 39.72 and an average cigarette per day of 17.30) finished the study. rsFMRI results demonstrate that as compared to a single session of sham rTMS, a single session of active rTMS inhibits brain activity in the right insula and thalamus in fractional amplitude of low frequency fluctuation (fALFF). For intrinsic brain connectivity comparisons, active TMS resulted in significantly decreased connectivity from the site of rTMS to the left orbitomedial prefrontal cortex. This data suggests that one session of rTMS can reduce activity in the right insula and right thalamus as measured by fALFF. The data also demonstrates that rTMS can reduce rsFC between the left DLPFC and the medial orbitofrontal cortex. Copyright © 2017 Elsevier B.V. All rights reserved.

Solving the Orientation Specific Constraints in Transcranial Magnetic Stimulation by Rotating Fields

PubMed Central

Neef, Nicole E.; Agudelo-Toro, Andres; Rakhmilevitch, David; Paulus, Walter; Moses, Elisha

2014-01-01

Transcranial Magnetic Stimulation (TMS) is a promising technology for both neurology and psychiatry. Positive treatment outcome has been reported, for instance in double blind, multi-center studies on depression. Nonetheless, the application of TMS towards studying and treating brain disorders is still limited by inter-subject variability and lack of model systems accessible to TMS. The latter are required to obtain a deeper understanding of the biophysical foundations of TMS so that the stimulus protocol can be optimized for maximal brain response, while inter-subject variability hinders precise and reliable delivery of stimuli across subjects. Recent studies showed that both of these limitations are in part due to the angular sensitivity of TMS. Thus, a technique that would eradicate the need for precise angular orientation of the coil would improve both the inter-subject reliability of TMS and its effectiveness in model systems. We show here how rotation of the stimulating field relieves the angular sensitivity of TMS and provides improvements in both issues. Field rotation is attained by superposing the fields of two coils positioned orthogonal to each other and operated with a relative phase shift in time. Rotating field TMS (rfTMS) efficiently stimulates both cultured hippocampal networks and rat motor cortex, two neuronal systems that are notoriously difficult to excite magnetically. This opens the possibility of pharmacological and invasive TMS experiments in these model systems. Application of rfTMS to human subjects overcomes the orientation dependence of standard TMS. Thus, rfTMS yields optimal targeting of brain regions where correct orientation cannot be determined (e.g., via motor feedback) and will enable stimulation in brain regions where a preferred axonal orientation does not exist. PMID:24505266

On the feasibility of concurrent human TMS-EEG-fMRI measurements

PubMed Central

Reithler, Joel; Schuhmann, Teresa; de Graaf, Tom; Uludağ, Kâmil; Goebel, Rainer; Sack, Alexander T.

2013-01-01

Simultaneously combining the complementary assets of EEG, functional MRI (fMRI), and transcranial magnetic stimulation (TMS) within one experimental session provides synergetic results, offering insights into brain function that go beyond the scope of each method when used in isolation. The steady increase of concurrent EEG-fMRI, TMS-EEG, and TMS-fMRI studies further underlines the added value of such multimodal imaging approaches. Whereas concurrent EEG-fMRI enables monitoring of brain-wide network dynamics with high temporal and spatial resolution, the combination with TMS provides insights in causal interactions within these networks. Thus the simultaneous use of all three methods would allow studying fast, spatially accurate, and distributed causal interactions in the perturbed system and its functional relevance for intact behavior. Concurrent EEG-fMRI, TMS-EEG, and TMS-fMRI experiments are already technically challenging, and the three-way combination of TMS-EEG-fMRI might yield additional difficulties in terms of hardware strain or signal quality. The present study explored the feasibility of concurrent TMS-EEG-fMRI studies by performing safety and quality assurance tests based on phantom and human data combining existing commercially available hardware. Results revealed that combined TMS-EEG-fMRI measurements were technically feasible, safe in terms of induced temperature changes, allowed functional MRI acquisition with comparable image quality as during concurrent EEG-fMRI or TMS-fMRI, and provided artifact-free EEG before and from 300 ms after TMS pulse application. Based on these empirical findings, we discuss the conceptual benefits of this novel complementary approach to investigate the working human brain and list a number of precautions and caveats to be heeded when setting up such multimodal imaging facilities with current hardware. PMID:23221407

Ethanol modulates cortical activity: direct evidence with combined TMS and EEG.

PubMed

Kähkönen, S; Kesäniemi, M; Nikouline, V V; Karhu, J; Ollikainen, M; Holi, M; Ilmoniemi, R J

2001-08-01

The motor cortex of 10 healthy subjects was stimulated by transcranial magnetic stimulation (TMS) before and after ethanol challenge (0.8 g/kg resulting in blood concentration of 0.77 +/- 0.14 ml/liter). The electrical brain activity resulting from the brief electromagnetic pulse was recorded with high-resolution electroencephalography (EEG) and located using inversion algorithms. Focal magnetic pulses to the left motor cortex were delivered with a figure-of-eight coil at the random interstimulus interval of 1.5-2.5 s. The stimulation intensity was adjusted to the motor threshold of abductor digiti minimi. Two conditions before and after ethanol ingestion (30 min) were applied: (1) real TMS, with the coil pressed against the scalp; and (2) control condition, with the coil separated from the scalp by a 2-cm-thick piece of plastic. A separate EMG control recording of one subject during TMS was made with two bipolar platinum needle electrodes inserted to the left temporal muscle. In each condition, 120 pulses were delivered. The EEG was recorded from 60 scalp electrodes. A peak in the EEG signals was observed at 43 ms after the TMS pulse in the real-TMS condition but not in the control condition or in the control scalp EMG. Potential maps before and after ethanol ingestion were significantly different from each other (P = 0.01), but no differences were found in the control condition. Ethanol changed the TMS-evoked potentials over right frontal and left parietal areas, the underlying effect appearing to be largest in the right prefrontal area. Our findings suggest that ethanol may have changed the functional connectivity between prefrontal and motor cortices. This new noninvasive method provides direct evidence about the modulation of cortical connectivity after ethanol challenge. Copyright 2001 Academic Press.

Structural Brain Changes Following Left Temporal Low-Frequency rTMS in Patients with Subjective Tinnitus

PubMed Central

Langguth, Berthold; Poeppl, Timm B.; Rupprecht, Rainer; Hajak, Göran; Landgrebe, Michael; Schecklmann, Martin

2014-01-01

Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been used to treat patients with subjective tinnitus. While rTMS is known to induce morphological changes in healthy subjects, no study has investigated yet whether rTMS treatment induces grey matter (GM) changes in tinnitus patients as well, whether these changes are correlated with treatment success, and whether GM at baseline is a useful predictor for treatment outcome. Therefore, we examined magnetic resonance images of 77 tinnitus patients who were treated with rTMS of the left temporal cortex (10 days, 2000 stimuli/day, 1 Hz). At baseline and after the last treatment session high-resolution structural images of the brain were acquired and tinnitus severity was assessed. For a subgroup of 41 patients, additional brain scans were done after a follow-up period of 90 days. GM changes were analysed by means of voxel based morphometry. Transient GM decreases were detectable in several brain regions, especially in the insula and the inferior frontal cortex. These changes were not related to treatment outcome though. Baseline images correlated with change in tinnitus severity in the frontal cortex and the lingual gyrus, suggesting that GM at baseline might hold potential as a possible predictor for treatment outcome. PMID:24991438

Attention Modulates TMS-Locked Alpha Oscillations in the Visual Cortex.

PubMed

Herring, Jim D; Thut, Gregor; Jensen, Ole; Bergmann, Til O

2015-10-28

Cortical oscillations, such as 8-12 Hz alpha-band activity, are thought to subserve gating of information processing in the human brain. While most of the supporting evidence is correlational, causal evidence comes from attempts to externally drive ("entrain") these oscillations by transcranial magnetic stimulation (TMS). Indeed, the frequency profile of TMS-evoked potentials (TEPs) closely resembles that of oscillations spontaneously emerging in the same brain region. However, it is unclear whether TMS-locked and spontaneous oscillations are produced by the same neuronal mechanisms. If so, they should react in a similar manner to top-down modulation by endogenous attention. To test this prediction, we assessed the alpha-like EEG response to TMS of the visual cortex during periods of high and low visual attention while participants attended to either the visual or auditory modality in a cross-modal attention task. We observed a TMS-locked local oscillatory alpha response lasting several cycles after TMS (but not after sham stimulation). Importantly, TMS-locked alpha power was suppressed during deployment of visual relative to auditory attention, mirroring spontaneous alpha amplitudes. In addition, the early N40 TEP component, located at the stimulation site, was amplified by visual attention. The extent of attentional modulation for both TMS-locked alpha power and N40 amplitude did depend, with opposite sign, on the individual ability to modulate spontaneous alpha power at the stimulation site. We therefore argue that TMS-locked and spontaneous oscillations are of common neurophysiological origin, whereas the N40 TEP component may serve as an index of current cortical excitability at the time of stimulation. Copyright © 2015 Herring et al.

Role of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treatment of Addiction and Related Disorders: A Systematic Review.

PubMed

Makani, Ramkrishna; Pradhan, Basant; Shah, Umang; Parikh, Tapan

2017-11-29

Addiction and related disorders are devastating with their tremendous social, psychological, and physical consequences for which development of optimally effective treatments are long overdue. Repetitive transcranial magnetic stimulation (rTMS) is relatively safe and is becoming an emerging therapeutic tool for these conditions. This systematic review was conducted using PubMed, PsycINFO, PsychiatryOnline and Cochrane Library ranging from year 2001 to 2017. Our search retrieved 70 related articles of which, based on the Strength of Recommendation Taxonomy (SORT) guidelines, 33 indicated Level-1 study quality and class-B strength of recommendation for rTMS in nicotine addiction (effective in 218/289 subjects who received rTMS as found in 11 studies). Level-2/Class-B evidence was found for alcohol and cocaine addictions (Alcohol: effective in 126/193 subjects who received rTMS as found in 8 studies; Cocaine: effective in 86/128 subjects, as found in 5 studies). For food cravings, Level-3/Class-B evidence was noted (effective in 134/169, found in 7 studies). However, the evidence was limited to Level-3/Class-C for heroin (10/20 subjects received active rTMS, effective in 1 study), methamphetamine (33/48 subjects received active rTMS, effective in 2 studies), cannabis (18/18 subjects received active rTMS, effective in 1 study), and pathological gambling (31/31 subjects received active rTMS, effective in 2 studies). rTMS may serve as an emerging therapeutic option for addiction and related disorders. The major lacunae include important methodological limitations and dearth of knowledge about precise mechanism of action that need to be addressed in the future studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A novel approach for documenting naming errors induced by navigated transcranial magnetic stimulation.

PubMed

Lioumis, Pantelis; Zhdanov, Andrey; Mäkelä, Niko; Lehtinen, Henri; Wilenius, Juha; Neuvonen, Tuomas; Hannula, Henri; Deletis, Vedran; Picht, Thomas; Mäkelä, Jyrki P

2012-03-15

Transcranial magnetic stimulation (TMS) is widely used both in basic research and in clinical practice. TMS has been utilized in studies of functional organization of speech in healthy volunteers. Navigated TMS (nTMS) allows preoperative mapping of the motor cortex for surgical planning. Recording behavioral responses to nTMS in the speech-related cortical network in a manner that allows off-line review of performance might increase utility of nTMS both for scientific and clinical purposes, e.g., for a careful preoperative planning. Four subjects participated in the study. The subjects named pictures of objects presented every 2-3s on a computer screen. One-second trains of 5 pulses were applied by nTMS 300ms after the presentation of pictures. The nTMS and stimulus presentation screens were cloned. A commercial digital camera was utilized to record the subject's performance and the screen clones. Delays between presentation, audio and video signals were eliminated by carefully tested combination of displays and camera. An experienced neuropsychologist studied the videos and classified the errors evoked by nTMS during the object naming. Complete anomias, semantic, phonological and performance errors were observed during nTMS of left fronto-parieto-temporal cortical regions. Several errors were detected only in the video classification. nTMS combined with synchronized video recording provides an accurate monitoring tool of behavioral TMS experiments. This experimental setup can be particularly useful for high-quality cognitive paradigms and for clinical purposes. Copyright © 2011 Elsevier B.V. All rights reserved.

Mercury biomagnification in food webs of the northeastern Chukchi Sea, Alaskan Arctic

NASA Astrophysics Data System (ADS)

Fox, Austin L.; Trefry, John H.; Trocine, Robert P.; Dunton, Kenneth H.; Lasorsa, Brenda K.; Konar, Brenda; Ashjian, Carin J.; Cooper, Lee W.

2017-10-01

Predictive tools and a large new dataset for the northeastern Chukchi Sea (NECS) are used here to help identify regional differences and potential future shifts in the magnitude of Hg biomagnification in the Arctic. At the base of the food web in the NECS, concentrations of total mercury (THg) in phytoplankton (20-μm mesh) ranged from 4-42 ng g-1 dry weight, partly in response to variations in algal biomass and water temperature. A >3-fold increase in monomethylmercury (MMHg) was observed in zooplankton (4.3±0.7 ng g-1) relative to phytoplankton (<1.5 ng g-1), even though concentrations of THg in zooplankton (150-μm mesh) were not significantly different than in phytoplankton. Concentrations and % MMHg increased with trophic level (TL) by >150-fold and from <10 to >85%, respectively, from phytoplankton to muscle in the whelk Plicifusus kroeyeri (279 ng g-1, TL 4.5). For muscle tissue in 10 species plus whole phytoplankton and zooplankton, the trophic magnification slope (TMS) for MMHg (log10[MMHg]=m(δ15N)+b; where m=TMS) was 0.23±0.02 (SE). No significant differences in TMS were found for the NECS plus three other studies from the eastern Canadian Arctic (average TMS=0.24±0.02). Nevertheless, all data for MMHg in biota from the NECS plotted below the combined best fit line for all four studies. Results from an ANCOVA showed that statistically different (p=0.001) intercept values (b), not TMS, best explained the >2-fold lower concentrations of MMHg in biota from the NECS (b=-1.85) relative to the same species from the eastern Canadian Arctic (b=-1.29). Future changes that affect bioaccumulation of MMHg in the Arctic may impact the biomagnification equation by shifting the TMS, intercept or both. The intercept is more likely to respond to changes in productivity and concentrations of dissolved Hg whereas the TMS may respond to changing growth rates due to fluctuations in productivity and food availability. In either case, small changes in the intercept or TMS coincide with predictably large increases or decreases in MMHg concentrations in apex predators.

Dynamic behaviour of a two-microbubble system under ultrasonic wave excitation.

PubMed

Huang, Xiao; Wang, Qian-Xi; Zhang, A-Man; Su, Jian

2018-05-01

Acoustic bubbles have wide and important applications in ultrasonic cleaning, sonochemistry and medical ultrasonics. A two-microbubble system (TMS) under ultrasonic wave excitation is explored in the present study, by using the boundary element method (BEM) based on the potential flow theory. A parametric study of the behaviour of a TMS has been carried out in terms of the amplitude and direction of ultrasound as well as the sizes and separation distance of the two bubbles. Three regimes of the dynamic behaviour of the TMS have been identified in terms of the pressure amplitude of the ultrasonic wave. When subject to a strong wave with the pressure amplitude of 1 atm or larger, the two microbubbles become non-spherical during the first cycle of oscillation, with two counter liquid jets formed. When subject to a weak wave with the pressure amplitude of less than 0.5 atm, two microbubbles may be attracted, repelled, or translate along the wave direction with periodic stable separation distance, depending on their size ratio. However, for the TMS under moderate waves, bubbles undergo both non-spherical oscillation and translation as well as liquid jet rebounding. Copyright © 2018 Elsevier B.V. All rights reserved.

A review of tricaine methanesulfonate for anesthesia of fish

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

Carter, Kathleen M.; Woodley, Christa M.; Brown, Richard S.

2011-01-01

Tricaine methanesulfonate (TMS) is the only FDA approved anesthetic for use in a select number of fish species, including salmonids. It is used widely in hatcheries and research to immobilize fish for marking or transport and to suppress sensory systems during invasive procedures. Improper use can decrease fish viability and possibly distort physiological data. Since animals may be anesthetized by junior staff or students who may have little experience in fish anesthesia, training in the proper use of TMS may decrease variability in results and increase fish survival. This document acts as a primer on the use of TMS formore » anesthetizing juvenile salmonids, with an emphasis on its use in surgical applications. Within, we briefly discuss many aspects TMS. We describe the legal uses for TMS, and what is currently known about the proper storage and preparation of the anesthetic. We outline methods and precautions for administration and changes in fish behavior during progressively deeper anesthesia. We also discuss the physiological effects of TMS and its potential for decreasing fish health.« less

Electrical and magnetic repetitive transcranial stimulation of the primary motor cortex in healthy subjects.

PubMed

Gilio, Francesca; Iacovelli, Elisa; Frasca, Vittorio; Gabriele, Maria; Giacomelli, Elena; De Lena, Carlo; Cipriani, Anna Maria; Inghilleri, Maurizio

2009-05-08

Repetitive transcranial magnetic stimulation (rTMS) delivered in short trains at 5Hz frequency and suprathreshold intensity over the primary motor cortex (M1) in healthy subjects facilitates the motor-evoked potential (MEP) amplitude by increasing cortical excitability through mechanisms resembling short-term synaptic plasticity. In this study, to investigate whether rTES acts through similar mechanisms we compared the effects of rTMS and repetitive transcranial electrical stimulation (rTES) (10 stimuli-trains, 5Hz frequency, suprathreshold intensity) delivered over the M1 on the MEP amplitude. Four healthy subjects were studied in two separate sessions in a relaxed condition. rTMS and anodal rTES were delivered in trains to the left M1 over the motor area for evoking a MEP in the right first dorsal interosseous muscle. Changes in MEP size and latency during the course of the rTMS and rTES trains were compared. The possible effects of muscle activation on MEP amplitude were evaluated, and the possible effects of cutaneous trigeminal fibre activation on corticospinal excitability were excluded in a control experiment testing the MEP amplitude before and after supraorbital nerve repetitive electrical stimulation. Repeated measures analysis of variance (ANOVA) showed that rTES and rTMS trains elicited similar amplitude first MEPs and a similar magnitude MEP amplitude facilitation during the trains. rTES elicited a first MEP with a shorter latency than rTMS, without significant changes during the course of the train of stimuli. The MEP elicited by single-pulse TES delivered during muscle contraction had a smaller amplitude than the last MEP in the rTES trains. Repetitive supraorbital nerve stimulation left the conditioned MEP unchanged. Our results suggest that 5 Hz-rTES delivered in short trains increases cortical excitability and does so by acting on the excitatory interneurones probably through mechanisms similar to those underlying the rTMS-induced MEP facilitation.

Transcranial Magnetic Stimulation: An Automated Procedure to Obtain Coil-specific Models for Field Calculations.

PubMed

Madsen, Kristoffer H; Ewald, Lars; Siebner, Hartwig R; Thielscher, Axel

2015-01-01

Field calculations for transcranial magnetic stimulation (TMS) are increasingly implemented online in neuronavigation systems and in more realistic offline approaches based on finite-element methods. They are often based on simplified and/or non-validated models of the magnetic vector potential of the TMS coils. To develop an approach to reconstruct the magnetic vector potential based on automated measurements. We implemented a setup that simultaneously measures the three components of the magnetic field with high spatial resolution. This is complemented by a novel approach to determine the magnetic vector potential via volume integration of the measured field. The integration approach reproduces the vector potential with very good accuracy. The vector potential distribution of a standard figure-of-eight shaped coil determined with our setup corresponds well with that calculated using a model reconstructed from x-ray images. The setup can supply validated models for existing and newly appearing TMS coils. Copyright © 2015 Elsevier Inc. All rights reserved.

Safety of topical minoxidil solution: a one-year, prospective, observational study.

PubMed

Shapiro, Jerry

2003-01-01

Topical minoxidil solution (TMS) is widely used for androgenetic alopecia (AGA), and this is the first report of a large safety trial. The aim of the study was to evaluate the safety profile of TMS by comparing hospitalization and death rates among subjects using TMS with controls. Cardiovascular safety and pregnancy outcomes were evaluated, and usage patterns were described. All subjects were followed at baseline, 3, 6, 9, and 12 months. Usage patterns, pregnancy status, overnight hospital stays, and cardiovascular risk factors were evaluated. Subjects rated effectiveness of TMS in the treatment of AGA. Statistical analyses were conducted to determine if TMS was associated with an increased risk of death or hospitalization. TMS is a safe and effective treatment for AGA. There were no increases in cardiovascular events and no apparent increased risk for adverse pregnancy outcomes. This large, prospective study demonstrated the overall safety of TMS in the treatment of AGA.

A Comparison of Right Unilateral and Sequential Bilateral Repetitive Transcranial Magnetic Stimulation for Major Depression: A Naturalistic Clinical Australian Study.

PubMed

Galletly, Cherrie A; Carnell, Benjamin L; Clarke, Patrick; Gill, Shane

2017-03-01

A great deal of research has established the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. However, questions remain about the optimal method to deliver treatment. One area requiring consideration is the difference in efficacy between bilateral and unilateral treatment protocols. This study aimed to compare the effectiveness of sequential bilateral rTMS and right unilateral rTMS. A total of 135 patients participated in the study, receiving either bilateral rTMS (N = 57) or right unilateral rTMS (N = 78). Treatment response was assessed using the Hamilton depression rating scale. Sequential bilateral rTMS had a higher response rate than right unilateral (43.9% vs 30.8%), but this difference was not statistically significant. This was also the case for remission rates (33.3% vs 21.8%, respectively). Controlling for pretreatment severity of depression, the results did not indicate a significant difference between the protocols with regard to posttreatment Hamilton depression rating scale scores. The current study found no statistically significant differences in response and remission rates between sequential bilateral rTMS and right unilateral rTMS. Given the shorter treatment time and the greater safety and tolerability of right unilateral rTMS, this may be a better choice than bilateral treatment in clinical settings.

Dynamic aftereffects in supplementary motor network following inhibitory transcranial magnetic stimulation protocols.

PubMed

Ji, Gong-Jun; Yu, Fengqiong; Liao, Wei; Wang, Kai

2017-04-01

The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols [1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS)] on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or "protocol" main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Intracortical excitability in patients with relapsing-remitting and secondary progressive multiple sclerosis.

PubMed

Conte, A; Lenzi, D; Frasca, V; Gilio, F; Giacomelli, E; Gabriele, M; Bettolo, C Marini; Iacovelli, E; Pantano, P; Pozzilli, C; Inghilleri, M

2009-06-01

We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing-remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

Novel doping alternatives for single-layer transition metal dichalcogenides

NASA Astrophysics Data System (ADS)

Onofrio, Nicolas; Guzman, David; Strachan, Alejandro

2017-11-01

Successful doping of single-layer transition metal dichalcogenides (TMDs) remains a formidable barrier to their incorporation into a range of technologies. We use density functional theory to study doping of molybdenum and tungsten dichalcogenides with a large fraction of the periodic table. An automated analysis of the energetics, atomic and electronic structure of thousands of calculations results in insightful trends across the periodic table and points out promising dopants to be pursued experimentally. Beyond previously studied cases, our predictions suggest promising substitutional dopants that result in p-type transport and reveal interesting physics behind the substitution of the metal site. Doping with early transition metals (TMs) leads to tensile strain and a significant reduction in the bandgap. The bandgap increases and strain is reduced as the d-states are filled into the mid TMs; these trends reverse as we move into the late TMs. Additionally, the Fermi energy increases monotonously as the d-shell is filled from the early to mid TMs and we observe few to no gap states, indicating the possibility of both p- (early TMs) and n- (mid TMs) type doping. Quite surprisingly, the simulations indicate the possibility of interstitial doping of TMDs; the energetics reveal that a significant number of dopants, increasing in number from molybdenum disulfide to diselenide and to ditelluride, favor the interstitial sites over adsorbed ones. Furthermore, calculations of the activation energy associated with capturing the dopants into the interstitial site indicate that the process is kinetically possible. This suggests that interstitial impurities in TMDs are more common than thought to date and we propose a series of potential interstitial dopants for TMDs relevant for application in nanoelectronics based on a detailed analysis of the predicted electronic structures.

Numerical dosimetry of transcranial magnetic stimulation coils

NASA Astrophysics Data System (ADS)

Crowther, Lawrence; Hadimani, Ravi; Jiles, David

2014-03-01

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique capable of stimulating neurons by means of electromagnetic induction. TMS can be used to map brain function and shows promise for the diagnosis and treatment of neurological and psychiatric disorders. Calculation of fields induced in the brain are necessary to accurately identify stimulated neural tissue during TMS. This allows the development of novel TMS coil designs capable of stimulating deeper brain regions and increasing the localization of stimulation that can be achieved. We have performed numerical calculations of magnetic and electric field with high-resolution anatomically realistic human head models to find these stimulated brain regions for a variety of proposed TMS coil designs. The realistic head models contain heterogeneous tissue structures and electrical conductivities, yielding superior results to those obtained from the simplified homogeneous head models that are commonly employed. The attenuation of electric field as a function of depth in the brain and the localization of stimulating field have been methodically investigated. In addition to providing a quantitative comparison of different TMS coil designs the variation of induced field between subjects has been investigated. We also show the differences in induced fields between adult, adolescent and child head models to preemptively identify potential safety issues in the application of pediatric TMS.

Frontal Non-Invasive Neurostimulation Modulates Antisaccade Preparation in Non-Human Primates

PubMed Central

Valero-Cabre, Antoni; Wattiez, Nicolas; Monfort, Morgane; François, Chantal; Rivaud-Péchoux, Sophie; Gaymard, Bertrand; Pouget, Pierre

2012-01-01

A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes. PMID:22701691

A Role for the Left Angular Gyrus in Episodic Simulation and Memory.

PubMed

Thakral, Preston P; Madore, Kevin P; Schacter, Daniel L

2017-08-23

Functional magnetic resonance imaging (fMRI) studies indicate that episodic simulation (i.e., imagining specific future experiences) and episodic memory (i.e., remembering specific past experiences) are associated with enhanced activity in a common set of neural regions referred to as the core network. This network comprises the hippocampus, medial prefrontal cortex, and left angular gyrus, among other regions. Because fMRI data are correlational, it is unknown whether activity increases in core network regions are critical for episodic simulation and episodic memory. In the current study, we used MRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of the left angular gyrus would impair both episodic simulation and memory (16 participants, 10 females). Relative to TMS to a control site (vertex), disruption of the left angular gyrus significantly reduced the number of internal (i.e., episodic) details produced during the simulation and memory tasks, with a concomitant increase in external detail production (i.e., semantic, repetitive, or off-topic information), reflected by a significant detail by TMS site interaction. Difficulty in the simulation and memory tasks also increased after TMS to the left angular gyrus relative to the vertex. In contrast, performance in a nonepisodic control task did not differ statistically as a function of TMS site (i.e., number of free associates produced or difficulty in performing the free associate task). Together, these results are the first to demonstrate that the left angular gyrus is critical for both episodic simulation and episodic memory. SIGNIFICANCE STATEMENT Humans have the ability to imagine future episodes (i.e., episodic simulation) and remember episodes from the past (i.e., episodic memory). A wealth of neuroimaging studies have revealed that these abilities are associated with enhanced activity in a core network of neural regions, including the hippocampus, medial prefrontal cortex, and left angular gyrus. However, neuroimaging data are correlational and do not tell us whether core regions support critical processes for simulation and memory. In the current study, we used transcranial magnetic stimulation and demonstrated that temporary disruption of the left angular gyrus leads to impairments in simulation and memory. The present study provides the first causal evidence to indicate that this region is critical for these fundamental abilities. Copyright © 2017 the authors 0270-6474/17/378142-08$15.00/0.

A Role for the Left Angular Gyrus in Episodic Simulation and Memory

PubMed Central

2017-01-01

Functional magnetic resonance imaging (fMRI) studies indicate that episodic simulation (i.e., imagining specific future experiences) and episodic memory (i.e., remembering specific past experiences) are associated with enhanced activity in a common set of neural regions referred to as the core network. This network comprises the hippocampus, medial prefrontal cortex, and left angular gyrus, among other regions. Because fMRI data are correlational, it is unknown whether activity increases in core network regions are critical for episodic simulation and episodic memory. In the current study, we used MRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of the left angular gyrus would impair both episodic simulation and memory (16 participants, 10 females). Relative to TMS to a control site (vertex), disruption of the left angular gyrus significantly reduced the number of internal (i.e., episodic) details produced during the simulation and memory tasks, with a concomitant increase in external detail production (i.e., semantic, repetitive, or off-topic information), reflected by a significant detail by TMS site interaction. Difficulty in the simulation and memory tasks also increased after TMS to the left angular gyrus relative to the vertex. In contrast, performance in a nonepisodic control task did not differ statistically as a function of TMS site (i.e., number of free associates produced or difficulty in performing the free associate task). Together, these results are the first to demonstrate that the left angular gyrus is critical for both episodic simulation and episodic memory. SIGNIFICANCE STATEMENT Humans have the ability to imagine future episodes (i.e., episodic simulation) and remember episodes from the past (i.e., episodic memory). A wealth of neuroimaging studies have revealed that these abilities are associated with enhanced activity in a core network of neural regions, including the hippocampus, medial prefrontal cortex, and left angular gyrus. However, neuroimaging data are correlational and do not tell us whether core regions support critical processes for simulation and memory. In the current study, we used transcranial magnetic stimulation and demonstrated that temporary disruption of the left angular gyrus leads to impairments in simulation and memory. The present study provides the first causal evidence to indicate that this region is critical for these fundamental abilities. PMID:28733357

Actigraphy in Patients With Major Depressive Disorder Undergoing Repetitive Transcranial Magnetic Stimulation: An Open Label Pilot Study.

PubMed

Nishida, Masaki; Kikuchi, Senichiro; Nisijima, Koichi; Suda, Shiro

2017-03-01

The effects of repetitive transcranial magnetic stimulation (rTMS) on physical activity and sleep patterns in individuals with major depressive disorder (MDD) remain unclear. We examined the effects of rTMS treatment on the rest-activity cycle and sleep disturbances in MDD. In this open-label pilot study, 14 patients with medication-resistant MDD underwent 10 rTMS sessions over the bilateral dorsolateral prefrontal cortex. In addition to Hamilton Depression Rating Scale and Pittsburgh Sleep Quality Index scores, waist actigraphy was used to evaluate alterations in the rest-activity cycle over the course of rTMS treatments. Actigraphic data were evaluated at baseline and in the first (rTMS sessions 1-3), second (rTMS sessions 4-7), and third (rTMS sessions 8-10) sections. Although Hamilton Depression Rating Scale and Pittsburgh Sleep Quality Index scores were significantly improved by rTMS, sleep variables assessed by actigraphy did not show significant changes. However, post hoc tests indicated a significant increase in mean steps per day between the baseline and first section time points (P = 0.014; t13 = -2.316). Our data indicated that a daytime physical activity response to rTMS occurred in early sessions, whereas subjective symptom improvements were consistent across all sessions. Future double-blind placebo-controlled studies assessing the effects of rTMS on the rest-activity cycle and sleep disturbances in MDD are warranted.

Age-related changes in late I-waves influence motor cortex plasticity induction in older adults.

PubMed

Opie, George M; Cirillo, John; Semmler, John G

2018-04-18

The response to neuroplasticity interventions using transcranial magnetic stimulation (TMS) is reduced in older adults, which may be due, in part, to age-related alterations in interneuronal (I-wave) circuitry. The current study investigated age-related changes in interneuronal characteristics and whether they influence motor cortical plasticity in older adults. While I-wave recruitment was unaffected by age, there was a shift in the temporal characteristics of the late, but not early I-waves. Using I-wave periodicity repetitive TMS (iTMS), we showed that these differences in I-wave characteristics influence the induction of cortical plasticity in older adults. Previous research shows that neuroplasticity assessed using transcranial magnetic stimulation (TMS) is reduced in older adults. While this deficit is often assumed to represent altered synaptic modification processes, age-related changes in the interneuronal circuits activated by TMS may also contribute. Here we assessed age-related differences in the characteristics of the corticospinal indirect (I) waves and how they influence plasticity induction in primary motor cortex. Twenty young (23.7 ± 3.4 years) and 19 older adults (70.6 ± 6.0 years) participated in these studies. I-wave recruitment was assessed by changing the direction of the current used to activate the motor cortex, whereas short-interval intracortical facilitation (SICF) was recorded to assess facilitatory I-wave interactions. In a separate study, I-wave periodicity TMS (iTMS) was used to examine the effect of I-wave latency on motor cortex plasticity. Data from the motor evoked potential (MEP) onset latency produced using different coil orientations suggested that there were no age-related differences in preferential I-wave recruitment (P = 0.6). However, older adults demonstrated significant reductions in MEP facilitation at all 3 SICF peaks (all P-values < 0.05) and a delayed latency of the second and third SICF peaks (all P-values < 0.05). Using I-wave intervals that were optimal for young and older adults, these changes in the late I-waves were shown to influence the plasticity response in older adults after iTMS. These findings suggest that temporal characteristics are delayed for the late I-waves in older adults, and that optimising TMS interventions based on I-wave characteristics may improve the plasticity response in older adults. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effect of tensile mean stress on fatigue behavior of single-crystal and directionally solidified superalloys

NASA Technical Reports Server (NTRS)

Kalluri, Sreeramesh; Mcgaw, Michael A.

1990-01-01

Two nickel base superalloys, single crystal PWA 1480 and directionally solidified MAR-M 246 + Hf, were studied in view of the potential usage of the former and usage of the latter as blade materials for the turbomachinery of the space shuttle main engine. The baseline zero mean stress (ZMS) fatigue life (FL) behavior of these superalloys was established, and then the effect of tensile mean stress (TMS) on their FL behavior was characterized. At room temperature these superalloys have lower ductilities and higher strengths than most polycrystalline engineering alloys. The cycle stress-strain response was thus nominally elastic in most of the fatigue tests. Therefore, a stress range based FL prediction approach was used to characterize both the ZMS and TMS fatigue data. In the past, several researchers have developed methods to account for the detrimental effect of tensile mean stress on the FL for polycrystalline engineering alloys. However, the applicability of these methods to single crystal and directionally solidified superalloys has not been established. In this study, these methods were applied to characterize the TMS fatigue data of single crystal PWA 1480 and directionally solidified MAR-M 246 + Hf and were found to be unsatisfactory. Therefore, a method of accounting for the TMS effect on FL, that is based on a technique proposed by Heidmann and Manson was developed to characterize the TMS fatigue data of these superalloys. Details of this method and its relationship to the conventionally used mean stress methods in FL prediction are discussed.

Brain Stimulation in Alzheimer's Disease.

PubMed

Chang, Chun-Hung; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Brain stimulation techniques can modulate cognitive functions in many neuropsychiatric diseases. Pilot studies have shown promising effects of brain stimulations on Alzheimer's disease (AD). Brain stimulations can be categorized into non-invasive brain stimulation (NIBS) and invasive brain stimulation (IBS). IBS includes deep brain stimulation (DBS), and invasive vagus nerve stimulation (VNS), whereas NIBS includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), electroconvulsive treatment (ECT), magnetic seizure therapy (MST), cranial electrostimulation (CES), and non-invasive VNS. We reviewed the cutting-edge research on these brain stimulation techniques and discussed their therapeutic effects on AD. Both IBS and NIBS may have potential to be developed as novel treatments for AD; however, mixed findings may result from different study designs, patients selection, population, or samples sizes. Therefore, the efficacy of NIBS and IBS in AD remains uncertain, and needs to be further investigated. Moreover, more standardized study designs with larger sample sizes and longitudinal follow-up are warranted for establishing a structural guide for future studies and clinical application.

Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in Humans.

PubMed

Mineo, Ludovico; Concerto, Carmen; Patel, Dhaval; Mayorga, Tyrone; Paula, Michael; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

2017-01-01

Valeriana officinalis extract (VE) is a popular herbal medicine used for the treatment of anxiety and sleep disorders. Although the anxiolytic and sedative effects are mainly attributed to the modulation of GABA-ergic transmission, the mechanism of action has not been fully investigated in humans. Noninvasive brain stimulation protocols can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. In this study, we investigated the effects of a single dose of VE on cortical excitability as assessed with transcranial magnetic stimulation (TMS). Fifteen healthy volunteers participated in a double-blind, randomized, cross-over, placebo-controlled study. Subjects were required to take either 900 mg of VE (valerenic acid 0.8%) or placebo (an equal dose of vitamin E). Motor cortex excitability was studied by single and paired TMS before and at 1 h and 6 h after the oral administration. Cortical excitability was assessed using different TMS parameters: resting motor threshold, motor-evoked potential amplitude, cortical silent period, short-interval intracortical inhibition, and intracortical facilitation. Furthermore, we assessed sensorimotor integration by short-latency and long-latency afferent inhibition. We found a significant reduction in ICF, without any significant changes in other TMS measures of motor cortex excitability. The amount of ICF returned to baseline value 6 h after the intake of the VE. A single oral dose of VE modulates intracortical facilitatory circuits. Our results in healthy subjects could be predictive markers of treatment response in patients and further support the use of pharmaco-TMS to investigate the neuropsychiatric effects of herbal therapies in humans. © 2017 S. Karger AG, Basel.

Overt Naming fMRI Pre- and Post-TMS: Two Nonfluent Aphasia Patients, with and without Improved Naming Post-TMS

ERIC Educational Resources Information Center

Martin, Paula I.; Naeser, Margaret A.; Ho, Michael; Doron, Karl W.; Kurland, Jacquie; Kaplan, Jerome; Wang, Yunyan; Nicholas, Marjorie; Baker, Errol H.; Fregni, Felipe; Pascual-Leone, Alvaro

2009-01-01

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post-a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received 10, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a "good responder" with improved naming…

Transcranial magnetic stimulation-induced global propagation of transient phase resetting associated with directional information flow.

PubMed

Kawasaki, Masahiro; Uno, Yutaka; Mori, Jumpei; Kobata, Kenji; Kitajo, Keiichi

2014-01-01

Electroencephalogram (EEG) phase synchronization analyses can reveal large-scale communication between distant brain areas. However, it is not possible to identify the directional information flow between distant areas using conventional phase synchronization analyses. In the present study, we applied transcranial magnetic stimulation (TMS) to the occipital area in subjects who were resting with their eyes closed, and analyzed the spatial propagation of transient TMS-induced phase resetting by using the transfer entropy (TE), to quantify the causal and directional flow of information. The time-frequency EEG analysis indicated that the theta (5 Hz) phase locking factor (PLF) reached its highest value at the distant area (the motor area in this study), with a time lag that followed the peak of the transient PLF enhancements of the TMS-targeted area at the TMS onset. Phase-preservation index (PPI) analyses demonstrated significant phase resetting at the TMS-targeted area and distant area. Moreover, the TE from the TMS-targeted area to the distant area increased clearly during the delay that followed TMS onset. Interestingly, the time lags were almost coincident between the PLF and TE results (152 vs. 165 ms), which provides strong evidence that the emergence of the delayed PLF reflects the causal information flow. Such tendencies were observed only in the higher-intensity TMS condition, and not in the lower-intensity or sham TMS conditions. Thus, TMS may manipulate large-scale causal relationships between brain areas in an intensity-dependent manner. We demonstrated that single-pulse TMS modulated global phase dynamics and directional information flow among synchronized brain networks. Therefore, our results suggest that single-pulse TMS can manipulate both incoming and outgoing information in the TMS-targeted area associated with functional changes.

Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease.

PubMed

León Ruiz, M; Rodríguez Sarasa, M L; Sanjuán Rodríguez, L; Benito-León, J; García-Albea Ristol, E; Arce Arce, S

2016-05-06

Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic reality in post-stroke rehabilitation. It has a neuroprotective effect on the modulation of neuroplasticity, improving the brain's capacity to retrain neural circuits and promoting restoration and acquisition of new compensatory skills. We conducted a literature search on PubMed and also gathered the latest books, clinical practice guidelines, and recommendations published by the most prominent scientific societies concerning the therapeutic use of rTMS in the rehabilitation of stroke patients. The criteria of the International Federation of Clinical Neurophysiology (2014) were followed regarding the inclusion of all evidence and recommendations. Identifying stroke patients who are eligible for rTMS is essential to accelerate their recovery. rTMS has proven to be safe and effective for treating stroke complications. Functional brain activity can be optimised by applying excitatory or inhibitory electromagnetic pulses to the hemisphere ipsilateral or contralateral to the lesion, respectively, as well as at the level of the transcallosal pathway to regulate interhemispheric communication. Different studies of rTMS in these patients have resulted in improvements in motor disorders, aphasia, dysarthria, oropharyngeal dysphagia, depression, and perceptual-cognitive deficits. However, further well-designed randomized controlled clinical trials with larger sample size are needed to recommend with a higher level of evidence, proper implementation of rTMS use in stroke subjects on a widespread basis. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Efficacy, Safety and Tolerability of Augmentative rTMS in Treatment of Major Depressive Disorder (MDD): A Prospective Cohort Study in Croatia.

PubMed

Filipcic, Igor; Milovac, Zeljko; Sucic, Strahimir; Gajsak, Tomislav; Filipcic, Ivona Simunovic; Ivezic, Ena; Aljinovic, Vjekoslav; Orgulan, Ivana; Penic, Sandra Zecevic; Bajic, Zarko

2017-03-01

An increasing body of research suggest that repetitive Transcranial Magnetic Stimulation (rTMS) is effective and safe treatment option for patients with major depressive disorder (MDD). The Psychiatric Hospital "Sveti Ivan" has the first TMS laboratory with rTMS and deep TMS (dTMS) in Croatia. The objective of this study was to assess the efficacy, safety and tolerability of augmentative rTMS treatment vs standard treatment in Croatian patients with major depressive disorder (MDD). Total of 93 MDD patients were enrolled; 41 of them were treated by augmentative rTMS and 52 were treated by standard (psychopharmacotherapy and psychotherapy) therapy only. We delivered rTMS to the left dorsolateral prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration), 3000 pulses per session using a figure-eight coil, minimum of 20 sessions during four weeks. Our key outcome was the change in Hamilton Depression Scale (HAM-D17) result from baseline to 4 th week. Our secondary outcomes were changes in Hamilton Anxiety (HAM-A) and WHOQOL-BREF scales. After four weeks the changes of HAM-D17 and HAM-A results were significantly different between the group of patients treated by augmentative rTMS (48% and 53% decrease, respectively) and the group of patients treated by the standard therapy alone (24% and 30% decrease) (P=0.004, P=0.007). Absolute benefit increase defined as the difference between rates of remission (HAM-D17 ≤7) in rTMS and control group was 33% (P=0.001). Number of patients needed to treat with rTMS in order to achieve remission in one patient was NNT=3. In a group of patients treated with augmentative rTMS 21/41 (51%), and in control group 17/52 (33%) were responders (P=0.071). It seems that augmentative treatment with rTMS is more effective on depression and anxiety symptoms than standard therapy in MDD with equal safety and tolerability. Randomized, controlled studies are required to verify this finding.

An abundant tissue macrophage population in the adult murine heart with a distinct alternatively-activated macrophage profile.

PubMed

Pinto, Alexander R; Paolicelli, Rosa; Salimova, Ekaterina; Gospocic, Janko; Slonimsky, Esfir; Bilbao-Cortes, Daniel; Godwin, James W; Rosenthal, Nadia A

2012-01-01

Cardiac tissue macrophages (cTMs) are a previously uncharacterised cell type that we have identified and characterise here as an abundant GFP(+) population within the adult Cx(3)cr1(GFP/+) knock-in mouse heart. They comprise the predominant myeloid cell population in the myocardium, and are found throughout myocardial interstitial spaces interacting directly with capillary endothelial cells and cardiomyocytes. Flow cytometry-based immunophenotyping shows that cTMs exhibit canonical macrophage markers. Gene expression analysis shows that cTMs (CD45(+)CD11b(+)GFP(+)) are distinct from mononuclear CD45(+)CD11b(+)GFP(+) cells sorted from the spleen and brain of adult Cx(3)cr1(GFP/+) mice. Gene expression profiling reveals that cTMs closely resemble alternatively-activated anti-inflammatory M2 macrophages, expressing a number of M2 markers, including Mrc1, CD163, and Lyve-1. While cTMs perform normal tissue macrophage homeostatic functions, they also exhibit a distinct phenotype, involving secretion of salutary factors (including IGF-1) and immune modulation. In summary, the characterisation of cTMs at the cellular and molecular level defines a potentially important role for these cells in cardiac homeostasis.

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

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

Research with rTMS in the treatment of aphasia

PubMed Central

Naeser, Margaret A.; Martin, Paula I; Treglia, Ethan; Ho, Michael; Kaplan, Elina; Bashir, Shahid; Hamilton, Roy; Coslett, H. Branch; Pascual-Leone, Alvaro

2013-01-01

This review of our research with rTMS to treat aphasia contains four parts: Part 1 reviews functional brain imaging studies related to recovery of language in aphasia with emphasis on nonfluent aphasia. Part 2 presents the rationale for using rTMS to treat nonfluent aphasia patients (based on results from functional imaging studies). Part 2 also reviews our current rTMS treatment protocol used with nonfluent aphasia patients, and our functional imaging results from overt naming fMRI scans, obtained pre- and post- a series of rTMS treatments. Part 3 presents results from a pilot study where rTMS treatments were followed immediately by constraint-induced language therapy (CILT). Part 4 reviews our diffusion tensor imaging (DTI) study that examined white matter connections between the horizontal, midportion of the arcuate fasciculus (hAF) to different parts within Broca’s area (pars triangularis, PTr; pars opercularis, POp), and the ventral premotor cortex (vPMC) in the RH and in the LH. Part 4 also addresses some of the possible mechanisms involved with improved naming and speech, following rTMS with nonfluent aphasia patients. PMID:20714075

Cortical excitability and neurology: insights into the pathophysiology

PubMed Central

Badawy, Radwa A.B.; Loetscher, Tobias; Macdonell, Richard A.L.; Brodtmann, Amy

2012-01-01

Summary Transcranial magnetic stimulation (TMS) is a technique developed to non-invasively investigate the integrity of human motor corticospinal tracts. Over the last three decades, the use of stimulation paradigms including single-pulse TMS, paired-pulse TMS, repetitive TMS, and integration with EEG and functional imaging have been developed to facilitate measurement of cortical excitability. Through the use of these protocols, TMS has evolved into an excellent tool for measuring cortical excitability. TMS has high sensitivity in detecting subtle changes in cortical excitability, and therefore it is also a good measure of disturbances associated with brain disorders. In this review, we appraise the current literature on cortical excitability studies using TMS in neurological disorders. We begin with a brief overview of current TMS measures and then show how these have added to our understanding of the underlying mechanisms of brain disorders. PMID:23402674

TMS effects on subjective and objective measures of vision: stimulation intensity and pre- versus post-stimulus masking.

PubMed

de Graaf, Tom A; Cornelsen, Sonja; Jacobs, Christianne; Sack, Alexander T

2011-12-01

Transcranial magnetic stimulation (TMS) can be used to mask visual stimuli, disrupting visual task performance or preventing visual awareness. While TMS masking studies generally fix stimulation intensity, we hypothesized that varying the intensity of TMS pulses in a masking paradigm might inform several ongoing debates concerning TMS disruption of vision as measured subjectively versus objectively, and pre-stimulus (forward) versus post-stimulus (backward) TMS masking. We here show that both pre-stimulus TMS pulses and post-stimulus TMS pulses could strongly mask visual stimuli. We found no dissociations between TMS effects on the subjective and objective measures of vision for any masking window or intensity, ruling out the option that TMS intensity levels determine whether dissociations between subjective and objective vision are obtained. For the post-stimulus time window particularly, we suggest that these data provide new constraints for (e.g. recurrent) models of vision and visual awareness. Finally, our data are in line with the idea that pre-stimulus masking operates differently from conventional post-stimulus masking. Copyright © 2011 Elsevier Inc. All rights reserved.

Stochastic resonance effects reveal the neural mechanisms of transcranial magnetic stimulation

PubMed Central

Schwarzkopf, Dietrich Samuel; Silvanto, Juha; Rees, Geraint

2011-01-01

Transcranial magnetic stimulation (TMS) is a popular method for studying causal relationships between neural activity and behavior. However its mode of action remains controversial, and so far there is no framework to explain its wide range of facilitatory and inhibitory behavioral effects. While some theoretical accounts suggests that TMS suppresses neuronal processing, other competing accounts propose that the effects of TMS result from the addition of noise to neuronal processing. Here we exploited the stochastic resonance phenomenon to distinguish these theoretical accounts and determine how TMS affects neuronal processing. Specifically, we showed that online TMS can induce stochastic resonance in the human brain. At low intensity, TMS facilitated the detection of weak motion signals but with higher TMS intensities and stronger motion signals we found only impairment in detection. These findings suggest that TMS acts by adding noise to neuronal processing, at least in an online TMS protocol. Importantly, such stochastic resonance effects may also explain why TMS parameters that under normal circumstances impair behavior, can induce behavioral facilitations when the stimulated area is in an adapted or suppressed state. PMID:21368025

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

PubMed

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

2016-04-08

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

Low-Frequency rTMS Ameliorates Autistic-Like Behaviors in Rats Induced by Neonatal Isolation Through Regulating the Synaptic GABA Transmission

PubMed Central

Tan, Tao; Wang, Wei; Xu, Haitao; Huang, Zhilin; Wang, Yu Tian; Dong, Zhifang

2018-01-01

Patients with autism spectrum disorder (ASD) display abnormalities in neuronal development, synaptic function and neural circuits. The imbalance of excitatory and inhibitory (E/I) synaptic transmission has been proposed to cause the main behavioral characteristics of ASD. Repetitive transcranial magnetic stimulation (rTMS) can directly or indirectly induce excitability and synaptic plasticity changes in the brain noninvasively. However, whether rTMS can ameliorate autistic-like behaviors in animal model via regulating the balance of E/I synaptic transmission is unknown. By using our recent reported animal model with autistic-like behaviors induced by neonatal isolation (postnatal days 1–9), we found that low-frequency rTMS (LF-rTMS, 1 Hz) treatment for 2 weeks effectively alleviated the acquired autistic-like symptoms, as reflected by an increase in social interaction and decrease in self-grooming, anxiety- and depressive-like behaviors in young adult rats compared to those in untreated animals. Furthermore, the amelioration in autistic-like behavior was accompanied by a restoration of the balance between E/I activity, especially at the level of synaptic transmission and receptors in synaptosomes. These findings indicated that LF-rTMS may alleviate the symptoms of ASD-like behaviors caused by neonatal isolation through regulating the synaptic GABA transmission, suggesting that LF-rTMS may be a potential therapeutic technique to treat ASD. PMID:29541022

Efficacy of Add-On Deep Transcranial Magnetic Stimulation in Comorbid Alcohol Dependence and Dysthymic Disorder: Three Case Reports

PubMed Central

Rapinesi, Chiara; Serata, Daniele; Casale, Antonio Del; Bersani, Francesco S.; Solfanelli, Andrea; Scatena, Paola; Raccah, Ruggero N.; Brugnoli, Roberto; Digiacomantonio, Vittorio; Carbonetti, Paolo; Fensore, Claudio; Tatarelli, Roberto; Angeletti, Gloria; Ferracuti, Stefano; Girardi, Paolo

2013-01-01

Background: Craving for alcohol is associated with abnormal activation in the dorsolateral prefrontal cortex. Deep transcranial magnetic stimulation (dTMS) has shown promise in the treatment of depression. There are few treatment options for treatment-resistant dysthymic disorder comorbid with alcohol use disorder. Objective: To investigate the possible anticraving efficacy of bilateral dorsolateral prefrontal cortex high-frequency dTMS in 3 patients with comorbid long-term DSM-IV-TR dysthymic disorder and alcohol use disorder. Method: Three patients with alcohol use disorder with dysthymic disorder in their detoxification phase (abstaining for > 1 month) underwent twenty 20-minute sessions of 20 Hz dTMS over the dorsolateral prefrontal cortex over 28 days between 2011 and 2012. Alcohol craving was rated with the Obsessive Compulsive Drinking Scale and depressive symptoms with the Hamilton Depression Rating Scale. Results: All 3 patients responded unsatisfactorily to initial intravenous antidepressant and antianxiety combinations but responded after 10 dTMS sessions, improving on both anxiety-depressive symptoms and craving. This improvement enabled us to reduce antidepressant dosages after dTMS cycle completion. Discussion: High-frequency bilateral dorsolateral prefrontal cortex dTMS with left prevalence was found to produce significant anticraving effects in alcohol use disorder comorbid with dysthymic disorder. The potential of dTMS for reducing craving in patients with substance use disorder deserves to be further investigated. PMID:23724355

Efficacy of add-on deep transcranial magnetic stimulation in comorbid alcohol dependence and dysthymic disorder: three case reports.

PubMed

Rapinesi, Chiara; Kotzalidis, Georgios D; Serata, Daniele; Del Casale, Antonio; Bersani, Francesco S; Solfanelli, Andrea; Scatena, Paola; Raccah, Ruggero N; Brugnoli, Roberto; Digiacomantonio, Vittorio; Carbonetti, Paolo; Fensore, Claudio; Tatarelli, Roberto; Angeletti, Gloria; Ferracuti, Stefano; Girardi, Paolo

2013-01-01

Craving for alcohol is associated with abnormal activation in the dorsolateral prefrontal cortex. Deep transcranial magnetic stimulation (dTMS) has shown promise in the treatment of depression. There are few treatment options for treatment-resistant dysthymic disorder comorbid with alcohol use disorder. To investigate the possible anticraving efficacy of bilateral dorsolateral prefrontal cortex high-frequency dTMS in 3 patients with comorbid long-term DSM-IV-TR dysthymic disorder and alcohol use disorder. Three patients with alcohol use disorder with dysthymic disorder in their detoxification phase (abstaining for > 1 month) underwent twenty 20-minute sessions of 20 Hz dTMS over the dorsolateral prefrontal cortex over 28 days between 2011 and 2012. Alcohol craving was rated with the Obsessive Compulsive Drinking Scale and depressive symptoms with the Hamilton Depression Rating Scale. All 3 patients responded unsatisfactorily to initial intravenous antidepressant and antianxiety combinations but responded after 10 dTMS sessions, improving on both anxiety-depressive symptoms and craving. This improvement enabled us to reduce antidepressant dosages after dTMS cycle completion. High-frequency bilateral dorsolateral prefrontal cortex dTMS with left prevalence was found to produce significant anticraving effects in alcohol use disorder comorbid with dysthymic disorder. The potential of dTMS for reducing craving in patients with substance use disorder deserves to be further investigated.

Evaluation method for in situ electric field in standardized human brain for different transcranial magnetic stimulation coils

NASA Astrophysics Data System (ADS)

Iwahashi, Masahiro; Gomez-Tames, Jose; Laakso, Ilkka; Hirata, Akimasa

2017-03-01

This study proposes a method to evaluate the electric field induced in the brain by transcranial magnetic stimulation (TMS) to realize focal stimulation in the target area considering the inter-subject difference of the brain anatomy. The TMS is a non-invasive technique used for treatment/diagnosis, and it works by inducing an electric field in a specific area of the brain via a coil-induced magnetic field. Recent studies that report on the electric field distribution in the brain induced by TMS coils have been limited to simplified human brain models or a small number of detailed human brain models. Until now, no method has been developed that appropriately evaluates the coil performance for a group of subjects. In this study, we first compare the magnetic field and the magnetic vector potential distributions to determine if they can be used as predictors of the TMS focality derived from the electric field distribution. Next, the hotspots of the electric field on the brain surface of ten subjects using six coils are compared. Further, decisive physical factors affecting the focality of the induced electric field by different coils are discussed by registering the computed electric field in a standard brain space for the first time, so as to evaluate coil characteristics for a large population of subjects. The computational results suggest that the induced electric field in the target area cannot be generalized without considering the morphological variability of the human brain. Moreover, there was no remarkable difference between the various coils, although focality could be improved to a certain extent by modifying the coil design (e.g., coil radius). Finally, the focality estimated by the electric field was more correlated with the magnetic vector potential than the magnetic field in a homogeneous sphere.

Evaluation method for in situ electric field in standardized human brain for different transcranial magnetic stimulation coils.

PubMed

Iwahashi, Masahiro; Gomez-Tames, Jose; Laakso, Ilkka; Hirata, Akimasa

2017-03-21

This study proposes a method to evaluate the electric field induced in the brain by transcranial magnetic stimulation (TMS) to realize focal stimulation in the target area considering the inter-subject difference of the brain anatomy. The TMS is a non-invasive technique used for treatment/diagnosis, and it works by inducing an electric field in a specific area of the brain via a coil-induced magnetic field. Recent studies that report on the electric field distribution in the brain induced by TMS coils have been limited to simplified human brain models or a small number of detailed human brain models. Until now, no method has been developed that appropriately evaluates the coil performance for a group of subjects. In this study, we first compare the magnetic field and the magnetic vector potential distributions to determine if they can be used as predictors of the TMS focality derived from the electric field distribution. Next, the hotspots of the electric field on the brain surface of ten subjects using six coils are compared. Further, decisive physical factors affecting the focality of the induced electric field by different coils are discussed by registering the computed electric field in a standard brain space for the first time, so as to evaluate coil characteristics for a large population of subjects. The computational results suggest that the induced electric field in the target area cannot be generalized without considering the morphological variability of the human brain. Moreover, there was no remarkable difference between the various coils, although focality could be improved to a certain extent by modifying the coil design (e.g., coil radius). Finally, the focality estimated by the electric field was more correlated with the magnetic vector potential than the magnetic field in a homogeneous sphere.

Abnormal short-latency synaptic plasticity in the motor cortex of subjects with Becker muscular dystrophy: a rTMS study.

PubMed

Golaszewski, Stefan; Schwenker, Kerstin; Bergmann, Jürgen; Brigo, Francesco; Christova, Monica; Trinka, Eugen; Nardone, Raffaele

2016-01-01

We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate-dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The ethics of neuromodulation for anorexia nervosa: a focus on rTMS

PubMed Central

2014-01-01

Objective Recently there has been emerging clinical and research interest in the application of deep brain stimulation (DBS) and repetitive transcranial magnetic stimulation (rTMS) to the treatment of anorexia nervosa (AN). To our knowledge, few studies have discussed ethical aspects associated with the increased use of neuromodulation in AN, some of which are quite specific to AN, despite the rapid development and dissemination of these new technologies. Method We provide a brief overview of three published rTMS studies for AN and discuss ethical issues involved in the use of neuromodulation for AN. Results In contrast to neurosurgery or DBS, rTMS is a less invasive technique, with less associated risk, and thus has greater potential to become a more widespread augmentation or add-on therapy for AN. New therapeutic procedures are promising, yet they raise ethical questions regarding informed consent and patient selection. Illness-specific issues surrounding authenticity and autonomy are important to consider, ensuring an ethical approach to treatment for patients with AN. Discussion We argue that ethical investigations for neuromodulation techniques are timely and important, and discussions should go beyond the immediate goals of patient safety, consent, and risk and benefit, to consider broader ethical concepts such as authenticity and autonomy. PMID:24690315

Add-on deep Transcranial Magnetic Stimulation (dTMS) for the treatment of chronic migraine: A preliminary study.

PubMed

Rapinesi, Chiara; Del Casale, Antonio; Scatena, Paola; Kotzalidis, Georgios D; Di Pietro, Simone; Ferri, Vittoria Rachele; Bersani, Francesco Saverio; Brugnoli, Roberto; Raccah, Ruggero Nessim; Zangen, Abraham; Ferracuti, Stefano; Orzi, Francesco; Girardi, Paolo; Sette, Giuliano

2016-06-03

Deep Transcranial Magnetic Stimulation (dTMS) can be an alternative treatment to relieve pain in chronic migraine (CM). The aim of this study was to evaluate the effect of high-frequency dTMS in add-on to standard treatment for CM in patients not responding to effective abortive or preventive drug treatment. We randomized 14 patients with International Classification of Headache Disorders, 3rd Edition (ICHD-3) treatment-resistant CM to add-on dTMS (n=7) or standard abortive or preventive antimigraine treatment (n=7). Three sessions of alternate day 10Hz dTMS consisting of 600 pulses in 10 trains were delivered to the dorsolateral prefrontal cortex (DLPFC), bilaterally, but with left hemisphere prevalence, for 12 sessions spread over one month. The add-on dTMS treatment was well tolerated. Patients treated with dTMS showed significant reduction of pain intensity, frequency of attacks, analgesic overuse, and depressive symptoms during treatment and one month later, compared to the month preceding treatment and at the same time-points compared to the control group. As compared to standard pharmacological treatment alone, add-on high-frequency dTMS of the bilateral DLPFC reduced the frequency and intensity of migraine attack, drug overuse, and depressive symptoms. This study supports the add-on dTMS treatment in treatment-resistant CM. Copyright © 2016. Published by Elsevier Ireland Ltd.

Probing phase- and frequency-dependent characteristics of cortical interneurons using combined transcranial alternating current stimulation and transcranial magnetic stimulation.

PubMed

Hussain, Sara J; Thirugnanasambandam, Nivethida

2017-06-01

Paired-pulse transcranial magnetic stimulation (TMS) and peripheral stimulation combined with TMS can be used to study cortical interneuronal circuitry. By combining these procedures with concurrent transcranial alternating current stimulation (tACS), Guerra and colleagues recently showed that different cortical interneuronal populations are differentially modulated by the phase and frequency of tACS-imposed oscillations (Guerra A, Pogosyan A, Nowak M, Tan H, Ferreri F, Di Lazzaro V, Brown P. Cerebral Cortex 26: 3977-2990, 2016). This work suggests that different cortical interneuronal populations can be characterized by their phase and frequency dependency. Here we discuss how combining TMS and tACS can reveal the frequency at which cortical interneuronal populations oscillate, the neuronal origins of behaviorally relevant cortical oscillations, and how entraining cortical oscillations could potentially treat brain disorders. Copyright © 2017 the American Physiological Society.

A novel coil array for combined TMS/fMRI experiments at 3 T.

PubMed

Navarro de Lara, Lucia I; Windischberger, Christian; Kuehne, Andre; Woletz, Michael; Sieg, Jürgen; Bestmann, Sven; Weiskopf, Nikolaus; Strasser, Bernhard; Moser, Ewald; Laistler, Elmar

2015-11-01

To overcome current limitations in combined transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) studies by employing a dedicated coil array design for 3 Tesla. The state-of-the-art setup for concurrent TMS/fMRI is to use a large birdcage head coil, with the TMS between the subject's head and the MR coil. This setup has drawbacks in sensitivity, positioning, and available imaging techniques. In this study, an ultraslim 7-channel receive-only coil array for 3 T, which can be placed between the subject's head and the TMS, is presented. Interactions between the devices are investigated and the performance of the new setup is evaluated in comparison to the state-of-the-art setup. MR sensitivity obtained at the depth of the TMS stimulation is increased by a factor of five. Parallel imaging with an acceleration factor of two is feasible with low g-factors. Possible interactions between TMS and the novel hardware were investigated and were found negligible. The novel coil array is safe, strongly improves signal-to-noise ratio in concurrent TMS/fMRI experiments, enables parallel imaging, and allows for flexible positioning of the TMS on the head while ensuring efficient TMS stimulation due to its ultraslim design. © 2014 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation

PubMed Central

Li, Bingshuo; Virtanen, Juha P; Oeltermann, Axel; Schwarz, Cornelius; Giese, Martin A; Ziemann, Ulf

2017-01-01

Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8–1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6–300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain. PMID:29165241

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: An Economic Analysis

PubMed Central

Tu, Hong Anh; Palimaka, Stefan; Sehatzadeh, Shayan; Blackhouse, Gord; Yap, Belinda; Tsoi, Bernice; Bowen, Jim; O'Reilly, Daria; Holubowich, Corinne; Kaulback, Kellee; Campbell, Kaitryn

2016-01-01

Background Major depressive disorder (MDD, 10% over a person's lifetime) is common and costly to the health system. Unfortunately, many MDD cases are resistant to treatment with antidepressant drugs and require other treatment to reduce or eliminate depression. Electroconvulsive therapy (ECT) has long been used to treat persons with treatment-resistant depression (TRD). Despite its effectiveness, ECT has side effects that make patients intolerant to the treatment, or they refuse to use it. Repetitive transcranial magnetic stimulation (rTMS), which has fewer side effects than ECT and might be an alternative for TRD patients who are ineligible for or unwilling to undergo ECT, has been developed to treat TRD. Objectives This analysis evaluates the cost-effectiveness of rTMS for patients with TRD compared with ECT or sham rTMS and estimates the potential budgetary impact of various levels of implementation of rTMS in Ontario. Review Methods A cost-utility analysis compared the costs and health outcomes of two treatments for persons with TRD in Ontario: rTMS alone compared with ECT alone and rTMS alone compared with sham rTMS. We calculated the six-month incremental costs and quality-adjusted life-years (QALYs) for these treatments. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model's results. A 1-year budget impact analysis estimated the costs of providing funding for rTMS. The base-case analysis examined the additional costs for funding six centres, where rTMS infrastructure is in place. Sensitivity and scenario analyses explored the impact of increasing diffusion of rTMS to centres with existing ECT infrastructure. All analyses were conducted from the Ontario health care payer perspective. Results ECT was cost effective compared to rTMS when the willingness to pay is greater than $37,640.66 per QALY. In the base-case analysis, which had a six-month time horizon, the cost and effectiveness for rTMS was $5,272 and 0.31 quality-adjusted life-years (QALYs). The cost and effectiveness for ECT were $5,960 and 0.32 QALYs. This translates in an incremental cost-effectiveness ratio of $37,640.66 per QALY gained for ECT compared to rTMS. When rTMS is compared with sham rTMS, an additional $2,154.33 would be spent to gain 0.02 QALY. This translates to an ICER of $98,242.37 per QALY gained. Probabilistic sensitivity analysis showed that the probability of rTMS being cost-effective compared to sham rTMS was 2% and 45% at the thresholds of $50,000 and $100,000 per QALY gained, respectively. Conclusions Repetitive transcranial magnetic stimulation may be cost-effective compared to sham treatment in patients with treatment-resistant depression, depending on the willingness-to-pay threshold. PMID:27110317

The use of transcranial magnetic stimulation to evaluate cortical excitability of lower limb musculature: Challenges and opportunities.

PubMed

Kesar, Trisha M; Stinear, James W; Wolf, Steven L

2018-05-05

Neuroplasticity is a fundamental yet relatively unexplored process that can impact rehabilitation of lower extremity (LE) movements. Transcranial magnetic stimulation (TMS) has gained widespread application as a non-invasive brain stimulation technique for evaluating neuroplasticity of the corticospinal pathway. However, a majority of TMS studies have been performed on hand muscles, with a paucity of TMS investigations focused on LE muscles. This perspective review paper proposes that there are unique methodological challenges associated with using TMS to evaluate corticospinal excitability of lower limb muscles. The challenges include: (1) the deeper location of the LE motor homunculus; (2) difficulty with targeting individual LE muscles during TMS; and (3) differences in corticospinal circuity controlling upper and lower limb muscles. We encourage future investigations that modify traditional methodological approaches to help address these challenges. Systematic TMS investigations are needed to determine the extent of overlap in corticomotor maps for different LE muscles. A simple, yet informative methodological solution involves simultaneous recordings from multiple LE muscles, which will provide the added benefit of observing how other relevant muscles co-vary in their responses during targeted TMS assessment directed toward a specific muscle. Furthermore, conventionally used TMS methods (e.g., determination of hot spot location and motor threshold) may need to be modified for TMS studies involving LE muscles. Additional investigations are necessary to determine the influence of testing posture as well as activation state of adjacent and distant LE muscles on TMS-elicited responses. An understanding of these challenges and solutions specific to LE TMS will improve the ability of neurorehabilitation clinicians to interpret TMS literature, and forge novel future directions for neuroscience research focused on elucidating neuroplasticity processes underlying locomotion and gait training.

Structural Organization of the Corpus Callosum Predicts Attentional Shifts after Continuous Theta Burst Stimulation.

PubMed

Chechlacz, Magdalena; Humphreys, Glyn W; Sotiropoulos, Stamatios N; Kennard, Christopher; Cazzoli, Dario

2015-11-18

Repetitive transcranial magnetic stimulation (rTMS) applied over the right posterior parietal cortex (PPC) in healthy participants has been shown to trigger a significant rightward shift in the spatial allocation of visual attention, temporarily mimicking spatial deficits observed in neglect. In contrast, rTMS applied over the left PPC triggers a weaker or null attentional shift. However, large interindividual differences in responses to rTMS have been reported. Studies measuring changes in brain activation suggest that the effects of rTMS may depend on both interhemispheric and intrahemispheric interactions between cortical loci controlling visual attention. Here, we investigated whether variability in the structural organization of human white matter pathways subserving visual attention, as assessed by diffusion magnetic resonance imaging and tractography, could explain interindividual differences in the effects of rTMS. Most participants showed a rightward shift in the allocation of spatial attention after rTMS over the right intraparietal sulcus (IPS), but the size of this effect varied largely across participants. Conversely, rTMS over the left IPS resulted in strikingly opposed individual responses, with some participants responding with rightward and some with leftward attentional shifts. We demonstrate that microstructural and macrostructural variability within the corpus callosum, consistent with differential effects on cross-hemispheric interactions, predicts both the extent and the direction of the response to rTMS. Together, our findings suggest that the corpus callosum may have a dual inhibitory and excitatory function in maintaining the interhemispheric dynamics that underlie the allocation of spatial attention. The posterior parietal cortex (PPC) controls allocation of attention across left versus right visual fields. Damage to this area results in neglect, characterized by a lack of spatial awareness of the side of space contralateral to the brain injury. Transcranial magnetic stimulation over the PPC is used to study cognitive mechanisms of spatial attention and to examine the potential of this technique to treat neglect. However, large individual differences in behavioral responses to stimulation have been reported. We demonstrate that the variability in the structural organization of the corpus callosum accounts for these differences. Our findings suggest novel dual mechanism of the corpus callosum function in spatial attention and have broader implications for the use of stimulation in neglect rehabilitation. Copyright © 2015 the authors 0270-6474/15/3515353-16$15.00/0.

Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review.

PubMed

Pereira, Luisa Santos; Müller, Vanessa Teixeira; da Mota Gomes, Marleide; Rotenberg, Alexander; Fregni, Felipe

2016-04-01

Approximately one-third of patients with epilepsy remain with pharmacologically intractable seizures. An emerging therapeutic modality for seizure suppression is repetitive transcranial magnetic stimulation (rTMS). Despite being considered a safe technique, rTMS carries the risk of inducing seizures, among other milder adverse events, and thus, its safety in the population with epilepsy should be continuously assessed. We performed an updated systematic review on the safety and tolerability of rTMS in patients with epilepsy, similar to a previous report published in 2007 (Bae EH, Schrader LM, Machii K, Alonso-Alonso M, Riviello JJ, Pascual-Leone A, Rotenberg A. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Epilepsy Behav. 2007; 10 (4): 521-8), and estimated the risk of seizures and other adverse events during or shortly after rTMS application. We searched the literature for reports of rTMS being applied on patients with epilepsy, with no time or language restrictions, and obtained studies published from January 1990 to August 2015. A total of 46 publications were identified, of which 16 were new studies published after the previous safety review of 2007. We noted the total number of subjects with epilepsy undergoing rTMS, medication usage, incidence of adverse events, and rTMS protocol parameters: frequency, intensity, total number of stimuli, train duration, intertrain intervals, coil type, and stimulation site. Our main data analysis included separate calculations for crude per subject risk of seizure and other adverse events, as well as risk per 1000 stimuli. We also performed an exploratory, secondary analysis on the risk of seizure and other adverse events according to the type of coil used (figure-of-8 or circular), stimulation frequency (≤ 1 Hz or > 1 Hz), pulse intensity in terms of motor threshold (<100% or ≥ 100%), and number of stimuli per session (< 500 or ≥ 500). Presence or absence of adverse events was reported in 40 studies (n = 426 subjects). A total of 78 (18.3%) subjects reported adverse events, of which 85% were mild. Headache or dizziness was the most common one, occurring in 8.9%. We found a crude per subject seizure risk of 2.9% (95% CI: 1.3-4.5), given that 12 subjects reported seizures out of 410 subjects included in the analysis after data of patients with epilepsia partialis continua or status epilepticus were excluded from the estimate. Only one of the reported seizures was considered atypical in terms of the clinical characteristics of the patients' baseline seizures. The atypical seizure happened during high-frequency rTMS with maximum stimulator output for speech arrest, clinically arising from the region of stimulation. Although we estimated a larger crude per subject seizure risk compared with the previous safety review, the corresponding confidence intervals contained both risks. Furthermore, the exclusive case of atypical seizure was the same as reported in the previous report. We conclude that the risk of seizure induction in patients with epilepsy undergoing rTMS is small and that the risk of other adverse events is similar to that of rTMS applied to other conditions and to healthy subjects. Our results should be interpreted with caution, given the need for adjusted analysis controlling for potential confounders, such as baseline seizure frequency. The similarity between the safety profiles of rTMS applied to the population with epilepsy and to individuals without epilepsy supports further investigation of rTMS as a therapy for seizure suppression. Copyright © 2016. Published by Elsevier Inc.

Motor Cortex Reorganization in Patients with Glioma Assessed by Repeated Navigated Transcranial Magnetic Stimulation-A Longitudinal Study.

PubMed

Barz, Anne; Noack, Anika; Baumgarten, Peter; Seifert, Volker; Forster, Marie-Therese

2018-04-01

Evidence for cerebral reorganization after resection of low-grade glioma has mainly been obtained by serial intraoperative cerebral mapping. Noninvasively collected data on cortical plasticity in tumor patients over a surgery-free period are still scarce. The present study therefore aimed at evaluating motor cortex reorganization by navigated transcranial magnetic stimulation (nTMS) in patients after perirolandic glioma surgery. nTMS was performed preoperatively and postoperatively in 20 patients, separated by 26.1 ± 24.8 months. Further nTMS mapping was conducted in 14 patients, resulting in a total follow-up period of 46.3 ± 25.4 months. Centers of gravity (CoGs) were calculated for every muscle representation area, and Euclidian distances between CoGs over time were defined. Results were compared with data from 12 healthy individuals, who underwent motor cortex mapping by nTMS in 2 sessions. Preoperatively and postoperatively pooled CoGs from the area of the dominant abductor pollicis brevis muscle and of the nondominant leg area differed significantly compared with healthy individuals (P < 0.05). Most remarkably, during the ensuing follow-up period, a reorganization of all representation areas was observed in 3 patients, and a significant shift of hand representation areas was identified in further 3 patients. Complete functional recovery of postoperative motor deficits was exclusively associated with cortical reorganization. Despite the low potential of remodeling within the somatosensory region, long-term reorganization of cortical motor function can be observed. nTMS is best suited for a noninvasive evaluation of this reorganization. Copyright © 2018 Elsevier Inc. All rights reserved.

A versatile 3D tissue matrix scaffold system for tumor modeling and drug screening

PubMed Central

Rijal, Girdhari; Li, Weimin

2017-01-01

Most of the anticancer drug candidates entering preclinical trials fail to be approved for clinical applications. The following are among the main causes of these failures: studying molecular mechanisms of cancer development, identifying therapeutic targets, and testing drug candidates using inappropriate tissue culture models, which do not recapitulate the native microenvironment where the cancer cells originate. It has become clear that three-dimensional (3D) cell cultures are more biologically and clinically relevant than 2D models. The spatial and mechanical conditions of 3D cultures enable the cancer cells to display heterogeneous growth, assume diverse phenotypes, express distinct gene and protein products, and attain metastatic potential and resistance to drugs that are reminiscent of tumors in humans. However, the current 3D culture systems using synthetic polymers or selected components of the extracellular matrix (ECM) are defective (particularly the biophysical and biochemical properties of the native ECM) and remain distant to optimally support the signaling cue–oriented cell survival and growth. We introduce a reconstitutable tissue matrix scaffold (TMS) system fabricated using native tissue ECM, with tissue-like architecture and resilience. The structural and compositional properties of TMS favor robust cell survival, proliferation, migration, and invasion in culture and vascularized tumor formation in animals. The combination of porous and hydrogel TMS allows compartmental culture of cancerous and stromal cells, which are distinguishable by biomarkers. The response of the cancer cells grown on TMS to drugs well reflects animal and clinical observations. TMS enables more biologically relevant studies and is suitable for preclinical drug screening. PMID:28924608

Randomised sham-controlled study of high-frequency bilateral deep transcranial magnetic stimulation (dTMS) to treat adult attention hyperactive disorder (ADHD): Negative results.

PubMed

Paz, Yaniv; Friedwald, Keren; Levkovitz, Yeheal; Zangen, Abraham; Alyagon, Uri; Nitzan, Uri; Segev, Aviv; Maoz, Hagai; Koubi, May; Bloch, Yuval

2017-01-31

Recent studies support the possible effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a treatment for attention deficit hyperactivity disorder (ADHD). The objective of this study was to evaluate the safety and possible efficacy of bilateral prefrontal deep rTMS for the treatment of adult ADHD. Twenty-six adult ADHD patients were randomised blindly to sham or actual deep TMS (dTMS). Twenty daily sessions were conducted using the bilateral H5 dTMS coil (Brainsway, IL) in order to stimulate the prefrontal cortex at 120% of the motor threshold at high frequency. For assessment, Conners' Adult ADHD Rating Scale questionnaire and a computerised continuous performance test, Test of Variables of Attention, were used. No differences in clinical outcomes were detected between the actual dTMS and sham groups. The presented evidence does not support the utility of bilateral prefrontal stimulation to treat adult ADHD. Due to the small sample size, caution must be exercised in interpreting our preliminary findings.

Motoneuron excitability of the quadriceps decreases during a fatiguing submaximal isometric contraction.

PubMed

Finn, Harrison T; Rouffet, David M; Kennedy, David S; Green, Simon; Taylor, Janet L

2018-04-01

During fatiguing voluntary contractions, the excitability of motoneurons innervating arm muscles decreases. However, the behavior of motoneurons innervating quadriceps muscles is unclear. Findings may be inconsistent because descending cortical input influences motoneuron excitability and confounds measures during exercise. To overcome this limitation, we examined effects of fatigue on quadriceps motoneuron excitability tested during brief pauses in descending cortical drive after transcranial magnetic stimulation (TMS). Participants ( n = 14) performed brief (~5-s) isometric knee extension contractions before and after a 10-min sustained contraction at ~25% maximal electromyogram (EMG) of vastus medialis (VM) on one ( n = 5) or two ( n = 9) days. Electrical stimulation over thoracic spine elicited thoracic motor evoked potentials (TMEP) in quadriceps muscles during ongoing voluntary drive and 100 ms into the silent period following TMS (TMS-TMEP). Femoral nerve stimulation elicited maximal M-waves (M max ). On the 2 days, either large (~50% M max ) or small (~15% M max ) TMS-TMEPs were elicited. During the 10-min contraction, VM EMG was maintained ( P = 0.39), whereas force decreased by 52% (SD 13%) ( P < 0.001). TMEP area remained unchanged ( P = 0.9), whereas large TMS-TMEPs decreased by 49% (SD 28%) ( P = 0.001) and small TMS-TMEPs by 71% (SD 22%) ( P < 0.001). This decline was greater for small TMS-TMEPs ( P = 0.019; n = 9). Therefore, without the influence of descending drive, quadriceps TMS-TMEPs decreased during fatigue. The greater reduction for smaller responses, which tested motoneurons that were most active during the contraction, suggests a mechanism related to repetitive activity contributes to reduced quadriceps motoneuron excitability during fatigue. By contrast, the unchanged TMEP suggests that ongoing drive compensates for altered motoneuron excitability. NEW & NOTEWORTHY We provide evidence that the excitability of quadriceps motoneurons decreases with fatigue. Our results suggest that altered intrinsic properties brought about by repetitive activation of the motoneurons underlie their decreased excitability. Furthermore, we note that testing during voluntary contraction may not reflect the underlying depression of motoneuron excitability because of compensatory changes in ongoing voluntary drive. Thus, this study provides evidence that processes intrinsic to the motoneuron contribute to muscle fatigue of the knee extensors.

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

PubMed Central

Shafi, Mouhsin M.; Whitfield-Gabrieli, Susan; Chu, Catherine J.; Pascual-Leone, Alvaro; Chang, Bernard S.

2017-01-01

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases. PMID:27911366

Chemical composition and nutritive value of four varieties of cassava leaves grown in South-Western Nigeria.

PubMed

Oni, A O; Onwuka, C F I; Arigbede, O M; Anele, U Y; Oduguwa, O O; Onifade, O S; Tan, Z L

2011-10-01

The nutritive value of leaves of four varieties of cassava - MS 6, TMS 30555, Idileruwa and TMS 30572 was evaluated based on their chemical composition and in vitro fermentation. Crude protein (CP) contents of cassava leaves ranged from 177 to 240 g/kg dry matter (DM), with TMS 30555 showing the highest CP contents. Neutral detergent fibre (NDFom) and acid detergent fibre (ADFom) contents of cassava leaves ranged from 596 to 662 and 418 to 546 g/kg DM respectively. Condensed tannin (CT) and hydrocyanic acid contents ranged from 1.0 to 3.8 g/kg and 58.5 to 86.7 mg/kg DM respectively. The range of volatile fatty acids (VFA) in the supernatant after in vitro incubation of the cassava varieties was: acetate (14.7-31.5 mmol/l); propionate (4.5-6.3 mmol/l); butyrate (3.1-3.9 mmol/l); valerate (0.4-0.6 mmol/l); iso-butyrate (0.6-1.3 mmol/l); iso-valerate (1.1-1.9 mmol/l). The acetate:propionate ratio resulting from fermentation of TMS 30555 was higher(p < 0.05) than that of the other leaves. The highest in vitro gas production of 50.5 ml/200 mg DM was recorded for MS6 being higher (p < 0.05) than for TMS 30572, but similar to TMS 30555 and Idileruwa. The DM, CP, ADF and HCN contents of cassava leaves were positively correlated with gas production, while CT content was negatively correlated with gas production. The study showed that leaves of the varieties MS 6 and TMS 30555 are superior to the others in terms of CP and gas production indicating a higher digestibility and energy content and thus nutritive potential. They may therefore serve as supplements for ruminants fed on poor roughages. © 2010 Blackwell Verlag GmbH.

Fine Tuned Modulation of the Motor System by Adjectives Expressing Positive and Negative Properties

ERIC Educational Resources Information Center

Gough, P. M.; Campione, G. C.; Buccino, G.

2013-01-01

Using transcranial magnetic stimulation (TMS), motor evoked potentials (MEPs) were recorded from two antagonistic muscles, the first dorsal interosseus (FDI) of the hand and the extensor communis digitorum (EC) of the forearm. FDI is involved in grasping actions and EC in releasing. TMS pulses were delivered while participants were reading…

Language Mapping with Navigated Repetitive TMS: Proof of Technique and Validation

PubMed Central

Tarapore, Phiroz E.; Findlay, Anne M.; Honma, Susanne M.; Mizuiri, Danielle; Houde, John F.; Berger, Mitchel S.; Nagarajan, Srikantan S.

2013-01-01

Objective Lesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation (nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS. Methods Subjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared. Results nTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects. Conclusion Maps of language function generated with nTMS correlate well with those generated by DCS. Negative nTMS mapping also correlates with negative DCS mapping. In our study, MEGI lacks the same level of correlation with intraoperative mapping; nevertheless it provides useful adjunct information in some cases. nTMS may offer a lesion-based method for noninvasively interrogating language pathways and be valuable in managing patients with peri-eloquent lesions. PMID:23702420

Targeted therapies using electrical and magnetic neural stimulation for the treatment of chronic pain in spinal cord injury.

PubMed

Moreno-Duarte, Ingrid; Morse, Leslie R; Alam, Mahtab; Bikson, Marom; Zafonte, Ross; Fregni, Felipe

2014-01-15

Chronic neuropathic pain is one of the most common and disabling symptoms in individuals with spinal cord injury (SCI). Over two-thirds of subjects with SCI suffer from chronic pain influencing quality of life, rehabilitation, and recovery. Given the refractoriness of chronic pain to most pharmacological treatments, the majority of individuals with SCI report worsening of this condition over time. Moreover, only 4-6% of patients in this cohort report improvement. Novel treatments targeting mechanisms associated with pain-maladaptive plasticity, such as electromagnetic neural stimulation, may be desirable to improve outcomes. To date, few, small clinical trials have assessed the effects of invasive and noninvasive nervous system stimulation on pain after SCI. We aimed to review initial efficacy, safety and potential predictors of response by assessing the effects of neural stimulation techniques to treat SCI pain. A literature search was performed using the PubMed database including studies using the following targeted stimulation strategies: transcranial Direct Current Stimulation (tDCS), High Definition tDCS (HD-tDCS), repetitive Transcranial Magnetical Stimulation (rTMS), Cranial Electrotherapy Stimulation (CES), Transcutaneous Electrical Nerve Stimulation (TENS), Spinal Cord Stimulation (SCS) and Motor Cortex Stimulation (MCS), published prior to June of 2012. We included studies from 1998 to 2012. Eight clinical trials and one naturalistic observational study (nine studies in total) met the inclusion criteria. Among the clinical trials, three studies assessed the effects of tDCS, two of CES, two of rTMS and one of TENS. The naturalistic study investigated the analgesic effects of SCS. No clinical trials for epidural motor cortex stimulation (MCS) or HD-tDCS were found. Parameters of stimulation and also clinical characteristics varied significantly across studies. Three out of eight studies showed larger effects sizes (0.73, 0.88 and 1.86 respectively) for pain reduction. Classical neuropathic pain symptoms such as dysesthesia (defined as an unpleasant burning sensation in response to touch), allodynia (pain due to a non-painful stimulus), pain in paroxysms, location of SCI in thoracic and lumbar segments and pain in the lower limbs seem to be associated with a positive response to neural stimulation. No significant adverse effects were reported in these studies. Chronic pain in SCI is disabling and resistant to common pharmacologic approaches. Electrical and magnetic neural stimulation techniques have been developed to offer a potential tool in the management of these patients. Although some of these techniques are associated with large standardized mean differences to reduce pain, we found an important variability in these results across studies. There is a clear need for the development of methods to decrease treatment variability and increase response to neural stimulation for pain treatment. We discuss potential methods such as neuroimaging or EEG-guided neural stimulation and the development of better surrogate markers of response such as TMS-indexed cortical plasticity. Copyright © 2013. Published by Elsevier Inc.

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Adult and Youth Populations: A Systematic Literature Review and Meta-Analysis

PubMed Central

Leggett, Laura E.; Soril, Lesley J. J.; Coward, Stephanie; Lorenzetti, Diane L.; MacKean, Gail; Clement, Fiona M.

2015-01-01

Background: Between 30% and 60% of individuals with major depressive disorder will have treatment-resistant depression (TRD): depression that does not subside with pharmaceutical treatment. Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for TRD. Objective: To establish the efficacy and optimal protocol for rTMS among adults and youth with TRD. Data Sources: Two systematic reviews were conducted: one to determine the efficacy of rTMS for adults with TRD and another to determine the effectiveness of rTMS for youth with TRD. For adults, MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, and Health Technology Assessment Database were searched from inception until January 10, 2014 with no language restrictions. Terms aimed at capturing the target diagnosis, such as depression and depressive disorder, were combined with terms describing the technology, such as transcranial magnetic stimulation and rTMS. Results were limited to studies involving human participants and designed as a randomized controlled trial. For youth, the search was altered to include youth only (aged 13–25 years) and all study designs. When possible, meta-analysis of response and remission rates was conducted. Study Selection: Seventy-three articles were included in this review: 70 on adult and 3 on youth populations. Results: Meta-analysis comparing rTMS and sham in adults found statistically significant results favoring rTMS for response (RR: 2.35 [95% CI, 1.70–3.25]) and remission (RR: 2.24 [95% CI, 1.53–3.27]). No statistically significant differences were found when comparing high- and low-frequency, unilateral and bilateral, low- and high-intensity rTMS or rTMS and electroconvulsive therapy (ECT). While meta-analysis of results from the youth literature was not possible, the limited evidence base suggests that rTMS may be effective for treating TRD in youth. Conclusions: The evidence available on the use of rTMS for adults with TRD indicates that rTMS is approximately twice as effective as a sham procedure, although the optimal rTMS protocol remains unclear. Evidence also indicates that rTMS is as effective as ECT and appears promising as a treatment for youth with TRD; however, the evidence base is underdeveloped. PMID:27057417

Generation of a Mn(IV)-Peroxo or Mn(III)-Oxo-Mn(III) Species upon Oxygenation of Mono- and Binuclear Thiolate-Ligated Mn(II) Complexes.

PubMed

Lee, Chien-Ming; Wu, Wun-Yan; Chiang, Ming-Hsi; Bohle, D Scott; Lee, Gene-Hsiang

2017-09-05

A thiolate-bridged binuclear complex [PPN] 2 [(Mn II ( TMS PS3)) 2 ] (1, PPN = bis(triphenylphosphine)iminium and TMS PS3H 3 = (2,2',2″-trimercapto-3,3',3″-tris(trimethylsilyl)triphenylphosphine)), prepared from the reaction of MnCl 2 /[PPN]Cl and Li 3 [ TMS PS3], converts into a mononuclear complex [PPN][Mn II ( TMS PS3)(DABCO)] (2) in the presence of excess amounts of DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane). Variable temperature studies of solution containing 1 and DABCO by UV-vis spectroscopy indicate that 1 and 2 exist in significant amounts in equilibrium and mononuclear 2 is favored at low temperature. Treatment of 1 or 2 with the monomeric O 2 -side-on-bound [PPN][Mn IV (O 2 )( TMS PS3)] (3) produces the mono-oxo-bridged dimer [PPN] 2 [(Mn III ( TMS PS3)) 2 (μ-O)] (4). The electrochemistry of 1 and 2 reveals anodic peak(s) for a Mn III/ Mn II redox couple at shifted potentials against Fc/Fc + , indicating that both complexes can be oxidized by dioxygen. The O 2 activation mediated by 1 and 2 is investigated in both solution and the solid state. Microcrystals of 2 rapidly react with air or dry O 2 to generate the Mn(IV)-peroxo 3 in high yield, revealing a solid-to-solid transformation and two-electron reduction of O 2 . Oxygenation of 1 or 2 in solution, however, is affected by diffusion and transient concentration of dioxygen in the two different substrates, leading to generation of 3 and 4 in variable ratios.

Repetitive deep transcranial magnetic stimulation improves verbal fluency and written language in a patient with primary progressive aphasia-logopenic variant (LPPA).

PubMed

Trebbastoni, Alessandro; Raccah, Ruggero; de Lena, Carlo; Zangen, Abraham; Inghilleri, Maurizio

2013-07-01

To date, no therapies are available for the logopenic variant of primary progressive aphasia (LPPA). Even though deep repetitive transcranial magnetic stimulation (rTMS) may improve cognitive functions in some neurodegenerative disorders, no previous studies investigated its effects in patients with LPPA. Our aim was to investigate the effects on cognitive function of high frequency rTMS (hf-rTMS) delivered over the left dorso-lateral prefrontal cortex (DLPFC) through a coil designed for deep rTMS, compared to a SHAM stimulation, in a right-handed patient with LPPA. The patient presented a progressive language impairment (phonological errors in speech and naming, impaired single word retrieval and sentences repetition) and predominant left perisylvian atrophy and hypoperfusion. He received four stimulation cycles (two REAL and two SHAM) each of whom lasted 20 min for 5 consecutive days. Patient's performances in frontal, visuo-spatial and linguistic tasks were evaluated before and after each stimulation session. Test scores after REAL were compared with those obtained at baseline and after SHAM. We found a temporary and highly significant improvement in the linguistic skills (both oral and written tasks) but not in the other cognitive domains tested, after REAL, but not SHAM stimulations. Hf-rTMS delivered over the DLPFC could improve language in LPPA by enhancing long-term potentiation and synaptic plasticity within the stimulated and interconnected areas involved in language network. Our findings might prompt future researches into the feasibility and efficacy of deep hf-rTMS as a therapeutic tool in progressive aphasia syndromes and other neurodegenerative disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Improving the antidepressant efficacy of transcranial magnetic stimulation: Maximizing the number of stimulations and treatment location in treatment resistant depression

PubMed Central

McDonald, William M.; Durkalski, Valerie; Ball, Edward R.; Holtzheimer, Paul E.; Pavlicova, Martina; Lisanby, Sarah H.; Avery, David; Anderson, Berry S.; Nahas, Ziad; Zarkowski, Paul; Sackeim, Harold A.; George, Mark S.

2015-01-01

Objective To assess the efficacy of increasing the number of fast left repetitive transcranial magnetic stimulations (rTMS) (10 Hz @ 120% of motor threshold (MT) over the left dorsolateral prefrontal cortex (DLPFC)) needed to achieve remission in treatment resistant depression (TRD). And, to determine if patients who do not remit to fast left will remit using slow right rTMS (1 Hz @ 120% MT over the right DLPFC). Method Patients were part of a multicenter sham controlled trial investigating the efficacy of fast left rTMS 1. Patients who failed to meet minimal response criteria in the sham controlled study could enroll in this open fast left rTMS study for an additional 3- 6 weeks. Patients who failed to remit to fast left could switch to slow right rTMS for up to four additional weeks. The final outcome measure was remission, defined as a HAM-D score of ≤ 3 or two consecutive HAM-D scores less than 10. Results Forty-three of 141 (30.5%) patients who enrolled in the open phase study eventually met criteria for remission. Patients who remitted during fast left treatment received a mean of 26 active treatments (90,000 pulses). 26% of patients who failed fast left remitted during slow right treatment. Conclusion The total number of rTMS stimulations needed to achieve remission in TRD may be higher than is used in most studies. TRD patients who do not respond to fast left rTMS may remit to slow right rTMS or additional rTMS stimulations. PMID:21898711

A novel coil array for combined TMS/fMRI experiments at 3 T

PubMed Central

Navarro de Lara, Lucia I.; Windischberger, Christian; Kuehne, Andre; Woletz, Michael; Sieg, Jürgen; Bestmann, Sven; Weiskopf, Nikolaus; Strasser, Bernhard; Moser, Ewald

2014-01-01

Purpose To overcome current limitations in combined transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) studies by employing a dedicated coil array design for 3 Tesla. Methods The state‐of‐the‐art setup for concurrent TMS/fMRI is to use a large birdcage head coil, with the TMS between the subject's head and the MR coil. This setup has drawbacks in sensitivity, positioning, and available imaging techniques. In this study, an ultraslim 7‐channel receive‐only coil array for 3 T, which can be placed between the subject's head and the TMS, is presented. Interactions between the devices are investigated and the performance of the new setup is evaluated in comparison to the state‐of‐the‐art setup. Results MR sensitivity obtained at the depth of the TMS stimulation is increased by a factor of five. Parallel imaging with an acceleration factor of two is feasible with low g‐factors. Possible interactions between TMS and the novel hardware were investigated and were found negligible. Conclusion The novel coil array is safe, strongly improves signal‐to‐noise ratio in concurrent TMS/fMRI experiments, enables parallel imaging, and allows for flexible positioning of the TMS on the head while ensuring efficient TMS stimulation due to its ultraslim design. Magn Reson Med 74:1492–1501, 2015. © 2014 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID:25421603

The Effects of rTMS Combined with Motor Training on Functional Connectivity in Alpha Frequency Band.

PubMed

Jin, Jing-Na; Wang, Xin; Li, Ying; Jin, Fang; Liu, Zhi-Peng; Yin, Tao

2017-01-01

It has recently been reported that repetitive transcranial magnetic stimulation combined with motor training (rTMS-MT) could improve motor function in post-stroke patients. However, the effects of rTMS-MT on cortical function using functional connectivity and graph theoretical analysis remain unclear. Ten healthy subjects were recruited to receive rTMS immediately before application of MT. Low frequency rTMS was delivered to the dominant hemisphere and non-dominant hand performed MT over 14 days. The reaction time of Nine-Hole Peg Test and electroencephalography (EEG) in resting condition with eyes closed were recorded before and after rTMS-MT. Functional connectivity was assessed by phase synchronization index (PSI), and subsequently thresholded to construct undirected graphs in alpha frequency band (8-13 Hz). We found a significant decrease in reaction time after rTMS-MT. The functional connectivity between the parietal and frontal cortex, and the graph theory statistics of node degree and efficiency in the parietal cortex increased. Besides the functional connectivity between premotor and frontal cortex, the degree and efficiency of premotor cortex showed opposite results. In addition, the number of connections significantly increased within inter-hemispheres and inter-regions. In conclusion, this study could be helpful in our understanding of how rTMS-MT modulates brain activity. The methods and results in this study could be taken as reference in future studies of the effects of rTMS-MT in stroke patients.

The Origin of Word-related Motor Activity

PubMed Central

Papeo, Liuba; Lingnau, Angelika; Agosta, Sara; Pascual-Leone, Alvaro; Battelli, Lorella; Caramazza, Alfonso

2015-01-01

Conceptual processing of verbs consistently recruits the left posterior middle temporal gyrus (lpMTG). The left precentral motor cortex also responds to verbs, with higher activity for action than nonaction verbs. The early timing of this effect has suggested that motor features of words' meaning are accessed directly, bypassing access to conceptual representations in lpMTG. An alternative hypothesis is that the retrieval of conceptual representations in lpMTG is necessary to drive more specific, motor-related representations in the precentral gyrus. To test these hypotheses, we first showed that repetitive transcranial magnetic stimulation (rTMS) applied to the verb-preferring lpMTG site selectively impoverished the semantic processing of verbs. In a second experiment, rTMS perturbation of lpMTG, relative to no stimulation (no-rTMS), eliminated the action–nonaction verb distinction in motor activity, as indexed by motor-evoked potentials induced in peripheral muscles with single-pulse TMS over the left primary motor cortex. rTMS pertubation of an occipital control site, relative to no-rTMS, did not affect the action–nonaction verb distinction in motor activity, but the verb contrast did not differ reliably from the lpMTG effect. The results show that lpMTG carries core semantic information necessary to drive the activation of specific (motor) features in the precentral gyrus. PMID:24421174

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil.

PubMed

Feifel, David; Pappas, Katherine

2016-10-04

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression. Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.

Cognitive enhancing effects of rTMS administered to the prefrontal cortex in patients with depression: A systematic review and meta-analysis of individual task effects.

PubMed

Martin, Donel M; McClintock, Shawn M; Forster, Jane J; Lo, Tin Yan; Loo, Colleen K

2017-11-01

Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level. A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression. Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47). A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability. © 2017 Wiley Periodicals, Inc.

Transcranial Magnetic Stimulation and Aphasia Rehabilitation

PubMed Central

Naeser, Margaret A.; Martin, Paula I; Ho, Michael; Treglia, Ethan; Kaplan, Elina; Bhashir, Shahid; Pascual-Leone, Alvaro

2013-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been reported to improve naming in chronic stroke patients with nonfluent aphasia since 2005. In Part 1, we review the rationale for applying slow, 1 Hz, rTMS to the undamaged right hemisphere in chronic nonfluent aphasia patients following a left hemisphere stroke; and present a TMS protocol used with these patients that is associated with long-term, improved naming post- TMS. In Part, 2 we present results from a case study with chronic nonfluent aphasia where TMS treatments were followed immediately by speech therapy (constraint-induced language therapy). In Part 3, some possible mechanisms associated with improvement following a series of TMS treatments in stroke patients with aphasia are discussed. PMID:22202188

Assessing TMS-induced D and I waves with spinal H-reflexes.

PubMed

Niemann, Niclas; Wiegel, Patrick; Kurz, Alexander; Rothwell, John C; Leukel, Christian

2018-03-01

Transcranial magnetic stimulation (TMS) of motor cortex produces a series of descending volleys known as D (direct) and I (indirect) waves. In the present study, we questioned whether spinal H-reflexes can be used to dissect D waves and early and late I waves from TMS. We therefore probed H-reflex facilitation at arrival times of D and I waves at the spinal level and thereby changed TMS parameters that have previously been shown to have selective effects on evoked D and different I waves. We changed TMS intensity and current direction and applied a double-pulse paradigm known as short-interval intracortical inhibition (SICI). Experiments were conducted in flexor carpi radialis (FCR) in the arm and soleus (SOL) in the leg. There were two major findings: 1) in FCR, H-reflex facilitation showed characteristic modulations with altered TMS parameters that correspond to the changes of evoked D and I waves; and 2) H-reflexes in SOL did not, possibly because of increased interference from other spinal circuits. Therefore, the most significant outcome of this study is that in FCR, H-reflexes combined with TMS seem to be a useful technique to dissect TMS-induced D and I waves. NEW & NOTEWORTHY Questions that relate to corticospinal function in pathophysiology and movement control demand sophisticated techniques to provide information about corticospinal mechanisms. We introduce a noninvasive electrophysiological technique that may be useful in describing such mechanisms in more detail by dissecting D and I waves from transcranial magnetic stimulation (TMS). Based on the combination of spinal H-reflexes and TMS in the flexor carpi radialis muscle, the technique was shown to measure selective effects on D and I waves from changing TMS parameters.

Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial.

PubMed

Brys, Miroslaw; Fox, Michael D; Agarwal, Shashank; Biagioni, Milton; Dacpano, Geraldine; Kumar, Pawan; Pirraglia, Elizabeth; Chen, Robert; Wu, Allan; Fernandez, Hubert; Wagle Shukla, Aparna; Lou, Jau-Shin; Gray, Zachary; Simon, David K; Di Rocco, Alessandro; Pascual-Leone, Alvaro

2016-11-01

To assess whether multifocal, high-frequency repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and mood symptoms in patients with Parkinson disease (PD). Patients with PD and depression were enrolled in this multicenter, double-blind, sham-controlled, parallel-group study of real or realistic (electric) sham rTMS. Patients were randomized to 1 of 4 groups: bilateral M1 ( + sham dorsolateral prefrontal cortex [DLPFC]), DLPFC ( + sham M1), M1 + DLPFC, or double sham. The TMS course consisted of 10 daily sessions of 2,000 stimuli for the left DLPFC and 1,000 stimuli for each M1 (50 × 4-second trains of 40 stimuli at 10 Hz). Patients were evaluated at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Primary endpoints were changes in motor function assessed with the Unified Parkinson's Disease Rating Scale-III and in mood with the Hamilton Depression Rating Scale at 1 month. Of the 160 patients planned for recruitment, 85 were screened, 61 were randomized, and 50 completed all study visits. Real M1 rTMS resulted in greater improvement in motor function than sham at the primary endpoint (p < 0.05). There was no improvement in mood in the DLPFC group compared to the double-sham group, as well as no benefit to combining M1 and DLPFC stimulation for either motor or mood symptoms. In patients with PD with depression, M1 rTMS is an effective treatment of motor symptoms, while mood benefit after 2 weeks of DLPFC rTMS is not better than sham. Targeting both M1 and DLPFC in each rTMS session showed no evidence of synergistic effects. NCT01080794. This study provides Class I evidence that in patients with PD with depression, M1 rTMS leads to improvement in motor function while DLPFC rTMS does not lead to improvement in depression compared to sham rTMS. © 2016 American Academy of Neurology.

Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: a transcranial magnetic stimulation study.

PubMed

Sun, Peng; Wang, Furong; Wang, Li; Zhang, Yu; Yamamoto, Ryo; Sugai, Tokio; Zhang, Qing; Wang, Zhengda; Kato, Nobuo

2011-11-09

Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism.

Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face

PubMed Central

Pilurzi, G; Hasan, A; Saifee, T A; Tolu, E; Rothwell, J C; Deriu, F

2013-01-01

Previous studies of the cortical control of human facial muscles documented the distribution of corticobulbar projections and the presence of intracortical inhibitory and facilitatory mechanisms. Yet surprisingly, given the importance and precision in control of facial expression, there have been no studies of the afferent modulation of corticobulbar excitability or of the plasticity of synaptic connections in the facial primary motor cortex (face M1). In 25 healthy volunteers, we used standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods to probe motor-evoked potentials (MEPs), short-intracortical inhibition, intracortical facilitation, short-afferent and long-afferent inhibition and paired associative stimulation in relaxed and active depressor anguli oris muscles. Single-pulse TMS evoked bilateral MEPs at rest and during activity that were larger in contralateral muscles, confirming that corticobulbar projection to lower facial muscles is bilateral and asymmetric, with contralateral predominance. Both short-intracortical inhibition and intracortical facilitation were present bilaterally in resting and active conditions. Electrical stimulation of the facial nerve paired with a TMS pulse 5–200 ms later showed no short-afferent inhibition, but long-afferent inhibition was present. Paired associative stimulation tested with an electrical stimulation–TMS interval of 20 ms significantly facilitated MEPs for up to 30 min. The long-term potentiation, evoked for the first time in face M1, demonstrates that excitability of the facial motor cortex is prone to plastic changes after paired associative stimulation. Evaluation of intracortical circuits in both relaxed and active lower facial muscles as well as of plasticity in the facial motor cortex may provide further physiological insight into pathologies affecting the facial motor system. PMID:23297305

Comparison of the induced fields using different coil configurations during deep transcranial magnetic stimulation.

PubMed

Lu, Mai; Ueno, Shoogo

2017-01-01

Stimulation of deeper brain structures by transcranial magnetic stimulation (TMS) plays a role in the study of reward and motivation mechanisms, which may be beneficial in the treatment of several neurological and psychiatric disorders. However, electric field distributions induced in the brain by deep transcranial magnetic stimulation (dTMS) are still unknown. In this paper, the double cone coil, H-coil and Halo-circular assembly (HCA) coil which have been proposed for dTMS have been numerically designed. The distributions of magnetic flux density, induced electric field in an anatomically based realistic head model by applying the dTMS coils were numerically calculated by the impedance method. Results were compared with that of standard figure-of-eight (Fo8) coil. Simulation results show that double cone, H- and HCA coils have significantly deep field penetration compared to the conventional Fo8 coil, at the expense of induced higher and wider spread electrical fields in superficial cortical regions. Double cone and HCA coils have better ability to stimulate deep brain subregions compared to that of the H-coil. In the mean time, both double cone and HCA coils increase risk for optical nerve excitation. Our results suggest although the dTMS coils offer new tool with potential for both research and clinical applications for psychiatric and neurological disorders associated with dysfunctions of deep brain regions, the selection of the most suitable coil settings for a specific clinical application should be based on a balanced evaluation between stimulation depth and focality.

Effects of prefrontal rTMS on autonomic reactions to affective pictures.

PubMed

Berger, Christoph; Domes, Gregor; Balschat, Johannes; Thome, Johannes; Höppner, Jacqueline

2017-02-01

Repetitive transcranial magnetic stimulation (rTMS) can modulate the excitability of stimulated cortical areas, such as prefrontal areas involved in emotion regulation. Low frequency (LF) rTMS is expected to have inhibitory effects on prefrontal regions, and thereby should disinhibit limbic activity, resulting in enhanced emotional and autonomic reactions. For high frequency (HF) rTMS, the opposite pattern might be assumed. The objective of this study was to determine the effects of different rTMS frequencies applied to the right dlPFC on autonomic functions and on emotional perception. In a crossover design, two groups of 20 healthy young women were either stimulated with one session of LF rTMS (1 Hz) or one session of HF rTMS (10 Hz), compared to sham stimulation. We assessed phasic cardiac responses (PCR), skin conductance reactions (SCR), and emotional appraisal of emotional pictures as well as recognition memory after each rTMS application. After LF rTMS, PCR (heart rate deceleration) during presentation of pictures with negative and neutral valence was significantly increased compared to the presentation of positive pictures. In contrast, the modulatory effect of picture valence and arousal on the cardiac orienting response was absent after HF rTMS. Our results suggest that frontal LF rTMS indirectly activates the ANS via inhibition of the right dlPFC activity, likely by enhancing the sensory processing or attention to aversive and neutral stimuli.

Action Verbs and the Primary Motor Cortex: A Comparative TMS Study of Silent Reading, Frequency Judgments, and Motor Imagery

ERIC Educational Resources Information Center

Tomasino, Barbara; Fink, Gereon R.; Sparing, Roland; Dafotakis, Manuel; Weiss, Peter H.

2008-01-01

Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMS[subscript M1] vs. TMS[subscript vertex]) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation…

Transcranial magnetic stimulation promotes the proliferation of dopaminergic neuronal cells in vitro

NASA Astrophysics Data System (ADS)

Zhong, Xiaojing; Luo, Jie; Rastogi, Priyam; Kanthasamy, Anumantha G.; Jiles, David C.; Fellow, IEEE

2018-05-01

Transcranial magnetic stimulation (TMS) is a safe and non-invasive treatment for neurological disorders. TMS has been approved as a treatment for major depressive disorders by the US Food and Drug Administration (FDA) in 2008. Due to the phenomenon of electromagnetic induction, a time-varying magnetic field induces an electric field in the conductive tissues in the brain, TMS has the ability to activate neurons in vivo. However, the effects of the magnetic fields on neurons in cell culture have not been investigated adequately. The magnetic fields affect the neurons when the potential across the neuronal membrane exceeds the threshold which in turn causes an action potential. Based on these theories, we investigated the effects of the magnetic fields generated by a monophasic stimulator with a 70 mm double coil on rat dopaminergic neuronal cell lines (N27). The directions of the magnetic fields in each coil of the double coil oppose each other. The effects of changing the direction of the magnetic field on N27 neurons was also investigated. The results of the experiments showed that both of the fields perpendicular to the coil surface promoted the proliferation of N27 dopaminergic neurons. In order to investigate the gene expression and protein expression affected by TMS, quantitative Polymerase Chain Reaction (qPCR) was used. Here we report changes in glial cell line-derived neurotrophic factor (GDNF) in dopaminergic neuronal cells (N27) after TMS treatment.

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia.

PubMed

Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

2016-01-01

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug's side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy.

Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study.

PubMed

Francis, Michael M; Hummer, Tom A; Vohs, Jenifer L; Yung, Matthew G; Visco, Andrew C; Mehdiyoun, Nikki F; Kulig, Teresa C; Um, Miji; Yang, Ziyi; Motamed, Mehrdad; Liffick, Emily; Zhang, Ying; Breier, Alan

2018-05-31

Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

PubMed

Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

2016-01-13

Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN-DBS with TMS at short (∼ 3 ms) and medium (∼ 23 ms) intervals increased cortical excitability that lasted for up to 45 min, whereas the control condition (fixed latency of 167 ms) had no effects on cortical excitability. This is the first demonstration of associative plasticity in the STN-M1 circuits in PD patients using this novel technique. The potential therapeutic effects of combining DBS and noninvasive cortical stimulation should be investigated further. Copyright © 2016 the authors 0270-6474/16/360397-09$15.00/0.

Systematic Review of Parameters of Stimulation, Clinical Trial Design Characteristics, and Motor Outcomes in Non-Invasive Brain Stimulation in Stroke

PubMed Central

Adeyemo, Bamidele O.; Simis, Marcel; Macea, Debora Duarte; Fregni, Felipe

2012-01-01

Introduction/Objectives: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation are two powerful non-invasive neuromodulatory therapies that have the potential to alter and evaluate the integrity of the corticospinal tract. Moreover, recent evidence has shown that brain stimulation might be beneficial in stroke recovery. Therefore, investigating and investing in innovative therapies that may improve neurorehabilitative stroke recovery are next steps in research and development. Participants/Materials and Methods: This article presents an up-to-date systematic review of the treatment effects of rTMS and tDCS on motor function. A literary search was conducted, utilizing search terms “stroke” and “transcranial stimulation.” Items were excluded if they failed to: (1) include stroke patients, (2) study motor outcomes, or (3) include rTMS/tDCS as treatments. Other exclusions included: (1) reviews, editorials, and letters, (2) animal or pediatric populations, (3) case reports or sample sizes ≤2 patients, and (4) primary outcomes of dysphagia, dysarthria, neglect, or swallowing. Results: Investigation of PubMed English Database prior to 01/01/2012 produced 695 applicable results. Studies were excluded based on the aforementioned criteria, resulting in 50 remaining studies. They included 1314 participants (1282 stroke patients and 32 healthy subjects) evaluated by motor function pre- and post-tDCS or rTMS. Heterogeneity among studies’ motor assessments was high and could not be accounted for by individual comparison. Pooled effect sizes for the impact of post-treatment improvement revealed consistently demonstrable improvements after tDCS and rTMS therapeutic stimulation. Most studies provided limited follow-up for long-term effects. Conclusion: It is apparent from the available studies that non-invasive stimulation may enhance motor recovery and may lead to clinically meaningful functional improvements in the stroke population. Only mild to no adverse events have been reported. Though results have been positive results, the large heterogeneity across articles precludes firm conclusions. PMID:23162477

Controllable pulse parameter transcranial magnetic stimulator with enhanced circuit topology and pulse shaping

NASA Astrophysics Data System (ADS)

Peterchev, Angel V.; DʼOstilio, Kevin; Rothwell, John C.; Murphy, David L.

2014-10-01

Objective. This work aims at flexible and practical pulse parameter control in transcranial magnetic stimulation (TMS), which is currently very limited in commercial devices. Approach. We present a third generation controllable pulse parameter device (cTMS3) that uses a novel circuit topology with two energy-storage capacitors. It incorporates several implementation and functionality advantages over conventional TMS devices and other devices with advanced pulse shape control. cTMS3 generates lower internal voltage differences and is implemented with transistors with a lower voltage rating than prior cTMS devices. Main results. cTMS3 provides more flexible pulse shaping since the circuit topology allows four coil-voltage levels during a pulse, including approximately zero voltage. The near-zero coil voltage enables snubbing of the ringing at the end of the pulse without the need for a separate active snubber circuit. cTMS3 can generate powerful rapid pulse sequences (\\lt 10 ms inter pulse interval) by increasing the width of each subsequent pulse and utilizing the large capacitor energy storage, allowing the implementation of paradigms such as paired-pulse and quadripulse TMS with a single pulse generation circuit. cTMS3 can also generate theta (50 Hz) burst stimulation with predominantly unidirectional electric field pulses. The cTMS3 device functionality and output strength are illustrated with electrical output measurements as well as a study of the effect of pulse width and polarity on the active motor threshold in ten healthy volunteers. Significance. The cTMS3 features could extend the utility of TMS as a research, diagnostic, and therapeutic tool.

Controllable pulse parameter transcranial magnetic stimulator with enhanced circuit topology and pulse shaping

PubMed Central

D’Ostilio, Kevin; Rothwell, John C; Murphy, David L

2014-01-01

Objective This work aims at flexible and practical pulse parameter control in transcranial magnetic stimulation (TMS), which is currently very limited in commercial devices. Approach We present a third generation controllable pulse parameter device (cTMS3) that uses a novel circuit topology with two energy-storage capacitors. It incorporates several implementation and functionality advantages over conventional TMS devices and other devices with advanced pulse shape control. cTMS3 generates lower internal voltage differences and is implemented with transistors with lower voltage rating than prior cTMS devices. Main results cTMS3 provides more flexible pulse shaping since the circuit topology allows four coil-voltage levels during a pulse, including approximately zero voltage. The near-zero coil voltage enables snubbing of the ringing at the end of the pulse without the need for a separate active snubber circuit. cTMS3 can generate powerful rapid pulse sequences (<10 ms inter pulse interval) by increasing the width of each subsequent pulse and utilizing the large capacitor energy storage, allowing the implementation of paradigms such as paired-pulse and quadripulse TMS with a single pulse generation circuit. cTMS3 can also generate theta (50 Hz) burst stimulation with predominantly unidirectional electric field pulses. The cTMS3 device functionality and output strength are illustrated with electrical output measurements as well as a study of the effect of pulse width and polarity on the active motor threshold in 10 healthy volunteers. Significance The cTMS3 features could extend the utility of TMS as a research, diagnostic, and therapeutic tool. PMID:25242286

[Hospital production cost of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression].

PubMed

Etcheverrigaray, F; Bulteau, S; Machon, L O; Riche, V P; Mauduit, N; Tricot, R; Sellal, O; Sauvaget, A

2015-08-01

Repetitive transcranial magnetic stimulation (rTMS) is an effective and well-tolerated treatment in resistant depression with mild to moderate intensity. This indication has not yet been approved in France. The cost and medico-economic value of rTMS in psychiatry remains unknown. The aim of this preliminary study was to assess rTMS cost production analysis as an in-hospital treatment for depression. The methodology, derived from analytical accounts, was validated by a multidisciplinary task force (clinicians, public health doctors, pharmacists, administrative officials and health economist). It was pragmatic, based on official and institutional documentary sources and from field practice. It included equipment, staff, and structure costs, to get an estimate as close to reality as possible. First, we estimated the production cost of rTMS session, based on our annual activity. We then estimated the cost of a cure, which includes 15 sessions. A sensitivity analysis was also performed. The hospital production cost of a cure for treating depression was estimated at € 1932.94 (€ 503.55 for equipment, € 1082.75 for the staff, and € 346.65 for structural expenses). This cost-estimate has resulted from an innovative, pragmatic, and cooperative approach. It is slightly higher but more comprehensive than the costs estimated by the few international studies. However, it is limited due to structure-specific problems and activity. This work could be repeated in other circumstances in order to obtain a more general estimate, potentially helpful for determining an official price for the French health care system. Moreover, budgetary constraints and public health choices should be taken into consideration. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Ionization in liquids: Request for 1992--1993 funding and 1991--1992 progress report

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

Not Available

1992-12-31

Studies of the influence of solvent composition on electron mobility, {mu}{sub e}, which we reported for mixtures of neopentane (NP) and tetramethysilane (TMS) were extended to mixtures of TMS with isooctane (i-octane) or cyclohexane (c-hexane). Whereas our initial TMS /NP study focused on an electron transport regime in which {mu}{sub e} varied only from 67 cm{sup 2}/Vs in NP to 100 cm{sup 2}/Vs in TMS, the more recent studies extended to values of {mu}{sub e} of 7.5 and 0.22 cm{sup 2}/Vs in i-octane and c-hexane, respectively. Whereas a linear dependence of log {mu}{sub e} on solvent composition had been foundmore » in earlier studies of electron transport in mixtures, a negative deviation from this dependence was found in TMS/NP mixtures. In contrast, a positive deviation from linearity was observed in TMS/c-hexane mixtures. Despite the markedly different dependences of {mu}{sub e} on solvent composition for these mixtures, the observed dependences are consistent with the percolation model of electron transport that Schiller has developed.« less

Tri-state high speed rail study : Chicago - Milwaukee - Twin Cities corridor

DOT National Transportation Integrated Search

1991-05-01

This report, the Final Report for the Tri-State Study of High Speed Rail Service, describes the work carried out by TMS/Benesch in analyzing the potential for high speed rail in the Tri-State Corridor. Specifically, the study provides a pre-feasibili...

Meta-Analysis of Oxaliplatin-Based Chemotherapy Combined With Traditional Medicines for Colorectal Cancer

PubMed Central

Chen, Menghua; May, Brian H.; Zhou, Iris W.; Xue, Charlie C. L.; Zhang, Anthony L.

2015-01-01

This meta-analysis evaluates the clinical evidence for the addition of traditional medicines (TMs) to oxaliplatin-based regimens for colorectal cancer (CRC) in terms of tumor response rate (TRR). Eight electronic databases were searched for randomized controlled trials of oxaliplatin-based chemotherapy combined with TMs compared to the same oxaliplatin-based regimen. Data on TRR from 42 randomized controlled trials were analyzed using Review Manager 5.1. Studies were conducted in China or Japan. Publication bias was not evident. The meta-analyses suggest that the combination of the TMs with oxaliplatin-based regimens increased TRR in the palliative treatment of CRC (risk ratio [RR] 1.31 [1.20-1.42], I2 = 0%). Benefits were evident for both injection products (RR 1.36 [1.18-1.57], I2 = 0%) and orally administered TMs (RR 1.27 [1.15-1.41], I2 = 0%). Further sensitivity analysis of specific plant-based TMs found that Paeonia, Curcuma, and Sophora produced consistently higher contributions to the RR results. Compounds in each of these TMs have shown growth-inhibitory effects in CRC cell-line studies. Specific combinations of TMs appeared to produce higher contributions to TRR than the TMs individually. Notable among these was the combination of Hedyotis, Astragalus, and Scutellaria. PMID:26254190

Charting the Functional Relevance of Broca's Area for Visual Word Recognition and Picture Naming in Dutch Using fMRI-Guided TMS

ERIC Educational Resources Information Center

Wheat, Katherine L.; Cornelissen, Piers L.; Sack, Alexander T.; Schuhmann, Teresa; Goebel, Rainer; Blomert, Leo

2013-01-01

Magnetoencephalography (MEG) has shown pseudohomophone priming effects at Broca's area (specifically pars opercularis of left inferior frontal gyrus and precentral gyrus; LIFGpo/PCG) within [approximately]100 ms of viewing a word. This is consistent with Broca's area involvement in fast phonological access during visual word recognition. Here we…

More female patients and fewer stimuli per session are associated with the short-term antidepressant properties of repetitive transcranial magnetic stimulation (rTMS): a meta-analysis of 54 sham-controlled studies published between 1997–2013

PubMed Central

Kedzior, Karina Karolina; Azorina, Valeriya; Reitz, Sarah Kim

2014-01-01

Background Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) appears to have short-term antidepressant properties. The aim of the current study was to update our previous meta-analysis and to investigate factors associated with the antidepressant properties of rTMS. Method Following a systematic literature search conducted in Medline and PsycInfo, N=14 sham-controlled, parallel design studies (published after 2008 to August 2013) that had utilized rTMS of the DLPFC in major depression were included in the current meta-analysis. The sensitivity and moderator analyses also included data from N=40 studies (published in 1997–2008) from our previous meta-analysis. The effect size (Cohen’s d) in each study was the standardized difference in mean depression scores (on Hamilton Depression Rating Scale, Beck Depression Inventory, Montgomery Åsberg Depression Rating Scale) from baseline to final (after last session) in rTMS compared to sham groups. Results According to a random-effects model with inverse-variance weights, depression scores were significantly reduced after rTMS compared to sham in studies published from 2008–2013 based on N=659 patients (overall mean weighted d=−0.42, 95% confidence interval: −0.66, −0.18, P=0.001). Combining studies from our past and current meta-analyses (published in 1997–2013; N=54) revealed that depression was significantly reduced after left-fast (>1 Hz), right-slow (≤1 Hz), and bilateral (or sequential) rTMS of DLPFC compared to sham. Significant antidepressant properties of rTMS were observed in studies with patients who were treatment resistant, unipolar (or bipolar), non-psychotic, medication-free (or started on antidepressants concurrently with rTMS). According to univariate meta-regressions, depression scores were significantly lower in studies with more female patients and fewer stimuli per session. There was little evidence that publication bias occurred in the analysis. Conclusion According to this study, the largest meta-analysis to date, short-term antidepressant properties of rTMS are independent of concurrent antidepressants and might depend on sex and the number of stimuli per session. PMID:24855360

Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study

PubMed Central

2012-01-01

Background About 25% of schizophrenia patients with auditory hallucinations are refractory to pharmacotherapy and electroconvulsive therapy. We conducted a deep transcranial magnetic stimulation (TMS) pilot study in order to evaluate the potential clinical benefit of repeated left temporoparietal cortex stimulation in these patients. The results were encouraging, but a sham-controlled study was needed to rule out a placebo effect. Methods A total of 18 schizophrenic patients with refractory auditory hallucinations were recruited, from Beer Yaakov MHC and other hospitals outpatient populations. Patients received 10 daily treatment sessions with low-frequency (1 Hz for 10 min) deep TMS applied over the left temporoparietal cortex, using the H1 coil at the intensity of 110% of the motor threshold. Procedure was either real or sham according to patient randomization. Patients were evaluated via the Auditory Hallucinations Rating Scale, Scale for the Assessment of Positive Symptoms-Negative Symptoms, Clinical Global Impressions, and Quality of Life Questionnaire. Results In all, 10 patients completed the treatment (10 TMS sessions). Auditory hallucination scores of both groups improved; however, there was no statistical difference in any of the scales between the active and the sham treated groups. Conclusions Low-frequency deep TMS to the left temporoparietal cortex using the protocol mentioned above has no statistically significant effect on auditory hallucinations or the other clinical scales measured in schizophrenic patients. Trial Registration Clinicaltrials.gov identifier: NCT00564096. PMID:22559192

Added value of multiple versus single sessions of repetitive transcranial magnetic stimulation in predicting motor cortex stimulation efficacy for refractory neuropathic pain.

PubMed

Pommier, Benjamin; Quesada, Charles; Fauchon, Camille; Nuti, Christophe; Vassal, François; Peyron, Roland

2018-05-18

OBJECTIVE Selection criteria for offering patients motor cortex stimulation (MCS) for refractory neuropathic pain are a critical topic of research. A single session of repetitive transcranial magnetic stimulation (rTMS) has been advocated for selecting MCS candidates, but it has a low negative predictive value. Here the authors investigated whether multiple rTMS sessions would more accurately predict MCS efficacy. METHODS Patients included in this longitudinal study could access MCS after at least four rTMS sessions performed 3-4 weeks apart. The positive (PPV) and negative (NPV) predictive values of the four rTMS sessions and the correlation between the analgesic effects of the two treatments were assessed. RESULTS Twelve MCS patients underwent an average of 15.9 rTMS sessions prior to surgery; nine of the patients were rTMS responders. Postoperative follow-up was 57.8 ± 15.6 months (mean ± standard deviation). Mean percentage of pain relief (%R) was 21% and 40% after the first and fourth rTMS sessions, respectively. The corresponding mean durations of pain relief were respectively 2.4 and 12.9 days. A cumulative effect of the rTMS sessions was observed on both %R and duration of pain relief (p < 0.01). The %R value obtained with MCS was 35% after 6 months and 43% at the last follow-up. Both the PPV and NPV of rTMS were 100% after the fourth rTMS session (p = 0.0045). A significant correlation was found between %R or duration of pain relief after the fourth rTMS session and %R at the last MCS follow-up (R 2 = 0.83, p = 0.0003). CONCLUSIONS Four rTMS sessions predicted MCS efficacy better than a single session in neuropathic pain patients. Taking into account the cumulative effects of rTMS, the authors found a high-level correlation between the analgesic effects of rTMS and MCS.

Time change of perceptual reversal of ambiguous figures by rTMS.

PubMed

Nojima, K; Ge, S; Katayama, Y; Iramina, K

2010-01-01

The aim of this study was to investigate the effect of stimulus frequency and number of pulses during rTMS (repetitive transcranial magnetic stimulation) on the phenomenon of perceptual reversal. Particularly, we focused on the temporal dynamics of perceptual reversal in the right SPL (superior parietal lobule), using the spinning wheel illusion. We measured the IRT (inter-reversal time) of perceptual reversal. To investigate whether stimulus frequency or the number of pulses is critical for the rTMS effect, we applied the following schedules over the right SPL and the right PTL (posterior temporal lobe): 0.25Hz 60 pulses, 0.25Hz 120pulses, 0.5Hz 120 pulses, and 1Hz 120 pulses biphasic rTMS at 90% of the resting motor threshold. As a control, we included a No-TMS condition. The results showed that rTMS with 0.25Hz 60 pulses over the right SPL caused shorter IRT. There were no significant differences between IRTs for rTMS with 0.25Hz 120 pulses, 0.5Hz 120 pulses or 1Hz 120 pulses over the right SPL. Comparing these results with those of a previous study, we found that an rTMS condition with 60 pulses causes shorter IRT; 240 pulses causes longer IRT; and 120 pulses does not change IRT. Therefore, when applying rTMS over the right SPL, the IRT of perceptual reversal is primarily affected by the number of pulses.

Effect of the stimulus frequency and pulse number of repetitive transcranial magnetic stimulation on the inter-reversal time of perceptual reversal on the right superior parietal lobule

NASA Astrophysics Data System (ADS)

Nojima, Kazuhisa; Ge, Sheng; Katayama, Yoshinori; Ueno, Shoogo; Iramina, Keiji

2010-05-01

The aim of this study is to investigate the effect of the stimulus frequency and pulses number of repetitive transcranial magnetic stimulation (rTMS) on the inter-reversal time (IRT) of perceptual reversal on the right superior parietal lobule (SPL). The spinning wheel illusion was used as the ambiguous figures stimulation in this study. To investigate the rTMS effect over the right SPL during perceptual reversal, 0.25 Hz 60 pulse, 1 Hz 60 pulse, 0.5 Hz 120 pulse, 1 Hz 120 pulse, and 1 Hz 240 pulse biphasic rTMS at 90% of resting motor threshold was applied over the right SPL and the right posterior temporal lobe (PTL), respectively. As a control, a no TMS was also conducted. It was found that rTMS on 0.25 Hz 60 pulse and 1 Hz 60 pulse applied over the right SPL caused shorter IRT. In contrast, it was found that rTMS on 1 Hz 240-pulse applied over the right SPL caused longer IRT. On the other hand, there is no significant difference between IRTs when the rTMS on 0.5 Hz 120 pulse and 1 Hz 120 pulse were applied over the right SPL. Therefore, the applying of rTMS over the right SPL suggests that the IRT of perceptual reversal is effected by the rTMS conditions such as the stimulus frequency and the number of pulses.

Detection of Bacillus and Stenotrophomonas species growing in an organic acid and endocrine-disrupting chemical-rich environment of distillery spent wash and its phytotoxicity.

PubMed

Chandra, Ram; Kumar, Vineet

2017-01-01

Sugarcane molasses-based distillery spent wash (DSW) is well known for its toxicity and complex mixture of various recalcitrant organic pollutants with acidic pH, but the chemical nature of these pollutants is unknown. This study revealed the presence of toxic organic acids (butanedioic acid bis(TMS)ester; 2-hydroxysocaproic acid; benzenepropanoic acid, α-[(TMS)oxy], TMS ester; vanillylpropionic acid, bis(TMS)), and other recalcitrant organic pollutants (2-furancarboxylic acid, 5-[[(TMS)oxy] methyl], TMS ester; benzoic acid 3-methoxy-4-[(TMS)oxy], TMS ester; and tricarballylic acid 3TMS), which are listed as endocrine-disrupting chemicals. In addition, several major heavy metals were detected, including Fe (163.947), Mn (4.556), Zn (2.487), and Ni (1.175 mg l -1 ). Bacterial community analysis by restriction fragment length polymorphism revealed that Bacillus and Stenotrophomonas were dominant autochthonous bacterial communities belonging to the phylum Firmicutes and γ-Proteobacteria, respectively. The presence of Bacillus and Stenotrophomonas species in highly acidic environments indicated its broad range adaptation. These findings indicated that these autochthonous bacterial communities were pioneer taxa for in situ remediation of this hazardous waste during ecological succession. Further, phytotoxicity assay of DSW with Phaseolus mungo L. and Triticum aestivum revealed that T. aestivum was more sensitive than P. mungo L. in the seed germination test. The results of this study may be useful for monitoring and toxicity assessment of sugarcane molasses-based distillery waste at disposal sites.

Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case.

PubMed

Phielipp, Nicolás M; Saha, Utpal; Sankar, Tejas; Yugeta, Akihiro; Chen, Robert

2017-06-01

To evaluate the safety of repetitive transcranial magnetic stimulation (rTMS) in patients with implanted subdural cortical electrodes. We performed ex-vivo experiments to test the temperature, displacement and current induced in the electrodes with single pulse transcranial magnetic stimulation (TMS) from 10 to 100% of stimulator output and tested a typical rTMS protocol used in a clinical setting. We then used rTMS to the motor cortex to treat a patient with refractory post-herpetic neuralgia who had previously been implanted with a subdural motor cortical electrode for pain management. The rTMS protocol consisted of ten sessions of 2000 stimuli at 20Hz and 90% of resting motor threshold. The ex-vivo study showed an increase in the coil temperature of 2°C, a maximum induced charge density of 30.4μC/cm 2 /phase, and no electrode displacement with TMS. There was no serious adverse effect associated with rTMS treatment of the patient. Cortical tremor was observed in the intervals between trains of stimuli during one treatment session. TMS was safe in a patient with implanted Medtronic Resume II electrode (model 3587A) subdural cortical electrode. TMS may be used as a therapeutic, diagnostic or research tool in patients this type of with implanted cortical electrodes. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Training voluntary motor suppression with real-time feedback of motor evoked potentials.

PubMed

Majid, D S Adnan; Lewis, Christina; Aron, Adam R

2015-05-01

Training people to suppress motor representations voluntarily could improve response control. We evaluated a novel training procedure of real-time feedback of motor evoked potentials (MEPs) generated by transcranial magnetic stimulation (TMS) over motor cortex. On each trial, a cue instructed participants to use a mental strategy to suppress a particular finger representation without overt movement. A single pulse of TMS was delivered over motor cortex, and an MEP-derived measure of hand motor excitability was delivered visually to the participant within 500 ms. In experiment 1, we showed that participants learned to reduce the excitability of a particular finger beneath baseline (selective motor suppression) within 30 min of practice. In experiment 2, we performed a double-blind study with 2 training groups (1 with veridical feedback and 1 with matched sham feedback) to show that selective motor suppression depends on the veridical feedback itself. Experiment 3 further demonstrated the importance of veridical feedback by showing that selective motor suppression did not arise from mere mental imagery, even when incentivized with reward. Thus participants can use real-time feedback of TMS-induced MEPs to discover an effective mental strategy for selective motor suppression. This high-temporal-resolution, trial-by-trial-feedback training method could be used to help people better control response tendencies and may serve as a potential therapy for motor disorders such as Tourette's and dystonia. Copyright © 2015 the American Physiological Society.

The efficacy of transcranial magnetic stimulation on migraine: a meta-analysis of randomized controlled trails.

PubMed

Lan, Lihuan; Zhang, Xiaoni; Li, Xiangpen; Rong, Xiaoming; Peng, Ying

2017-08-22

As a non-invasive therapy, whether transcranial magnetic stimulation (TMS) is effective on migraine. This article was aimed to assess the efficacy of TMS on migraine based on randomized controlled trails (RCTs). We searched PubMed, Embase and Cochrane Library electronic databases for published studies which compared TMS group with sham group, conducted a meta-analysis of all RCTs. Five studies, consisting of 313 migraine patients, were identified. Single-pulse transcranial magnetic stimulation is effective for the acute treatment of migraine with aura after the first attack (p = 0.02). And, the efficacy of TMS on chronic migraine was not significant (OR 2.93; 95% CI 0.71-12.15; p = 0.14). TMS is effective for migraine based on the studies included in the article.

FDTD-based Transcranial Magnetic Stimulation model applied to specific neurodegenerative disorders.

PubMed

Fanjul-Vélez, Félix; Salas-García, Irene; Ortega-Quijano, Noé; Arce-Diego, José Luis

2015-01-01

Non-invasive treatment of neurodegenerative diseases is particularly challenging in Western countries, where the population age is increasing. In this work, magnetic propagation in human head is modelled by Finite-Difference Time-Domain (FDTD) method, taking into account specific characteristics of Transcranial Magnetic Stimulation (TMS) in neurodegenerative diseases. It uses a realistic high-resolution three-dimensional human head mesh. The numerical method is applied to the analysis of magnetic radiation distribution in the brain using two realistic magnetic source models: a circular coil and a figure-8 coil commonly employed in TMS. The complete model was applied to the study of magnetic stimulation in Alzheimer and Parkinson Diseases (AD, PD). The results show the electrical field distribution when magnetic stimulation is supplied to those brain areas of specific interest for each particular disease. Thereby the current approach entails a high potential for the establishment of the current underdeveloped TMS dosimetry in its emerging application to AD and PD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Corticospinal Excitability in Children with Congenital Hemiparesis

PubMed Central

Chen, Chao-Ying; Rich, Tonya L.; Cassidy, Jessica M.; Gillick, Bernadette T.

2016-01-01

Transcranial magnetic stimulation (TMS) can be used as an assessment or intervention to evaluate or influence brain activity in children with hemiparetic cerebral palsy (CP) commonly caused by perinatal stroke. This communication report analyzed data from two clinical trials using TMS to assess corticospinal excitability in children and young adults with hemiparetic CP. The results of this communication revealed a higher probability of finding a motor evoked potential (MEP) on the non-lesioned hemisphere compared to the lesioned hemisphere (p = 0.005). The resting motor threshold (RMT) was lower on the non-lesioned hemisphere than the lesioned hemisphere (p = 0.013). There was a significantly negative correlation between age and RMT (rs = −0.65, p = 0.003). This communication provides information regarding MEP responses, motor thresholds (MTs) and the association with age during TMS assessment in children with hemiparetic CP. Such findings contribute to the development of future pediatric studies in neuroplasticity and neuromodulation to influence motor function and recovery after perinatal stroke. PMID:27775599

1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial.

PubMed

Landgrebe, Michael; Hajak, Göran; Wolf, Stefan; Padberg, Frank; Klupp, Philipp; Fallgatter, Andreas J; Polak, Thomas; Höppner, Jacqueline; Haker, Rene; Cordes, Joachim; Klenzner, Thomas; Schönfeldt-Lecuona, Carlos; Kammer, Thomas; Graf, Erika; Koller, Michael; Kleinjung, Tobias; Lehner, Astrid; Schecklmann, Martin; Pöppl, Timm B; Kreuzer, Peter; Frank, Elmar; Langguth, Berthold

Chronic tinnitus is a frequent, difficult to treat disease with high morbidity. This multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus. Tinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment. A total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by -0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: -1.0; 95.19% confidence interval: -3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups. Real 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question. Controlled Trials: http://www.isrctn.com/ISRCTN89848288. Copyright © 2017 Elsevier Inc. All rights reserved.

Electrophysiological evidence of cerebellar fiber system involvement in the Miller Fisher syndrome.

PubMed

Lo, Y L; Fook-Chong, S; Chan, L L; Ong, W Y; Ratnagopal, P

2010-01-15

In the Miller Fisher syndrome (MFS), ataxia may be due involvement of Ia afferents and the cerebellum. Transcranial magnetic stimulation (TMS) over the cerebellum is known to interfere transiently with normal function. In this study, we utilized a previously described TMS protocol over the cerebellum in combination with ballistic movements to investigate cerebellar dysfunction in MFS patients. The agonist (biceps) reaction time in MFS patients during a motor cancellation task was not significantly reduced during the initial TMS study. However, during the repeat TMS study, significant reduction was seen for all patients, in tandem with clinical recovery. There was significant correlation between anti-GQ1b IgG titers and change in agonist reaction time between the initial and repeat TMS studies. TMS likely affected horizontally orientated parallel fibers in the cerebellar molecular layer. During disease onset, antibody binding may have interfered with facilitation of reaction time during motor cancellation tasks seen in normal subjects. Normalization of reaction time facilitation corresponded to resolution of antibody-mediated interference in the molecular layer. Our study has provided evidence suggesting parallel fiber involvement in MFS, and suggested a role of anti-GQ1b IgG antibody in these changes.

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers.

PubMed

Li, Xingbao; Sahlem, Gregory L; Badran, Bashar W; McTeague, Lisa M; Hanlon, Colleen A; Hartwell, Karen J; Henderson, Scott; George, Mark S

2017-12-01

Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue-elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub-cortical neural activity in non-treatment seeking nicotine-dependent participants. We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s-on, 10 s-off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session. A total of 11 non-treatment seeking nicotine-dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS. This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers. rTMS may exert its anti-craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788-794). © 2017 American Academy of Addiction Psychiatry.

Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study.

PubMed

Jung, JeYoung; Bungert, Andreas; Bowtell, Richard; Jackson, Stephen R

2016-01-01

A common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation. Thirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants. Vertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted. The results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of Hesel-coil deep transcranial magnetic stimulation for depression - a systematic review.

PubMed

Nordenskjöld, Axel; Mårtensson, Björn; Pettersson, Agneta; Heintz, Emelie; Landén, Mikael

2016-10-01

One third of the depressed patients are not improved by antidepressant drugs and psychological treatments, and there is a need for additional treatments. Repetitive transcranial magnetic stimulation (rTMS) is being developed towards an alternative in treatment-resistant depression. Deep transcranial stimulation (dTMS) with the Hesel-coil (H-coil) is a further development of rTMS aiming to enhance the effect by getting the magnetic pulses to penetrate deeper into the brain. This report aims to assess the evidence-base for dTMS for depression. The report also includes an assessment of the ethical and economic aspects involved. A systematic review of the effects of H-coil dTMS on depression was conducted and the scientific support was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Only one controlled study was identified. In the sham-controlled randomized study, 212 participants with major depression that had not responded to antidepressant medication were enrolled. A two-point superiority in Hamilton Depression Rating Scale was observed in the dTMS arm vs the sham-arm at 4 weeks, but the difference was not statistically significant. No serious adverse events were reported apart from rare cases of epileptic seizures. The existing scientific support for H-coil dTMS therapy for depression is insufficient. The clinical implication is that the use of dTMS in depression should be restricted to the framework of clinical trials pending further studies. Fortunately, additional studies are underway and the evidence base should presumably improve over the next several years.

Effects of Hesel-coil deep transcranial magnetic stimulation for depression – a systematic review

PubMed Central

Nordenskjöld, Axel; Mårtensson, Björn; Pettersson, Agneta; Heintz, Emelie; Landén, Mikael

2016-01-01

Abstract Background: One third of the depressed patients are not improved by antidepressant drugs and psychological treatments, and there is a need for additional treatments. Repetitive transcranial magnetic stimulation (rTMS) is being developed towards an alternative in treatment-resistant depression. Deep transcranial stimulation (dTMS) with the Hesel-coil (H-coil) is a further development of rTMS aiming to enhance the effect by getting the magnetic pulses to penetrate deeper into the brain. Aims: This report aims to assess the evidence-base for dTMS for depression. The report also includes an assessment of the ethical and economic aspects involved. Methods: A systematic review of the effects of H-coil dTMS on depression was conducted and the scientific support was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results: Only one controlled study was identified. In the sham-controlled randomized study, 212 participants with major depression that had not responded to antidepressant medication were enrolled. A two-point superiority in Hamilton Depression Rating Scale was observed in the dTMS arm vs the sham-arm at 4 weeks, but the difference was not statistically significant. No serious adverse events were reported apart from rare cases of epileptic seizures. Conclusions: The existing scientific support for H-coil dTMS therapy for depression is insufficient. The clinical implication is that the use of dTMS in depression should be restricted to the framework of clinical trials pending further studies. Fortunately, additional studies are underway and the evidence base should presumably improve over the next several years. PMID:27093104

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving.

PubMed

Li, Xingbao; Hartwell, Karen J; Owens, Max; Lematty, Todd; Borckardt, Jeffrey J; Hanlon, Colleen A; Brady, Kathleen T; George, Mark S

2013-04-15

Repetitive transcranial magnetic stimulation (rTMS) can noninvasively stimulate the brain and transiently amplify or block behaviors mediated through a region. We hypothesized that a single high-frequency rTMS session over the left dorsolateral prefrontal cortex (DLPFC) would reduce cue craving for cigarettes compared with a sham TMS session. Sixteen non-treatment-seeking, nicotine-dependent participants were randomized to receive either real high-frequency rTMS (10 Hz, 100% resting motor threshold, 5-sec on, 10-sec off for 15 min; 3000 pulses) or active sham (eSham) TMS over the DLPFC in two visits with 1 week between visits. The participants received cue exposure before and after rTMS and rated their craving after each block of cue presentation. Stimulation of the left DLFPC with real, but not sham, rTMS reduced craving significantly from baseline (64.1±5.9 vs. 45.7±6.4, t = 2.69, p = .018). When compared with neutral cue craving, the effect of real TMS on cue craving was significantly greater than the effect of sham TMS (12.5±10.4 vs. -9.1±10.4; t = 2.07, p = .049). More decreases in subjective craving induced by TMS correlated positively with higher Fagerström Test for Nicotine Dependence score (r = .58, p = .031) and more cigarettes smoked per day (r = .57, p = .035). One session of high-frequency rTMS (10 Hz) of the left DLPFC significantly reduced subjective craving induced by smoking cues in nicotine-dependent participants. Additional studies are needed to explore rTMS as an aid to smoking cessation. Copyright © 2013 Society of Biological Psychiatry. All rights reserved.

Transcranial Magnetic Stimulation (TMS) as a Tool for Early Diagnosis and Prognostication in Cortico-Basal Ganglia Degeneration (CBD) Syndromes: Review of Literature and Case Report.

PubMed

Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Nagaraju, B C

2016-01-01

Cortico basal degeneration (CBD) of the brain is a rare progressive neurodegenerative disease which encompasses unique neuropsychiatric manifestations. Early diagnosis is essential for initiating proper treatment and favorable outcome. Transcranial Magnetic Stimulation (TMS), a well-known technique for assessment of cortical excitatory and inhibitory properties. It was suggested that in a degenerative disease like CBD which involves the cortex as well as the subcortical structures, comparing both hemispheres, a differential pattern in TMS can be obtained which would help in early identification, prognostication and early therapeutic intervention. We describe a case of CBD with corroborative clinical and imaging picture wherein single pulse TMS was used over both the hemispheres measuring the following parameters of interest which included: Motor Threshold (MT), Central Motor Conduction Time (CMCT) and Silent Period (SP). Differential patterns of MT, CMCT and SP was obtained by stimulating over both the hemispheres with the affected hemisphere showing significantly reduced MT and prolonged CMCT implying early impairment of cortical and subcortical structures thereby revealing the potential application of TMS being utilized in a novel way for early detection and prognostication in CBD syndromes.

Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease

PubMed Central

Brys, Miroslaw; Fox, Michael D.; Agarwal, Shashank; Biagioni, Milton; Dacpano, Geraldine; Kumar, Pawan; Pirraglia, Elizabeth; Chen, Robert; Wu, Allan; Fernandez, Hubert; Shukla, Aparna Wagle; Lou, Jau-Shin; Gray, Zachary; Simon, David K.; Di Rocco, Alessandro

2016-01-01

Objective: To assess whether multifocal, high-frequency repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and mood symptoms in patients with Parkinson disease (PD). Methods: Patients with PD and depression were enrolled in this multicenter, double-blind, sham-controlled, parallel-group study of real or realistic (electric) sham rTMS. Patients were randomized to 1 of 4 groups: bilateral M1 ( + sham dorsolateral prefrontal cortex [DLPFC]), DLPFC ( + sham M1), M1 + DLPFC, or double sham. The TMS course consisted of 10 daily sessions of 2,000 stimuli for the left DLPFC and 1,000 stimuli for each M1 (50 × 4-second trains of 40 stimuli at 10 Hz). Patients were evaluated at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Primary endpoints were changes in motor function assessed with the Unified Parkinson's Disease Rating Scale-III and in mood with the Hamilton Depression Rating Scale at 1 month. Results: Of the 160 patients planned for recruitment, 85 were screened, 61 were randomized, and 50 completed all study visits. Real M1 rTMS resulted in greater improvement in motor function than sham at the primary endpoint (p < 0.05). There was no improvement in mood in the DLPFC group compared to the double-sham group, as well as no benefit to combining M1 and DLPFC stimulation for either motor or mood symptoms. Conclusions: In patients with PD with depression, M1 rTMS is an effective treatment of motor symptoms, while mood benefit after 2 weeks of DLPFC rTMS is not better than sham. Targeting both M1 and DLPFC in each rTMS session showed no evidence of synergistic effects. ClinicalTrials.gov identifier: NCT01080794. Classification of evidence: This study provides Class I evidence that in patients with PD with depression, M1 rTMS leads to improvement in motor function while DLPFC rTMS does not lead to improvement in depression compared to sham rTMS. PMID:27708129

Meta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia

PubMed Central

Freitas, Catarina; Fregni, Felipe; Pascual-Leone, Alvaro

2009-01-01

Background A growing body of evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can alleviate negative and positive symptoms of refractory schizophrenia. However, trials to date have been small and results are mixed. Methods We performed meta-analyses of all prospective studies of the therapeutic application of rTMS in refractory schizophrenia assessing the effects of high-frequency rTMS to the left dorsolateral prefrontal cortex (DLPFC) to treat negative symptoms, and low-frequency rTMS to the left temporo-parietal cortex (TPC) to treat auditory hallucinations (AH) and overall positive symptoms. Results When analyzing controlled (active arms) and uncontrolled studies together, the effect sizes showed significant and moderate effects of rTMS on negative and positive symptoms (based on PANSS-N or SANS, and PANSS-P or SAPS, respectively). However, the analysis for the sham-controlled studies revealed a small non-significant effect size for negative (0.27, p=0.417) and for positive symptoms (0.17, p=0.129). When specifically analyzing AH (based on AHRS, HCS or SAH), the effect size for the sham-controlled studies was large and significant (1.04; p=0.002). Conclusions These meta-analyses support the need for further controlled, larger trials to assess the clinical efficacy of rTMS on negative and positive symptoms of schizophrenia, while suggesting the need for exploration for alternative stimulation protocols. PMID:19138833

Comparison of the two cerebral hemispheres in inhibitory processes operative during movement preparation

PubMed Central

Klein, Pierre-Alexandre; Duque, Julie; Labruna, Ludovica; Ivry, Richard B.

2015-01-01

Neuroimaging and neuropsychological studies suggest that in right-handed individuals, the left hemisphere plays a dominant role in praxis, relative to the right hemisphere. However hemispheric asymmetries assessed with transcranial magnetic stimulation (TMS) has not shown consistent differences in corticospinal (CS) excitability of the two hemispheres during movements. In the current study, we systematically explored hemispheric asymmetries in inhibitory processes that are manifest during movement preparation and initiation. Single-pulse TMS was applied over the left or right primary motor cortex (M1LEFT and M1RIGHT, respectively) to elicit motor-evoked potentials (MEPs) in the contralateral hand while participants performed a two-choice reaction time task requiring a cued movement of the left or right index finger. In Experiments 1 and 2, TMS probes were obtained during a delay period following the presentation of the preparatory cue that provided partial or full information about the required response. MEPs were suppressed relative to baseline regardless of whether they were elicited in a cued or uncued hand. Importantly, the magnitude of these inhibitory changes in CS excitability was similar when TMS was applied over M1LEFT or M1RIGHT, irrespective of the amount of information carried by the preparatory cue. In Experiment 3, there was no preparatory cue and TMS was applied at various time points after the imperative signal. When CS excitability was probed in the cued effector, MEPs were initially inhibited and then rose across the reaction time interval. This function was similar for M1LEFT and M1RIGHT TMS. When CS excitability was probed in the uncued effector, MEPs remained inhibited throughout the RT interval. However, MEPs in right FDI became more inhibited during selection and initiation of a left hand movement, whereas MEPs in left FDI remained relatively invariant across RT interval for the right hand. In addition to these task-specific effects, there was a global difference in CS excitability across experiments between the two hemispheres. When the intensity of stimulation was set to 115% of the resting threshold, MEPs were larger when the TMS probe was applied over the M1LEFT than over M1RIGHT. In summary, while the latter result suggests that M1LEFT is more excitable than M1RIGHT, the recruitment of preparatory inhibitory mechanisms is similar within the two cerebral hemispheres. PMID:26458519

Comparison of the induced fields using different coil configurations during deep transcranial magnetic stimulation

PubMed Central

Ueno, Shoogo

2017-01-01

Stimulation of deeper brain structures by transcranial magnetic stimulation (TMS) plays a role in the study of reward and motivation mechanisms, which may be beneficial in the treatment of several neurological and psychiatric disorders. However, electric field distributions induced in the brain by deep transcranial magnetic stimulation (dTMS) are still unknown. In this paper, the double cone coil, H-coil and Halo-circular assembly (HCA) coil which have been proposed for dTMS have been numerically designed. The distributions of magnetic flux density, induced electric field in an anatomically based realistic head model by applying the dTMS coils were numerically calculated by the impedance method. Results were compared with that of standard figure-of-eight (Fo8) coil. Simulation results show that double cone, H- and HCA coils have significantly deep field penetration compared to the conventional Fo8 coil, at the expense of induced higher and wider spread electrical fields in superficial cortical regions. Double cone and HCA coils have better ability to stimulate deep brain subregions compared to that of the H-coil. In the mean time, both double cone and HCA coils increase risk for optical nerve excitation. Our results suggest although the dTMS coils offer new tool with potential for both research and clinical applications for psychiatric and neurological disorders associated with dysfunctions of deep brain regions, the selection of the most suitable coil settings for a specific clinical application should be based on a balanced evaluation between stimulation depth and focality. PMID:28586349

Interventional repetitive I-wave transcranial magnetic stimulation (TMS): the dimension of stimulation duration.

PubMed

Murray, Lynda M; Nosaka, Kazunori; Thickbroom, Gary W

2011-10-01

A range of transcranial magnetic stimulation (TMS) techniques are now available to modulate human corticomotor excitability and plasticity. One presumably critical aspect of these interventions is their duration of application. In the current study, we investigated whether doubling the duration of an intervention would offer any additional benefit, or invoke self-limiting mechanisms controlling corticomotor excitability or synaptic plasticity. We compared (in a cross-over design) corticomotor excitability (to the first dorsal interosseous muscle) during and after a 15-minute (I15) and 30-minute (I30) TMS intervention targeting indirect (I-) wave interaction (iTMS). The interventions consisted of equi-intensity paired stimuli with an interpulse interval (IPI) of 1.5 milliseconds, corresponding to I-wave periodicity, delivered at a frequency of 0.2 Hz. During both the I15 and I30 interventions, paired-pulse (I-wave) motor evoked potential (iMEP) amplitude significantly increased (by 98.3% and 120.6%, respectively, last versus first minute, P = .001). The increase for I30 occurred in the first 15 minutes, and there was no further change during the remainder of the intervention. Both interventions were equally effective overall. Postintervention, single-pulse MEP amplitude increased by a mean of 91% and 106% (I15 and I30, respectively, P < .01) with no significant difference between interventions. We conclude that repetitive iTMS can increase corticomotor excitability after a relatively short intervention period of stimulation, and that a longer stimulation period has no additional benefit or detriment, perhaps as a result of the action of regulatory mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS.

PubMed

Cheeran, Binith; Talelli, Penelope; Mori, Francesco; Koch, Giacomo; Suppa, Antonio; Edwards, Mark; Houlden, Henry; Bhatia, Kailash; Greenwood, Richard; Rothwell, John C

2008-12-01

The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism (BDNF Val66Met) in the normal population that is associated with differences in hippocampal volume and episodic memory. It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task. Here we extend these studies by using new non-invasive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest. We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism. Val66Met carriers were matched with Val66Val individuals and tested on the following protocols: continuous and intermittent theta burst TMS; median nerve paired associative stimulation; and homeostatic plasticity in the TDCS/1 Hz rTMS model. The response of Met allele carriers differed significantly in all protocols compared with the response of Val66Val individuals. We suggest that this is due to the effect of BNDF on the susceptibility of synapses to undergo LTP/LTD. The circuits tested here are implicated in the pathophysiology of movement disorders such as dystonia and are being assessed as potential new targets in the treatment of stroke. Thus the polymorphism may be one factor that influences the natural response of the brain to injury and disease.

Human dorsolateral prefrontal cortex is involved in visual search for conjunctions but not features: a theta TMS study.

PubMed

Kalla, Roger; Muggleton, Neil G; Cowey, Alan; Walsh, Vincent

2009-10-01

Functional neuroimaging studies have shown that the detection of a target defined by more than one feature (for example, a conjunction of colour and orientation) amongst distractors is associated with the activation of a network of brain areas. Dorsolateral prefrontal cortex (DLPFC), along with areas such as the frontal eye fields (FEF) and posterior parietal cortex (PPC), is a component of this network. While transcranial magnetic stimulation (TMS) had shown that both FEF and PPC are necessary for, and not just correlated with, successful conjunction search, this is not the case for DLPFC. To test the hypothesis that this area is also necessary for efficient conjunction search, TMS was applied over DLPFC and the effects on conjunction and feature (in this case colour) search performance compared with those when TMS was delivered over area MT/V5 and a vertex control stimulation condition. DLPFC TMS impaired performance on the conjunction search task but was without effect on feature search, similar to findings when TMS is delivered over PPC or FEF. Vertex TMS had no effects whereas MT/V5 TMS significantly improved performance with a time course that may indicate that this was due to modulation of V4 activity. These findings illustrate that, like FEF and PPC, DLPFC is necessary for fully effective conjunction visual search performance.

The Neuroprotective Mechanism of Low-Frequency rTMS on Nigral Dopaminergic Neurons of Parkinson's Disease Model Mice

PubMed Central

Dong, Qiaoyun; Wang, Yanyong; Gu, Ping; Shao, Rusheng; Zhao, Li; Liu, Xiqi; Wang, Zhanqiang; Wang, Mingwei

2015-01-01

Background. Parkinson's disease is a neurodegenerative disease in elder people, pathophysiologic basis of which is the severe deficiency of dopamine in the striatum. The purpose of the present study was to evaluate the neuroprotective effect of low-frequency rTMS on Parkinson's disease in model mice. Methods. The effects of low-frequency rTMS on the motor function, cortex excitability, neurochemistry, and neurohistopathology of MPTP-induced Parkinson's disease mice were investigated through behavioral detection, electrophysiologic technique, high performance liquid chromatography-electrochemical detection, immunohistochemical staining, and western blot. Results. Low-frequency rTMS could improve the motor coordination impairment of Parkinson's disease mice: the resting motor threshold significantly decreased in the Parkinson's disease mice; the degeneration of nigral dopaminergic neuron and the expression of tyrosine hydroxylase were significantly improved by low-frequency rTMS; moreover, the expressions of brain derived neurotrophic factor and glial cell line derived neurotrophic factor were also improved by low-frequency rTMS. Conclusions. Low-frequency rTMS had a neuroprotective effect on the nigral dopaminergic neuron which might be due to the improved expressions of brain derived neurotrophic factor and glial cell line-derived neurotrophic factor. The present study provided a theoretical basis for the application of low-frequency rTMS in the clinical treatment and recovery of Parkinson's disease. PMID:25883828

Importance and Difficulties of Pursuing rTMS Research in Acute Stroke

PubMed Central

Chappuis, Diane M.; Finkelstein, Marsha J.; Frost, Kate L.; Leuty, Lynette K.; McNulty, Allison L.; Oddsson, Lars I. E.; Seifert, Erin M.; Kimberley, Teresa J.

2017-01-01

Abstract Although much research has been done on repetitive transcranial magnetic stimulation (rTMS) in chronic stroke, only sparse research has been done in acute stroke despite the particularly rich potential for neuroplasticity in this stage. We attempted a preliminary clinical trial in one active, high-quality inpatient rehabilitation facility (IRF) in the -United States. But after enrolling only 4 patients in the grant period, the study was stopped because of low enrollment. The purpose of this paper is to offer a perspective describing the important physiologic rationale for including rTMS in the early phase of stroke, the reasons for our poor patient enrollment in our attempted study, and recommendations to help future studies succeed. We conclude that, if scientists and clinicians hope to enhance stroke outcomes, more attention must be directed to leveraging conventional rehabilitation with neuromodulation in the acute phase of stroke when the capacity for neuroplasticity is optimal. Difficulties with patient enrollment must be addressed by reassessing traditional inclusion and exclusion criteria. Factors that shorten patients’ length of stay in the IRF must also be reassessed at all policy-making levels to make ethical decisions that promote higher functional outcomes while retaining cost consciousness. PMID:28426872

Effects of lacosamide and carbamazepine on human motor cortex excitability: a double-blind, placebo-controlled transcranial magnetic stimulation study.

PubMed

Lang, Nicolas; Rothkegel, Holger; Peckolt, Hannes; Deuschl, Günther

2013-11-01

Lacosamide (LCM) and carbamazepine (CBZ) are antiepileptic drugs both acting on neuronal voltage-gated sodium channels. Patch-clamp studies demonstrated significant differences in how LCM and CBZ affect neuronal membrane excitability. Despite valuable information patch-clamp studies provide, they also comprise some constraints. For example, little is known about effects of LCM on intracortical synaptic excitability. In contrast, transcranial magnetic stimulation (TMS) can describe drug-induced changes at the system level of the human cerebral cortex. The present study was designed to explore dose-depended effects of LCM and effects of CBZ on motor cortex excitability with TMS in a randomized, double-blind, placebo-controlled crossover trial in healthy human subjects. Subjects received 600 mg CBZ, 200 mg LCM, 400 mg LCM or placebo preceding TMS measurements. Compared to placebo, TMS motor thresholds were significantly increased after carbamazepine and lacosamide, with a trend for a dose dependent effect of lacosamide. Both, carbamazepine and lacosamide did not affect TMS parameters of intracortical synaptic excitability. TMS measurements suggest that lacosamide and carbamazepine predominantly act on neuronal membrane excitability. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia

PubMed Central

Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

2016-01-01

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug’s side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy. PMID:27891079

Number of pulses or number of sessions? An open-label study of trajectories of improvement for once-vs. twice-daily dorsomedial prefrontal rTMS in major depression.

PubMed

Schulze, Laura; Feffer, Kfir; Lozano, Christopher; Giacobbe, Peter; Daskalakis, Zafiris J; Blumberger, Daniel M; Downar, Jonathan

Repetitive transcranial magnetic stimulation (rTMS) shows efficacy in the treatment of major depressive episodes (MDEs), but can require ≥4-6 weeks for maximal effect. Recent studies suggest that multiple daily sessions of rTMS can accelerate response without reducing therapeutic efficacy. However, it is unresolved whether therapeutic effects track cumulative number of pulses, or cumulative number of sessions. This open-label study reviewed clinical outcomes over a 20-30 session course of high-frequency bilateral dorsomedial prefrontal cortex (DMPFC)-rTMS among patients receiving 6000 pulses/day delivered either in twice-daily sessions 80 min apart (at 20 Hz) or single, longer, once-daily sessions (at 10 Hz). A retrospective chart review identified 130 MDD patients who underwent 20-30 daily sessions of bilateral DMPFC-rTMS (Once-daily, n = 65; Twice-daily, n = 65) at a single Canadian clinic. Mixed-effects modeling revealed significantly faster improvement (group-by-time interaction) for twice-daily versus once-daily DMPFC-rTMS. Across both groups, the pace of improvement showed a consistent relationship with number of cumulative sessions, but not with cumulative number of pulses. Although the twice-daily group completed treatment in half as many days, final clinical outcomes did not differ significantly between groups on dichotomous measures (response/remission rates: once-daily, 35.4%/33.8%; twice-daily, 41.5%/35.4%), or continuous measures, or on overall response distribution. Twice-daily rTMS appears feasible, tolerable, and capable of achieving comparable results to once-daily rTMS, while also reducing course length approximately twofold. Therapeutic gains tracked the cumulative number of sessions, not pulses. Future randomized studies comparing once-daily to multiple-daily rTMS sessions, while controlling for number of pulses, may be warranted. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

rTMS in fibromyalgia: a randomized trial evaluating QoL and its brain metabolic substrate.

PubMed

Boyer, Laurent; Dousset, Alix; Roussel, Philippe; Dossetto, Nathalie; Cammilleri, Serge; Piano, Virginie; Khalfa, Stéphanie; Mundler, Olivier; Donnet, Anne; Guedj, Eric

2014-04-08

This double-blind, randomized, placebo-controlled study investigated the impact of repetitive transcranial magnetic stimulation (rTMS) on quality of life (QoL) of patients with fibromyalgia, and its possible brain metabolic substrate. Thirty-eight patients were randomly assigned to receive high-frequency rTMS (n = 19) or sham stimulation (n = 19), applied to left primary motor cortex in 14 sessions over 10 weeks. Primary clinical outcomes were QoL changes at the end of week 11, measured using the Fibromyalgia Impact Questionnaire (FIQ). Secondary clinical outcomes were mental and physical QoL component measured using the 36-Item Short Form Health Survey (SF-36), but also pain, mood, and anxiety. Resting-state [(18)F]-fluorodeoxyglucose-PET metabolism was assessed at baseline, week 2, and week 11. Whole-brain voxel-based analysis was performed to study between-group metabolic changes over time. At week 11, patients of the active rTMS group had greater QoL improvement in the FIQ (p = 0.032) and in the mental component of the SF-36 (p = 0.019) than the sham stimulation group. No significant impact was found for other clinical outcomes. Compared with the sham stimulation group, patients of the active rTMS group presented an increase in right medial temporal metabolism between baseline and week 11 (p < 0.001), which was correlated with FIQ and mental component SF-36 concomitant changes (r = -0.38, p = 0.043; r = 0.51, p = 0.009, respectively). QoL improvement involved mainly affective, emotional, and social dimensions. Our study shows that rTMS improves QoL of patients with fibromyalgia. This improvement is associated with a concomitant increase in right limbic metabolism, arguing for a neural substrate to the impact of rTMS on emotional dimensions involved in QoL. This study provides Class II evidence that rTMS compared with sham rTMS improves QoL in patients with fibromyalgia.

Event-related repetitive TMS reveals distinct, critical roles for right OFA and bilateral posterior STS in judging the sex and trustworthiness of faces.

PubMed

Dzhelyova, Milena P; Ellison, Amanda; Atkinson, Anthony P

2011-10-01

Judging the sex of faces relies on cues related to facial morphology and spatial relations between features, whereas judging the trustworthiness of faces relies on both structural and expressive cues that signal affective valence. The right occipital face area (OFA) processes structural cues and has been associated with sex judgments, whereas the posterior STS processes changeable facial cues related to muscle movements and is activated when observers judge trustworthiness. It is commonly supposed that the STS receives inputs from the OFA, yet it is unknown whether these regions have functionally dissociable, critical roles in sex and trustworthiness judgments. We addressed this issue using event-related, fMRI-guided repetitive transcranial magnetic stimulation (rTMS). Twelve healthy volunteers judged the sex of individually presented faces and, in a separate session, whether those same faces were trustworthy or not. Relative to sham stimulation, RTs were significantly longer for sex judgments when rTMS was delivered over the right OFA but not the right or left STS, and for trustworthiness judgments on male but not female faces when rTMS was delivered over the right STS or left STS but not the right OFA. Nonetheless, an analysis of the RT distributions revealed a possible critical role also for the right OFA in trustworthiness judgments, limited to faces with longer RTs, perhaps reflecting the later, ancillary use of structural cues related to the sex of the face. On the whole, our findings provide evidence that evaluations of the trustworthiness and sex of faces rely on functionally dissociable cortical regions.

Coefficient of Friction of Human Corneal Tissue.

PubMed

Wilson, Tawnya; Aeschlimann, Rudolf; Tosatti, Samuele; Toubouti, Youssef; Kakkassery, Joseph; Osborn Lorenz, Katherine

2015-09-01

A novel property evaluation methodology was used to determine the elusive value for the human corneal coefficient of friction (CoF). Using a microtribometer on 28 fresh human donor corneas with intact epithelia, the CoF was determined in 4 test solutions (≥5 corneas/solution): tear-mimicking solution (TMS) in borate-buffered saline (TMS-PS), TMS in phosphate-buffered saline (TMS-PBS), TMS with HEPES-buffered saline (TMS-HEPES), and tear-like fluid in PBS (TLF-PBS). Mean (SD) CoF values ranged from 0.006 to 0.015 and were 0.013 (0.010) in TMS-PS, 0.006 (0.003) in TMS-PBS, 0.014 (0.005) in TMS-HEPES, and 0.015 (0.009) in TLF-PBS. Statistically significant differences were shown for TMS-PBS versus TLF (P = 0.0424) and TMS-PBS versus TMS-HEPES (P = 0.0179), but not for TMS-PBS versus TMS-PS (P = 0.2389). Successful measurement of the fresh human corneal tissue CoF was demonstrated, with values differing in the evaluated buffer solutions, within this limited sample size.

Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder: a navigated transcranial magnetic stimulation (TMS) study.

PubMed

Rogić Vidaković, Maja; Jerković, Ana; Jurić, Tomislav; Vujović, Igor; Šoda, Joško; Erceg, Nikola; Bubić, Andreja; Zmajević Schönwald, Marina; Lioumis, Pantelis; Gabelica, Dragan; Đogaš, Zoran

2016-11-01

Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca's area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 ± 2.07 ms and CoMEP amplitude was 294.47 ± 208.87 µV, and in stuttering subjects CoMEP latency was 12.13 ± 0.75 ms and 504.64 ± 487.93 µV CoMEP amplitude. The latency of LLR in control subjects was 52.8 ± 8.6 ms and 54.95 ± 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.

Repetitive transcranial magnetic stimulation of the right parietal cortex for comorbid generalized anxiety disorder and insomnia: A randomized, double-blind, sham-controlled pilot study.

PubMed

Huang, Zhaoyang; Li, Yue; Bianchi, Matt T; Zhan, Shuqin; Jiang, Fengying; Li, Ning; Ding, Yan; Hou, Yue; Wang, Li; Ouyang, Quping; Wang, Yuping

2018-05-29

Repetitive transcranial magnetic stimulation (rTMS) has been considered to be a promising technique for the treatment of neuropsychiatric disorders. However, little is known about the effectiveness of rTMS in the treatment of generalized anxiety disorder (GAD). Moreover, treatment data on comorbid GAD and insomnia remain lacking. The aim of this study was to examine the therapeutic effects of 1 Hz rTMS applied over the right parietal lobe on both anxiety and insomnia symptoms in patients with comorbid GAD and insomnia. 36 patients were randomized to either sham or active rTMS group (n = 18 each group). The rTMS was administered over the right posterior parietal cortex (P4 electrode site) at a frequency of 1 Hz and an intensity of 90% of the resting motor threshold. Ten days of 1 Hz rTMS to the right parietal lobe significantly improved both anxiety and insomnia symptoms in the active group. Although the anxiety severity was not significantly correlated with insomnia severity at baseline, the improvement in the Hamilton Rating Scale for Anxiety (HRSA) scores were positively correlated with improvement in the Pittsburgh Sleep Quality Index (PSQI) scores. The present study is the first randomized sham-controlled study to assess the effectiveness of low frequency rTMS on the right parietal lobe in patients with comorbid GAD and insomnia. Our results suggested that 1 Hz low frequency rTMS administered over the parietal cortex is effective for both anxiety and insomnia symptoms in patients with comorbid GAD and insomnia. Copyright © 2018 Elsevier Inc. All rights reserved.

Effectiveness of theta-burst repetitive transcranial magnetic stimulation for treating chronic tinnitus.

PubMed

Chung, Hsiung-Kwang; Tsai, Chon-Haw; Lin, Yu-Chin; Chen, Jin-Ming; Tsou, Yung-An; Wang, Chin-Yuan; Lin, Chia-Der; Jeng, Fuh-Cherng; Chung, Jing-Gung; Tsai, Ming-Hsui

2012-01-01

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive method for altering cortical excitability, is becoming a therapeutic strategy in auditory research institutions worldwide. Application of inhibiting rTMS on these overactive cortical regions can result in effective tinnitus suppression. The aim of this study is to investigate the efficacy of theta-burst rTMS in patients with chronic tinnitus. Parallel randomized control study. Tertiary referral center. We enrolled 2 female and 20 male patients in this study. The evaluative tools included tinnitus frequency- and loudness-matching, tinnitus questionnaires (TQ), and the Tinnitus Handicap Inventory (THI). The orthogonal projection of the auditory cortex on the scalp was focalized. A figure-eight coil was placed on the surface of the skull over the targeted region with the intensity setting at 80% of the resting motor threshold. We delivered 900 pulses of theta-burst rTMS daily for 10 business days. Nine of twelve patients (75%) in the active-stimulation group reported tinnitus suppression following treatment with rTMS. The treatment led to reductions of 8.58 and 8.33 in the mean TQ global and THI scores, respectively. Tinnitus loudness also decreased significantly after delivering rTMS. Descriptive analysis of the TQs revealed that patients experienced significant improvements in emotional distress levels and somatic symptoms. Our preliminary results demonstrate that theta-burst rTMS treatments offer a method of modulating tinnitus. Patients could benefit from emotional improvements, even more than auditory perceptive relief. Further studies are needed to establish a standard protocol and to clarify nervous propagation along the auditory and psychological projection following treatment with rTMS. Copyright © 2011 S. Karger AG, Basel.

From pulses to pain relief: an update on the mechanisms of rTMS-induced analgesic effects.

PubMed

Moisset, X; de Andrade, D C; Bouhassira, D

2016-05-01

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action. Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques. Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections. rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action. © 2015 European Pain Federation - EFIC®

Effective elimination of liver cancer stem-like cells by CD90 antibody targeted thermosensitive magnetoliposomes

PubMed Central

Yang, Rui; An, Li Y.; Miao, Qin F.; Li, Feng M.; Han, Yong; Wang, Hui X.; Liu, Dang P.; Chen, Rong; Tang, Sha Q.

2016-01-01

Aim To investigate the use of thermosensitive magnetoliposomes (TMs) loaded with magnetic iron oxide (Fe3O4) and the anti-cancer stem cell marker CD90 (CD90@TMs) to target and kill CD90+ liver cancer stem cells (LCSCs). Methods The hepatocellular carcinoma cell line Huh7 was used to separate CD90+ LCSCs by magnetic-activated cell sorting. CD90@TMs was characterized and their ability to target CD90+ LCSCs was determined. Experiments were used to investigate whether CD90@TMs combined with magnetic hyperthermia could effectively eliminate CD90+ LCSCs. Results The present study demonstrated that CD90+ LCSCs with stem cells properties were successfully isolated. We also successfully prepared CD90@TMs that was almost spherical and uniform with an average diameter of 130±4.6 nm and determined that magnetic iron oxide could be incorporated and retained a superparamagnetic response. CD90@TMs showed good targeting and increased inhibition of CD90+ LCSCs in vitro and in vivo compared to TMs. Conclusion CD90@TMs can be used for controlled and targeted delivery of anticancer drugs, which may offer a promising alternative for HCC therapy. PMID:27145285

Antidepressant effectiveness of deep Transcranial Magnetic Stimulation (dTMS) in patients with Major Depressive Disorder (MDD) with or without Alcohol Use Disorders (AUDs): a 6-month, open label, follow-up study.

PubMed

Rapinesi, Chiara; Curto, Martina; Kotzalidis, Georgios D; Del Casale, Antonio; Serata, Daniele; Ferri, Vittoria Rachele; Di Pietro, Simone; Scatena, Paola; Bersani, Francesco Saverio; Raccah, Ruggero Nessim; Digiacomantonio, Vittorio; Ferracuti, Stefano; Bersani, Giuseppe; Zangen, Abraham; Angeletti, Gloria; Girardi, Paolo

2015-03-15

Co-occurrence of Major Depressive (MDD) and Alcohol Use Disorders (AUDs) is frequent, causing more burden than each disorder separately. Since the dorsolateral prefrontal cortex (DLPFC) is critically involved in both mood and reward and dysfunctional in both conditions, we aimed to evaluate the effects of dTMS stimulation of bilateral DLPFC with left prevalence in patients with MDD with or without concomitant AUD. Twelve MDD patients and 11 with concomitant MDD and AUD (MDD+AUD) received 20 dTMS sessions. Clinical status was assessed through the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions severity scale (CGIs), craving through the Obsessive Compulsive Drinking Scale (OCDS) in MDD+AUD, and functioning with the Global Assessment of Functioning (GAF). There were no significant differences between the two groups in sociodemographic (age, sex, years of education and duration of illness) and baseline clinical characteristics, including scores on assessment scales. Per cent drops on HDRS and CGIs scores at the end of the sessions were respectively 62.6% and 78.2% for MDD+AUD, and 55.2% and 67.1% for MDD (p<0.001). HDRS, CGIs and GAF scores remained significantly improved after the 6-month follow-up. HDRS scores dropped significantly earlier in MDD+AUD than in MDD LIMITATIONS: The small sample size and factors inherent to site and background treatment may have affected results. High frequency bilateral DLPFC dTMS with left preference was well tolerated and effective in patients with MDD, with or without AUD. The antidepressant effect of dTMS is not affected by alcohol abuse in patients with depressive episodes. The potential use of dTMS for mood modulation as an adjunct to treatment in patients with a depressive episode, with or without alcohol abuse, deserves further investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

Evoking visual neglect-like deficits in healthy volunteers - an investigation by repetitive navigated transcranial magnetic stimulation.

PubMed

Giglhuber, Katrin; Maurer, Stefanie; Zimmer, Claus; Meyer, Bernhard; Krieg, Sandro M

2017-02-01

In clinical practice, repetitive navigated transcranial magnetic stimulation (rTMS) is of particular interest for non-invasive mapping of cortical language areas. Yet, rTMS studies try to detect further cortical functions. Damage to the underlying network of visuospatial attention function can result in visual neglect-a severe neurological deficit and influencing factor for a significantly reduced functional outcome. This investigation aims to evaluate the use of rTMS for evoking visual neglect in healthy volunteers and the potential of specifically locating cortical areas that can be assigned for the function of visuospatial attention. Ten healthy, right-handed subjects underwent rTMS visual neglect mapping. Repetitive trains of 5 Hz and 10 pulses were applied to 52 pre-defined cortical spots on each hemisphere; each cortical spot was stimulated 10 times. Visuospatial attention was tested time-locked to rTMS pulses by a landmark task. Task pictures were displayed tachistoscopically for 50 ms. The subjects' performance was analyzed by video, and errors were referenced to cortical spots. We observed visual neglect-like deficits during the stimulation of both hemispheres. Errors were categorized into leftward, rightward, and no response errors. Rightward errors occurred significantly more often during stimulation of the right hemisphere than during stimulation of the left hemisphere (mean rightward error rate (ER) 1.6 ± 1.3 % vs. 1.0 ± 1.0 %, p = 0.0141). Within the left hemisphere, we observed predominantly leftward errors rather than rightward errors (mean leftward ER 2.0 ± 1.3 % vs. rightward ER 1.0 ± 1.0 %; p = 0.0005). Visual neglect can be elicited non-invasively by rTMS, and cortical areas eloquent for visuospatial attention can be detected. Yet, the correlation of this approach with clinical findings has to be shown in upcoming steps.

Convergence of flexor reflex and corticospinal inputs on tibialis anterior network in humans.

PubMed

Mackey, Ann S; Uttaro, Denise; McDonough, Maureen P; Krivis, Lisa I; Knikou, Maria

2016-01-01

Integration between descending and ascending inputs at supraspinal and spinal levels is a key characteristic of neural control of movement. In this study, we characterized convergence of the flexor reflex and corticospinal inputs on the tibialis anterior (TA) network in healthy human subjects. Specifically, we characterized the modulation profiles of the spinal TA flexor reflex following subthreshold and suprathreshold transcranial magnetic stimulation (TMS). We also characterized the modulation profiles of the TA motor evoked potentials (MEPs) following medial arch foot stimulation at sensory and above reflex threshold. TA flexor reflexes were evoked following stimulation of the medial arch of the foot with a 30 ms pulse train at innocuous intensities. TA MEPs were evoked following TMS of the leg motor cortex area. TMS at 0.7 and at 1.2 MEP resting threshold increased the TA flexor reflex when TMS was delivered 40-100 ms after foot stimulation, and decreased the TA flexor reflex when TMS was delivered 25-110 ms before foot stimulation. Foot stimulation at sensory and above flexor reflex threshold induced a similar time-dependent modulation in resting TA MEPs, that were facilitated when foot stimulation was delivered 40-100 ms before TMS. The flexor reflex and MEPs recorded from the medial hamstring muscle were modulated in a similar manner to that observed for the TA flexor reflex and MEP. Cutaneomuscular afferents from the distal foot can increase the output of the leg motor cortex area. Descending motor volleys that directly or indirectly depolarize flexor motoneurons increase the output of the spinal FRA interneuronal network. The parallel facilitation of flexor MEPs and flexor reflexes is likely cortical in origin. Afferent mediated facilitation of corticospinal excitability can be utilized to strengthen motor cortex output in neurological disorders. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Towards assessing corticospinal excitability bilaterally: Validation of a double-coil TMS method.

PubMed

Grandjean, Julien; Derosiere, Gerard; Vassiliadis, Pierre; Quemener, Louise; Wilde, Ysaline de; Duque, Julie

2018-01-01

For several decades, Transcranial magnetic stimulation (TMS) has been used to monitor corticospinal excitability (CSE) changes in various contexts. Habitually, single-coil TMS is applied over one primary motor cortex (M1), eliciting motor-evoked potentials (MEPs) in a contralateral limb muscle, usually a hand effector. However, in many situations, it would be useful to obtain MEPs in both hands simultaneously, to track CSE bilaterally. Such an approach requires stimulating both M1 concurrently while avoiding interference between the two descending stimuli. We examined MEPs obtained at rest using a double-coil TMS approach where the two M1 are stimulated with a 1ms inter-pulse interval (double-coil 1ms ). MEPs were acquired using double-coil 1ms (MEP double ) or single-coil (MEP single ) TMS, at five different intensities of stimulation (100, 115, 130, 145 or 160% of the resting motor threshold, rMT). Given the 1ms inter-pulse interval in double-coil 1ms trials, MEP double were either evoked by a 1st (MEP double-1 ) or a 2nd (MEP double-2 ) TMS pulse. All MEP TYPE (MEP TYPE =MEP single , MEP double-1 and MEP double-2 ) were equivalent, regardless of the hand within which they were elicited, the intensity of stimulation or the pulse order. This method allows one to observe state-related CSE changes for the two hands simultaneously on a trial-by-trial basis. These results infer the absence of any neural interactions between the two cortico-spinal volleys with double-coil 1ms TMS. Hence, this technique can be reliably used to assess CSE bilaterally, opening new research perspectives for scientists interested in physiological markers of activity in the motor output system. Copyright © 2017 Elsevier B.V. All rights reserved.

A Double-Coil TMS Method to Assess Corticospinal Excitability Changes at a Near-Simultaneous Time in the Two Hands during Movement Preparation

PubMed Central

Wilhelm, Emmanuelle; Quoilin, Caroline; Petitjean, Charlotte; Duque, Julie

2016-01-01

Background: Many previous transcranial magnetic stimulation (TMS) studies have investigated corticospinal excitability changes occurring when choosing which hand to use for an action, one of the most frequent decision people make in daily life. So far, these studies have applied single-pulse TMS eliciting motor-evoked potential (MEP) in one hand when this hand is either selected or non-selected. Using such method, hand choices were shown to entail the operation of two inhibitory mechanisms, suppressing MEPs in the targeted hand either when it is non-selected (competition resolution, CR) or selected (impulse control, IC). However, an important limitation of this “Single-Coil” method is that MEPs are elicited in selected and non-selected conditions during separate trials and thus those two settings may not be completely comparable. Moreover, a more important problem is that MEPs are computed in relation to the movement of different hands. The goal of the present study was to test a “Double-Coil” method to evaluate IC and CR preceding the same hand responses by applying Double-Coil TMS over the two primary motor cortices (M1) at a near-simultaneous time (1 ms inter-pulse interval). Methods: MEPs were obtained in the left (MEPLEFT) and right (MEPRIGHT) hands while subjects chose between left and right hand key-presses in blocks using a Single-Coil or a Double-Coil method; in the latter blocks, TMS was either applied over left M1 first (TMSLRM1 group, n = 12) or right M1 first (TMSRLM1 group, n = 12). Results: MEPLEFT were suppressed preceding both left (IC) and right (CR) hand responses whereas MEPRIGHT were only suppressed preceding left (CR) but not right (IC) hand responses. This result was observed regardless of whether Single-Coil or Double-Coil TMS was applied in the two subject groups. However, in the TMSLRM1 group, the MEP suppression was attenuated in Double-Coil compared to Single-Coil blocks for both IC and CR, when probed with MEPLEFT (elicited by the second pulse). Conclusions: Although Double-Coil TMS may be a reliable method to assess bilateral motor excitability provided that a RM1-LM1 pulse order is used, further experiments are required to understand the reduced MEPLEFT changes in Double-Coil blocks when the LM1-RM1 pulse order was used. PMID:27014020

Chemical constituents and toxicological studies of leaves from Mimosa caesalpiniifolia Benth., a Brazilian honey plant

PubMed Central

Monção, Nayana Bruna Nery; Costa, Luciana Muratori; Arcanjo, Daniel Dias Rufino; Araújo, Bruno Quirino; Lustosa, Maria do Carmo Gomes; Rodrigues, Klinger Antônio da França; Carvalho, Fernando Aécio de Amorim; Costa, Amilton Paulo Raposo; Lopes Citó, Antônia Maria das Graças

2014-01-01

Background: Mimosa caesalpiniifolia Benth. (Leguminosae) is widely found in the Brazilian Northeast region and markedly contributes to production of pollen and honey, being considered an important honey plant in this region. Objective: To investigate the chemical composition of the ethanol extract of leaves from M. caesalpiniifolia by GC-MS after derivatization (silylation), as well as to evaluate the in vitro and in vivo toxicological effects and androgenic activity in rats. Materials and Methods: The ethanol extract of leaves from Mimosa caesalpiniifolia was submitted to derivatization by silylation and analyzed by gas chromatography-mass spectrometry (GC-MS) to identification of chemical constituents. In vitro toxicological evaluation was performed by MTT assay in murine macrophages and by Artemia salina lethality assay, and the in vivo acute oral toxicity and androgenic evaluation in rats. Results: Totally, 32 components were detected: Phytol-TMS (11.66%), lactic acid-2TMS (9.16%), α-tocopherol-TMS (7.34%) and β-sitosterol-TMS (6.80%) were the major constituents. At the concentrations analyzed, the ethanol extract showed low cytotoxicity against brine shrimp (Artemia salina) and murine macrophages. In addition, the extract did not exhibit any toxicological effect or androgenic activity in rats. Conclusions: The derivatization by silylation allowed a rapid identification of chemical compounds from the M. caesalpiniifolia leaves extract. Besides, this species presents a good safety profile as observed in toxicological studies, and possess a great potential in the production of herbal medicines or as for food consumption. PMID:25298660

Overt Naming fMRI Pre- and Post- TMS: Two Nonfluent Aphasia Patients, with and without Improved Naming Post- TMS

PubMed Central

Martin, Paula I; Naeser, Margaret A.; Ho, Michael; Doron, Karl W.; Kurland, Jacquie; Kaplan, Jerome; Wang, Yunyan; Nicholas, Marjorie; Baker, Errol H.; Alonso, Miguel; Fregni, Felipe; Pascual-Leone, Alvaro

2009-01-01

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post- a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received ten, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a ‘good responder’ with improved naming and phrase length; P2 was a ‘poor responder’ without improved naming. Pre- TMS (10 yr. poststroke), P1 had significant activation in R and L sensorimotor cortex, R IFG, and in both L and R SMA during overt naming fMRI (28% pictures named. At 3 mo. post- TMS (42% named), P1 showed continued activation in R and L sensorimotor cortex, R IFG, and in R and L SMA. At 16 mo. post- TMS (58% named), he also showed significant activation in R and L sensorimotor cortex mouth and R IFG. He now showed a significant increase in activation in the L SMA compared to pre- TMS and at 3 mo. post- TMS (p<.02; p<.05, respectively). At 16 mo. there was also greater activation in L than R SMA (p<.08). At 46 mo. post- TMS (42% named), this new LH pattern of activation continued. He improved on the Boston Naming Test from 11 pictures named pre- TMS, to scores ranging from 14-18 pictures, post- TMS (2 mo. to 43 mo. post- TMS). His longest phrase length (Cookie Theft picture) improved from 3 words pre- TMS, to 5-6 words post- TMS. Pre- TMS (1.5 yr. poststroke), P2 had significant activation in R IFG (3% pictures named). At 3 and 6 mo. post- TMS, there was no longer significant activation in R IFG, but significant activation was present in R sensorimotor cortex. On all three fMRI scans, P2 had significant activation in both the L and R SMA. There was no new, lasting perilesional LH activation across sessions for this patient. Over time, there was little or no change in his activation. His naming remained only at 1-2 pictures during all three fMRI scans. His BNT score and longest phrase length remained at 1 word, post- TMS. Lesion site may play a role in each patient’s fMRI activation pattern and response to TMS treatment. P2, the poor responder, had an atypical frontal lesion in the L motor and premotor cortex that extended high, near brain vertex, with deep white matter lesion near L SMA. P2 also had frontal lesion in the posterior middle frontal gyrus, an area important for naming (Duffau et al., 2003); P1 did not. Additionally, P2 had lesion inferior and posterior to Wernicke’s area, in parts of BA 21 and 37, whereas P1 did not. The fMRI data of our patient who had good response following TMS support the notion that restoration of the LH language network is linked in part, to better recovery of naming and phrase length in nonfluent aphasia. PMID:19695692

Overt naming fMRI pre- and post-TMS: Two nonfluent aphasia patients, with and without improved naming post-TMS.

PubMed

Martin, Paula I; Naeser, Margaret A; Ho, Michael; Doron, Karl W; Kurland, Jacquie; Kaplan, Jerome; Wang, Yunyan; Nicholas, Marjorie; Baker, Errol H; Alonso, Miguel; Fregni, Felipe; Pascual-Leone, Alvaro

2009-10-01

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post-a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received 10, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a 'good responder' with improved naming and phrase length; P2 was a 'poor responder' without improved naming. Pre-TMS (10 years poststroke), P1 had significant activation in R and L sensorimotor cortex, R IFG, and in both L and R SMA during overt naming fMRI (28% pictures named). At 3 mo. post-TMS (42% named), P1 showed continued activation in R and L sensorimotor cortex, R IFG, and in R and L SMA. At 16 mo. post-TMS (58% named), he also showed significant activation in R and L sensorimotor cortex mouth and R IFG. He now showed a significant increase in activation in the L SMA compared to pre-TMS and at 3 mo. post-TMS (p < .02; p < .05, respectively). At 16 mo. there was also greater activation in L than R SMA (p < .08). At 46 mo. post-TMS (42% named), this new LH pattern of activation continued. He improved on the Boston Naming Test from 11 pictures named pre-TMS, to scores ranging from 14 to 18 pictures, post-TMS (2-43 mo. post-TMS). His longest phrase length (Cookie Theft picture) improved from three words pre-TMS, to 5-6 words post-TMS. Pre-TMS (1.5 years poststroke), P2 had significant activation in R IFG (3% pictures named). At 3 and 6 mo. post-TMS, there was no longer significant activation in R IFG, but significant activation was present in R sensorimotor cortex. On all three fMRI scans, P2 had significant activation in both the L and R SMA. There was no new, lasting perilesional LH activation across sessions for this patient. Over time, there was little or no change in his activation. His naming remained only at 1-2 pictures during all three fMRI scans. His BNT score and longest phrase length remained at one word, post-TMS. Lesion site may play a role in each patient's fMRI activation pattern and response to TMS treatment. P2, the poor responder, had an atypical frontal lesion in the L motor and premotor cortex that extended high, near brain vertex, with deep white matter lesion near L SMA. P2 also had frontal lesion in the posterior middle frontal gyrus, an area important for naming (Duffau et al., 2003); P1 did not. Additionally, P2 had lesion inferior and posterior to Wernicke's area, in parts of BA 21 and 37, whereas P1 did not. The fMRI data of our patient who had good response following TMS support the notion that restoration of the LH language network is linked in part, to better recovery of naming and phrase length in nonfluent aphasia.

Hemispheric differences in the voluntary control of spatial attention: direct evidence for a right-hemispheric dominance within frontal cortex.

PubMed

Duecker, Felix; Formisano, Elia; Sack, Alexander T

2013-08-01

Lesion studies in neglect patients have inspired two competing models of spatial attention control, namely, Heilman's "hemispatial" theory and Kinsbourne's "opponent processor" model. Both assume a functional asymmetry between the two hemispheres but propose very different mechanisms. Neuroimaging studies have identified a bilateral dorsal frontoparietal network underlying voluntary shifts of spatial attention. However, lateralization of attentional processes within this network has not been consistently reported. In the current study, we aimed to provide direct evidence concerning the functional asymmetry of the right and left FEF during voluntary shifts of spatial attention. To this end, we applied fMRI-guided neuronavigation to disrupt individual FEF activation foci with a longer-lasting inhibitory patterned TMS protocol followed by a spatial cueing task. Our results indicate that right FEF stimulation impaired the ability of shifting spatial attention toward both hemifields, whereas the effects of left FEF stimulation were limited to the contralateral hemifield. These results provide strong direct evidence for right-hemispheric dominance in spatial attention within frontal cortex supporting Heilman's "hemispatial" theory. This complements previous TMS studies that generally conform to Kinsbourne's "opponent processor" model after disruption of parietal cortex, and we therefore propose that both theories are not mutually exclusive.

Improved naming after TMS treatments in a chronic, global aphasia patient — case report

PubMed Central

NAESER, MARGARET A.; MARTIN, PAULA I; NICHOLAS, MARJORIE; BAKER, ERROL H.; SEEKINS, HEIDI; HELM-ESTABROOKS, NANCY; CAYER-MEADE, CAROL; KOBAYASHI, MASAHITO; THEORET, HUGO; FREGNI, FELIPE; TORMOS, JOSE MARIA; KURLAND, JACQUIE; DORON, KARL W.; PASCUAL-LEONE, ALVARO

2005-01-01

We report improved ability to name pictures at 2 and 8 months after repetitive transcranial magnetic stimulation (rTMS) treatments to the pars triangularis portion of right Broca’s homologue in a 57 year-old woman with severe nonfluent/global aphasia (6.5 years post left basal ganglia bleed, subcortical lesion). TMS was applied at 1 Hz, 20 minutes a day, 10 days, over a two-week period. She received no speech therapy during the study. One year after her TMS treatments, she entered speech therapy with continued improvement. TMS may have modulated activity in the remaining left and right hemisphere neural network for naming. PMID:16006338

Short-term modulation of regional excitability and blood flow in human motor cortex following rapid-rate transcranial magnetic stimulation.

PubMed

Takano, Beatrice; Drzezga, Alexander; Peller, Martin; Sax, Iris; Schwaiger, Markus; Lee, Lucy; Siebner, Hartwig Roman

2004-11-01

Repetitive transcranial magnetic stimulation (rTMS) of the human primary motor cortex (M1) provides a means of inducing lasting changes in cortical excitability and synaptic activity. Here we combined rTMS with positron emission tomography of regional cerebral blood flow (rCBF) to examine how an rTMS-induced change in intracortical excitability of inhibitory circuits affects regional synaptic activity. In a first set of experiments, we gave 150 biphasic pulses of 5 Hz rTMS at 90% of active motor threshold to left M1 and used single- and paired-pulse TMS to assess the conditioning effects of rTMS on motor cortical excitability at rest. rTMS conditioning led to a selective decrease in short-latency intracortical inhibition (SICI) without affecting short-latency intracortical facilitation or corticospinal excitability. The decrease in SICI lasted for approximately 8 min. In a second experiment, we used the same rTMS protocol and measured changes in regional synaptic activity (as indexed by rCBF) during and for up to 14 min after the end of rTMS. Subthreshold 5 Hz rTMS induced a region-specific increase in resting rCBF in the stimulated M1 lasting approximately 8 min. These results suggest that in the stimulated M1, temporary attenuation of SICI is paralleled by an increase in synaptic activity, consistent with reduced efficacy of intracortical GABA(A)-ergic synapses. The present findings demonstrate that short trains of low-intensity 5 Hz rTMS can be used to induce a transient change in function within a distinct cortical area. This opens up new possibilities for studying acute reorganization at the systems level in the intact human brain.

Interaction of paired cortical and peripheral nerve stimulation on human motor neurons.

PubMed

Poon, David E; Roy, Francois D; Gorassini, Monica A; Stein, Richard B

2008-06-01

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10-25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50-60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.

EIMS Fragmentation Pathways and MRM Quantification of 7α/β-Hydroxy-Dehydroabietic Acid TMS Derivatives

NASA Astrophysics Data System (ADS)

Rontani, Jean-François; Aubert, Claude; Belt, Simon T.

2015-09-01

EI mass fragmentation pathways of TMS derivatives οf 7α/β-hydroxy-dehydroabietic acids resulting from NaBH4-reduction of oxidation products of dehydroabietic acid (a component of conifers) were investigated and deduced by a combination of (1) low energy CID-GC-MS/MS, (2) deuterium labeling, (3) different derivatization methods, and (4) GC-QTOF accurate mass measurements. Having identified the main fragmentation pathways, the TMS-derivatized 7α/β-hydroxy-dehydroabietic acids could be quantified in multiple reaction monitoring (MRM) mode in sea ice and sediment samples collected from the Arctic. These newly characterized transformation products of dehydroabietic acid constitute potential tracers of biotic and abiotic degradation of terrestrial higher plants in the environment.

Transcranial magnetic stimulation (TMS) in Attention Deficit Hyperactivity Disorder (ADHD).

PubMed

Zaman, Rashid

2015-09-01

Attention Deficit Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder, which affects children as well as adults and leads to significant impairment in educational, social and occupational functioning and has associated personal and societal costs. Whilst there are effective medications (mostly stimulants) as well as some psychobehavioural treatments that help alleviate symptoms of ADHD, there is still need to improve our understanding of its neurobiology as well as explore other treatment options. Transcranial Magnetic Stimulation (TMS) and repetitive transcranial magnetic stimulation (rTMS) are safe and non-invasive investigative and therapeutic tools respectively. In this short article, I will explore their potential for improving our understanding of the neurobiology of ADHD as well consider its as a possible treatment option.

Changes in canine cerebral perfusion after accelerated high frequency repetitive transcranial magnetic stimulation (HF-rTMS): A proof of concept study.

PubMed

Dockx, R; Baeken, C; Duprat, R; De Vos, F; Saunders, J H; Polis, I; Audenaert, K; Peremans, K

2018-04-01

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for several neuropsychiatric disorders in human beings, but the neurobiological effects of rTMS in dogs have not been investigated to date. A proof of concept study was designed to evaluate the effect of rTMS on cerebral perfusion, measured with single photon emission computed tomography (SPECT), in dogs. An accelerated high frequency (aHF)-rTMS (20Hz) protocol was applied to the canine left frontal cortex. To accurately target this area, eight dogs underwent a 3 Tesla magnetic resonance imaging (MRI) scan before stimulation. The left frontal cortex was subjected to five consecutive aHF-rTMS sessions with a figure-of-eight coil designed for human beings at an intensity of 110% of the motor threshold. The dogs underwent 99m Tc-d,1 hexamethylpropylene amine oxime (HMPAO) SPECT scans 1 week prior to and 1day after the stimulations. Perfusion indices (PIs) were determined semi-quantitatively; aHF-rTMS resulted in significantly increased PIs in the left frontal cortex and the subcortical region, whereas no significant differences were noted for the other regions. Behaviour was not influenced by the stimulation sessions. As has been observed in human beings, aHF-rTMS applied to the left frontal cortex alters regional cerebral perfusion in dogs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Does an intraneural interface short-term implant for robotic hand control modulate sensorimotor cortical integration? An EEG-TMS co-registration study on a human amputee.

PubMed

Ferreri, F; Ponzo, D; Vollero, L; Guerra, A; Di Pino, G; Petrichella, S; Benvenuto, A; Tombini, M; Rossini, L; Denaro, L; Micera, S; Iannello, G; Guglielmelli, E; Denaro, V; Rossini, P M

2014-01-01

Following limb amputation, central and peripheral nervous system relays partially maintain their functions and can be exploited for interfacing prostheses. The aim of this study is to investigate, for the first time by means of an EEG-TMS co-registration study, whether and how direct bidirectional connection between brain and hand prosthesis impacts on sensorimotor cortical topography. Within an experimental protocol for robotic hand control, a 26 years-old, left-hand amputated male was selected to have implanted four intrafascicular electrodes (tf-LIFEs-4) in the median and ulnar nerves of the stump for 4 weeks. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subject's cortico-cortical excitability, connectivity and plasticity were tested via a neuronavigated EEG-TMS experiment. The statistical analysis clearly demonstrated a significant modulation (with t-test p < 0.0001) of EEG activity between 30 and 100 ms post-stimulus for the stimulation of the right hemisphere. When studying individual latencies in that time range, a global amplitude modulation was found in most of the TMS-evoked potentials; particularly, the GEE analysis showed significant differences between T0 and T1 condition at 30 ms (p < 0.0404), 46 ms (p < 0.0001) and 60 ms (p < 0.007) latencies. Finally, also a clear local decrement in N46 amplitude over C4 was evident. No differences between conditions were observed for the stimulation of the left hemisphere. The results of this study confirm the hypothesis that bidirectional neural interface could redirect cortical areas -deprived of their original input/output functions- toward restorative neuroplasticity. This reorganization strongly involves bi-hemispheric networks and intracortical and transcortical modulation of GABAergic inhibition.

Transient alcohol craving suppression by rTMS of dorsal anterior cingulate: an fMRI and LORETA EEG study.

PubMed

De Ridder, Dirk; Vanneste, Sven; Kovacs, Silvia; Sunaert, Stefan; Dom, Geert

2011-05-27

It has recently become clear that alcohol addiction might be related to a brain dysfunction, in which a genetic background and environmental factors shape brain mechanisms involved with alcohol consumption. Craving, a major component determining relapses in alcohol abuse has been linked to abnormal activity in the orbitofrontal cortex, dorsal anterior cingulated cortex (dACC) and amygdala. We report the results of a patient who underwent rTMS targeting the dACC using a double cone coil in an attempt to suppress very severe intractable alcohol craving. Functional imaging studies consisting of fMRI and resting state EEG were performed before rTMS, after successful rTMS and after unsuccessful rTMS with relapse. Craving was associated with EEG beta activity and connectivity between the dACC and PCC in the patient in comparison to a healthy population, which disappeared after successful rTMS. Cue induced worsening of craving pre-rTMS activated the ACC-vmPFC and PCC on fMRI, as well as the nucleus accumbens area, and lateral frontoparietal areas. The nucleus accumbens, ACC-vmPFC and PCC activation disappeared on fMRI following successful rTMS. Relapse was associated with recurrence of ACC and PCC EEG activity, but in gamma band, in comparison to a healthy population. On fMRI nucleus accumbens, ACC and PCC activation returned to the initial activation pattern. A pathophysiological approach is described to suppress alcohol craving temporarily by rTMS directed at the anterior cingulate. Linking functional imaging changes to craving intensity suggests this approach warrants further exploration. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

Scripting for Construction of a Transactive Memory System in Multidisciplinary CSCL Environments

ERIC Educational Resources Information Center

Noroozi, Omid; Biemans, Harm J. A.; Weinberger, Armin; Mulder, Martin; Chizari, Mohammad

2013-01-01

Establishing a Transactive Memory System (TMS) is essential for groups of learners, when they are multidisciplinary and collaborate online. Environments for Computer-Supported Collaborative Learning (CSCL) could be designed to facilitate the TMS. This study investigates how various aspects of a TMS (i.e., specialization, coordination, and trust)…

Consecutive TMS-fMRI reveals remote effects of neural noise to the "occipital face area".

PubMed

Solomon-Harris, Lily M; Rafique, Sara A; Steeves, Jennifer K E

2016-11-01

The human cortical system for face perception comprises a network of connected regions including the middle fusiform gyrus ("fusiform face area" or FFA), the inferior occipital gyrus ("occipital face area" or OFA), and the posterior superior temporal sulcus (pSTS). Here, we sought to investigate how transcranial magnetic stimulation (TMS) to the OFA affects activity within the face processing network. We used offline repetitive TMS to temporarily introduce neural noise in the right OFA in healthy subjects. We then immediately performed functional magnetic resonance imaging (fMRI) to measure changes in blood oxygenation level dependent (BOLD) signal across the face network using an fMR-adaptation (fMR-A) paradigm. We hypothesized that TMS to the right OFA would induce abnormal face identity coding throughout the face processing network in regions to which it has direct or indirect connections. Indeed, BOLD signal for face identity, but not non-face (butterfly) identity, decreased in the right OFA and FFA following TMS to the right OFA compared to both sham TMS and TMS to a control site, the nearby object-related lateral occipital area (LO). Further, TMS to the right OFA decreased face-related activation in the left FFA, without any effect in the left OFA. Our findings indicate that TMS to the right OFA selectively disrupts face coding at both the stimulation site and bilateral FFA. TMS to the right OFA also decreased BOLD signal for different identity stimuli in the right pSTS. Together with mounting evidence from patient studies, we demonstrate connectivity of the OFA within the face network and that its activity modulates face processing in bilateral FFA as well as the right pSTS. Moreover, this study shows that deep regions within the face network can be remotely probed by stimulating structures closer to the cortical surface. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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.

Effects of cerebellar neuromodulation in movement disorders: A systematic review.

PubMed

França, Carina; de Andrade, Daniel Ciampi; Teixeira, Manoel Jacobsen; Galhardoni, Ricardo; Silva, Valquiria; Barbosa, Egberto Reis; Cury, Rubens Gisbert

The cerebellum is involved in the pathophysiology of many movement disorders and its importance in the field of neuromodulation is growing. To review the current evidence for cerebellar modulation in movement disorders and its safety profile. Eligible studies were identified after a systematic literature review of the effects of cerebellar modulation in cerebellar ataxia, Parkinson's disease (PD), essential tremor (ET), dystonia and progressive supranuclear palsy (PSP). Neuromodulation techniques included transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS). The changes in motor scores and the incidence of adverse events after the stimulation were reviewed. Thirty-four studies were included in the systematic review, comprising 431 patients. The evaluation after stimulation ranged from immediately after to 12 months after. Neuromodulation techniques improved cerebellar ataxia due to vascular or degenerative etiologies (TMS, tDCS and DBS), dyskinesias in PD patients (TMS), gross upper limb movement in PD patients (tDCS), tremor in ET (TMS and tDCS), cervical dystonia (TMS and tDCS) and dysarthria in PSP patients (TMS). All the neuromodulation techniques were safe, since only three studies reported the existence of side effects (slight headache after TMS, local skin erythema after tDCS and infectious complication after DBS). Eleven studies did not mention if adverse events occurred. Cerebellar modulation can improve specific symptoms in some movement disorders and is a safe and well-tolerated procedure. Further studies are needed to lay the groundwork for new researches in this promising target. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery.

PubMed

Kubis, Nathalie

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies, have shown various effects on the functional disability score and neurological scales of treated patients and on the duration of the treatment. We review here the patients' characteristics and parameters of stimulation that could predict a good response, as well as safety issues. At last, we review what we have learnt from experimental studies and discuss potential directions to conduct future studies.

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery

PubMed Central

Kubis, Nathalie

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies, have shown various effects on the functional disability score and neurological scales of treated patients and on the duration of the treatment. We review here the patients’ characteristics and parameters of stimulation that could predict a good response, as well as safety issues. At last, we review what we have learnt from experimental studies and discuss potential directions to conduct future studies. PMID:27512367

Motor Cortex Reorganization and Repetitive Transcranial Magnetic Stimulation for Pain-A Methodological Study.

PubMed

Nurmikko, Turo; MacIver, Kathryn; Bresnahan, Rebecca; Hird, Emily; Nelson, Andrew; Sacco, Paul

2016-10-01

Somatotopic reorganization of primary motor cortex (M1) has been described in several neurological conditions associated with chronic pain. We hypothesized that such reorganization impacts on the mechanisms of M1 stimulation induced analgesia and may either compromise the treatment effect of or provide an alternative target site for repetitive transcranial magnetic stimulation (rTMS). The aim of the study was to compare pain relief following rTMS of the standard motor "hotspot" with that of the reorganized area. We used TMS motor mapping in 30 patients to establish the location of the standard motor "hotspot" (site A) and an alternative site located in the reorganized area (site B), both within M1. Where TMS mapping was not possible (N = 8) we determined the location of the two sites using task-related fMRI. We compared the analgesic effect on neuropathic pain of 5 sessions of navigated rTMS applied over (i) site A, (ii) site B, and (iii) occipital fissure (SHAM stimulation site). Total Pain Relief (TOTPAR) was determined as the difference in average weekly pain scores between baseline and following each rTMS cycle, over three weeks. Data from 27 patients was analyzed. rTMS of sites A and B resulted in greater TOTPAR than that of SHAM. No difference was seen between sites A and B. Responders (≥15% pain relief) were seen in both groups, with partial overlap only. Addition of stimulation over site B improved the responder rate by 58% compared with site A. In an open-label extension study of five sessions of rTMS aimed at the optimized target site, 8/11 responders and 1/12 nonresponders reported pain relief. Cortical reorganization may provide a more effective stimulation target for rTMS in some individuals with neuropathic pain. © 2016 International Neuromodulation Society.

Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study.

PubMed

Attal, Nadine; Ayache, Samar S; Ciampi De Andrade, Daniel; Mhalla, Alaa; Baudic, Sophie; Jazat, Frédérique; Ahdab, Rechdi; Neves, Danusa O; Sorel, Marc; Lefaucheur, Jean-Pascal; Bouhassira, Didier

2016-06-01

No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain.

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation.

PubMed

Kumru, Hatice; Albu, Sergiu; Rothwell, John; Leon, Daniel; Flores, Cecilia; Opisso, Eloy; Tormos, Josep Maria; Valls-Sole, Josep

2017-10-01

Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle. Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention. Magnetic-PAS , but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle. Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle. Application of magnetic-PAS might be relevant for motor rehabilitation. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

The role of medial prefrontal cortex in theory of mind: a deep rTMS study.

PubMed

Krause, Laura; Enticott, Peter G; Zangen, Abraham; Fitzgerald, Paul B

2012-03-01

Neuroimaging studies suggest that the medial prefrontal cortex (mPFC) plays a central role in cognitive theory of mind (ToM). This can be assessed more definitively, however, using repetitive transcranial magnetic stimulation (rTMS). Sixteen healthy participants (10 females, 6 males) completed tasks assessing cognitive and affective ToM following low-frequency deep rTMS to bilateral mPFC in active-stimulation and placebo-stimulation sessions. There was no effect of deep rTMS on either cognitive or affective ToM performance. When examining self-reported empathy, however, there was evidence for a double dissociation: deep rTMS disrupted affective ToM performance for those with high self-reported empathy, but improved affective ToM performance for those with low self-reported empathy. mPFC appears to play a role in affective ToM processing, but the present study suggest that stimulation outcomes are dependent on baseline empathic abilities. Copyright © 2011 Elsevier B.V. All rights reserved.

The role of the inferior frontal gyri in cognitive processing of patients with Parkinson's disease: a pilot rTMS study.

PubMed

Srovnalova, Hana; Marecek, Radek; Rektorova, Irena

2011-07-01

We studied whether 1 session of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied sequentially over both the left and right inferior frontal gyri (IFG) would enhance performance in tests evaluating the ability to inhibit habitual responses (Stroop test, ST; Frontal Assessment Battery, FAB) in patients with Parkinson's disease (PD). Ten nondemented PD patients (6 men, 4 women; age, 66 ± 6 years; disease duration, 5.4 ± 2.45 years) entered the randomized, sham stimulation-controlled study with a crossover design. The ST and the FAB were performed prior to and immediately after an appropriate rTMS session. The active but not sham rTMS induced significant improvement in all ST subtests (word, color, color-word). Conversely, the calculated Stroop interference and the FAB scores remained unchanged. In PD patients, rTMS of the IFG increased the speed of cognitive processing in both the congruent and incongruent conditions of the ST. Copyright © 2011 Movement Disorder Society.

Analysis of mirror neuron system activation during action observation alone and action observation with motor imagery tasks.

PubMed

Cengiz, Bülent; Vurallı, Doğa; Zinnuroğlu, Murat; Bayer, Gözde; Golmohammadzadeh, Hassan; Günendi, Zafer; Turgut, Ali Emre; İrfanoğlu, Bülent; Arıkan, Kutluk Bilge

2018-02-01

This study aimed to explore the relationship between action observation (AO)-related corticomotor excitability changes and phases of observed action and to explore the effects of pure AO and concurrent AO and motor imagery (MI) state on corticomotor excitability using TMS. It was also investigated whether the mirror neuron system activity is muscle-specific. Fourteen healthy volunteers were enrolled in the study. EMG recordings were taken from the right first dorsal interosseous and the abductor digiti minimi muscles. There was a significant main effect of TMS timing (after the beginning of the movement, at the beginning of motor output state, and during black screen) on the mean motor evoked potential (MEP) amplitude. Mean MEP amplitudes for AO combined with MI were significantly higher than pure AO session. There was a significant interaction between session and TMS timing. There was no significant main effect of muscle on MEP amplitude. The results indicate that corticomotor excitability is modulated by different phases of the observed motor movement and this modulation is not muscle-specific. Simultaneous MI and AO enhance corticomotor excitability significantly compared to pure AO.

Cross-Foster Rederivation Compared with Antibiotic Administration in the Drinking Water to Eradicate Bordetella pseudohinzii

PubMed Central

Clark, Sarah E; Purcell, Jeanette E; Bi, Xuan; Fortman, Jeffrey D

2017-01-01

Bordetella pseudohinzii is a microbial agent of potential importance in mice and has confounded pulmonary research at our institution. The purpose of this study was to evaluate cross-foster rederivation and antibiotic administration in the drinking water as methods to eradicate B. pseudohinzii. To evaluate the efficacy of cross-foster rederivation, 29 litters representing 16 strains of mice were cross-fostered from cages positive for B. pseudohinzii to B. pseudohinzii–negative Crl:CD1-Elite surrogate dams. To evaluate antibiotic administration, sulfamethoxazole and trimethoprim (TMS; 0.66 and 0.13 mg/mL, respectively) and tetracycline (4.5 mg/mL) were administered in the drinking water. We assessed 3 antibiotic treatment groups with 12 B. pseudohinzii–positive cages per group (6 cages of CD1 and 6 cages of C57BL/6 mice): TMS for 4 wk, TMS for 6 wk, and tetracycline for 6 wk. Of the 29 litters that underwent cross-foster rederivation, 24 were negative for B. pseudohinzii. Five of the 12 cages treated with TMS for 4 wk and 1 of the 12 cages treated with TMS for 6 wk were negative for B. pseudohinzii at 2 wk after treatment. Three of the 12 cages treated with tetracycline were negative for B. pseudohinzii at 2 wk after treatment. Pearson χ2 analysis revealed significant association between the method of eradication (cross-foster rederivation compared with antibiotic administration) and B. pseudohinzii infection, and an odds-ratio estimate from a logistic regression demonstrated that cross-foster rederivation was more successful. Whereas antibiotic administration in the drinking water failed to eradicate B. pseudohinzii, cross-foster rederivation was successful and has been used to establish a B. pseudohinzii–negative barrier. PMID:28905714

Combined rTMS and virtual reality brain-computer interface training for motor recovery after stroke

NASA Astrophysics Data System (ADS)

Johnson, N. N.; Carey, J.; Edelman, B. J.; Doud, A.; Grande, A.; Lakshminarayan, K.; He, B.

2018-02-01

Objective. Combining repetitive transcranial magnetic stimulation (rTMS) with brain-computer interface (BCI) training can address motor impairment after stroke by down-regulating exaggerated inhibition from the contralesional hemisphere and encouraging ipsilesional activation. The objective was to evaluate the efficacy of combined rTMS  +  BCI, compared to sham rTMS  +  BCI, on motor recovery after stroke in subjects with lasting motor paresis. Approach. Three stroke subjects approximately one year post-stroke participated in three weeks of combined rTMS (real or sham) and BCI, followed by three weeks of BCI alone. Behavioral and electrophysiological differences were evaluated at baseline, after three weeks, and after six weeks of treatment. Main results. Motor improvements were observed in both real rTMS  +  BCI and sham groups, but only the former showed significant alterations in inter-hemispheric inhibition in the desired direction and increased relative ipsilesional cortical activation from fMRI. In addition, significant improvements in BCI performance over time and adequate control of the virtual reality BCI paradigm were observed only in the former group. Significance. When combined, the results highlight the feasibility and efficacy of combined rTMS  +  BCI for motor recovery, demonstrated by increased ipsilesional motor activity and improvements in behavioral function for the real rTMS  +  BCI condition in particular. Our findings also demonstrate the utility of BCI training alone, as shown by behavioral improvements for the sham rTMS  +  BCI condition. This study is the first to evaluate combined rTMS and BCI training for motor rehabilitation and provides a foundation for continued work to evaluate the potential of both rTMS and virtual reality BCI training for motor recovery after stroke.

Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder.

PubMed

Rapinesi, Chiara; Del Casale, Antonio; Di Pietro, Simone; Ferri, Vittoria Rachele; Piacentino, Daria; Sani, Gabriele; Raccah, Ruggero Nessim; Zangen, Abraham; Ferracuti, Stefano; Vento, Alessandro Emiliano; Angeletti, Gloria; Brugnoli, Roberto; D Kotzalidis, Georgios; Girardi, Paolo

2016-08-26

Cocaine dependence is a substantial public health problem. The aim of this study is to evaluate the effect of high frequency deep transcranial magnetic stimulation (dTMS) on craving in patients with cocaine use disorder (CUD). Seven men (mean age, 48.71 years; standard deviation [SD], 9.45; range 32-60 years) with CUD and no concurrent axis 1 or 2 disorder save nicotine abuse, underwent three sessions of alternate day 20Hz dTMS in 20 trains delivered to the dorsolateral prefrontal cortex (DLPFC) preferentially to the left hemisphere, for 12 sessions spread over one month, added to unchanged prior drug treatment. We used a visual analogue scale (VAS) to measure cocaine craving the week before, each week during, and one month after dTMS treatment. DLPFC stimulation significantly reduced craving over time: within-subjects main effect of time of treatment (ANOVA, F[3,18]=46.154; p<0.001; η(2)=0.88). The reduction of craving from baseline was significant at two weeks (p<0.001), and four weeks (p<0.001) of treatment, and at the week eight, four weeks after treatment interruption (p=0.003), although the increase of craving was significant from week four and eight (p=0.014). dTMS over left DLPFC reduced craving in CUD patients in a small sample that is to be considered preliminary. However, maintenance sessions would be needed to maintain the achieved results. Our findings highlight the potential of noninvasive neuromodulation as a therapeutic tool for cocaine addiction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

ceRNAs in plants: computational approaches and associated challenges for target mimic research.

PubMed

Paschoal, Alexandre Rossi; Lozada-Chávez, Irma; Domingues, Douglas Silva; Stadler, Peter F

2017-05-30

The competing endogenous RNA hypothesis has gained increasing attention as a potential global regulatory mechanism of microRNAs (miRNAs), and as a powerful tool to predict the function of many noncoding RNAs, including miRNAs themselves. Most studies have been focused on animals, although target mimic (TMs) discovery as well as important computational and experimental advances has been developed in plants over the past decade. Thus, our contribution summarizes recent progresses in computational approaches for research of miRNA:TM interactions. We divided this article in three main contributions. First, a general overview of research on TMs in plants is presented with practical descriptions of the available literature, tools, data, databases and computational reports. Second, we describe a common protocol for the computational and experimental analyses of TM. Third, we provide a bioinformatics approach for the prediction of TM motifs potentially cross-targeting both members within the same or from different miRNA families, based on the identification of consensus miRNA-binding sites from known TMs across sequenced genomes, transcriptomes and known miRNAs. This computational approach is promising because, in contrast to animals, miRNA families in plants are large with identical or similar members, several of which are also highly conserved. From the three consensus TM motifs found with our approach: MIM166, MIM171 and MIM159/319, the last one has found strong support on the recent experimental work by Reichel and Millar [Specificity of plant microRNA TMs: cross-targeting of mir159 and mir319. J Plant Physiol 2015;180:45-8]. Finally, we stress the discussion on the major computational and associated experimental challenges that have to be faced in future ceRNA studies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Repetitive transcranial magnetic stimulation of the left premotor/dorsolateral prefrontal cortex does not have analgesic effect on central poststroke pain.

PubMed

de Oliveira, Rogério Adas Ayres; de Andrade, Daniel Ciampi; Mendonça, Melina; Barros, Rafael; Luvisoto, Tatiana; Myczkowski, Martin Luiz; Marcolin, Marco Antonio; Teixeira, Manoel Jacobsen

2014-12-01

Central poststroke pain (CPSP) is caused by an encephalic vascular lesion of the somatosensory pathways and is commonly refractory to current pharmacologic treatments. Repetitive transcranial magnetic stimulation (rTMS) of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) can change thermal pain threshold toward analgesia in healthy subjects and has analgesic effects in acute postoperative pain as well as in fibromyalgia patients. However, its effect on neuropathic pain and in CPSP, in particular, has not been assessed. The aim of this prospective, double-blind, placebo-controlled study was to evaluate the analgesic effect of PMC/DLPFC rTMS in CPSP patients. Patients were randomized into 2 groups, active (a-) rTMS and sham (s-) rTMS, and were treated with 10 daily sessions of rTMS over the left PMC/DLPFC (10 Hz, 1,250 pulses/d). Outcomes were assessed at baseline, during the stimulation phase, and at 1, 2, and 4 weeks after the last stimulation. The main outcome was pain intensity changes measured by the visual analog scale on the last stimulation day compared to baseline. Interim analysis was scheduled when the first half of the patients completed the study. The study was terminated because of a significant lack of efficacy of the active arm after 21 patients completed the whole treatment and follow-up phases. rTMS of the left PMC/DLPFC did not improve pain in CPSP. The aim of this double-blind, placebo-controlled study was to evaluate the analgesic effects of rTMS to the PMC/DLPFC in CPSP patients. An interim analysis showed a consistent lack of analgesic effect, and the study was terminated. rTMS of the PMC/DLPFC is not effective in relieving CPSP. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Assessing and inducing neuroplasticity with transcranial magnetic stimulation and robotics for motor function.

PubMed

O'Malley, Marcia K; Ro, Tony; Levin, Harvey S

2006-12-01

To describe 2 new ways of assessing and inducing neuroplasticity in the human brain--transcranial magnetic stimulation (TMS) and robotics--and to investigate and promote the recovery of motor function after brain damage. We identified recent articles and books directly bearing on TMS and robotics. Articles using these tools for purposes other than rehabilitation were excluded. From these studies, we emphasize the methodologic and technical details of these tools as applicable for assessing and inducing plasticity. Because both tools have only recently been used for rehabilitation, the majority of the articles selected for this review have been published only within the last 10 years. We used the PubMed and Compendex databases to find relevant peer-reviewed studies for this review. The studies were required to be relevant to rehabilitation and to use TMS or robotics methodologies. Guidelines were applied via independent extraction by multiple observers. Despite the limited amount of research using these procedures for assessing and inducing neuroplasticity, there is growing evidence that both TMS and robotics can be very effective, inexpensive, and convenient ways for assessing and inducing rehabilitation. Although TMS has primarily been used as an assessment tool for motor function, an increasing number of studies are using TMS as a tool to directly induce plasticity and improve motor function. Similarly, robotic devices have been used for rehabilitation because of their suitability for delivery of highly repeatable training. New directions in robotics-assisted rehabilitation are taking advantage of novel measurements that can be acquired via the devices, enabling unique methods of assessment of motor recovery. As refinements in technology and advances in our knowledge continue, TMS and robotics should play an increasing role in assessing and promoting the recovery of function. Ongoing and future studies combining TMS and robotics within the same populations may prove fruitful for a more detailed and comprehensive assessment of the central and peripheral changes in the nervous system during precisely induced recovery.

Phonological decisions require both the left and right supramarginal gyri.

PubMed

Hartwigsen, Gesa; Baumgaertner, Annette; Price, Cathy J; Koehnke, Maria; Ulmer, Stephan; Siebner, Hartwig R

2010-09-21

Recent functional imaging studies demonstrated that both the left and right supramarginal gyri (SMG) are activated when healthy right-handed subjects make phonological word decisions. However, lesion studies typically report difficulties with phonological processing after left rather than right hemisphere damage. Here, we used a unique dual-site transcranial magnetic stimulation (TMS) approach to test whether the SMG in the right hemisphere contributes to modality-independent (i.e., auditory and visual) phonological decisions. To test task-specificity, we compared the effect of real or sham TMS during phonological, semantic, and perceptual decisions. To test laterality and anatomical specificity, we compared the effect of TMS over the left, right, or bilateral SMG and angular gyri. The accuracy and reaction times of phonological decisions were selectively disrupted relative to semantic and perceptual decisions when real TMS was applied over the left, right, or bilateral SMG. These effects were not observed for TMS over the angular gyri. A follow-up experiment indicated that the threshold-intensity for inducing a disruptive effect on phonological decisions was identical for unilateral TMS over the right or left SMG. Taken together, these findings provide converging evidence that the right SMG contributes to accurate and efficient phonological decisions in the healthy brain, with no evidence that the left and right SMG can compensate for one another during TMS. Our findings motivate detailed studies of phonological processing in patients with acute or long-term damage of the right SMG.

Reliability of TMS metrics in patients with chronic incomplete spinal cord injury.

PubMed

Potter-Baker, K A; Janini, D P; Frost, F S; Chabra, P; Varnerin, N; Cunningham, D A; Sankarasubramanian, V; Plow, E B

2016-11-01

Test-retest reliability analysis in individuals with chronic incomplete spinal cord injury (iSCI). The purpose of this study was to examine the reliability of neurophysiological metrics acquired with transcranial magnetic stimulation (TMS) in individuals with chronic incomplete tetraplegia. Cleveland Clinic Foundation, Cleveland, Ohio, USA. TMS metrics of corticospinal excitability, output, inhibition and motor map distribution were collected in muscles with a higher MRC grade and muscles with a lower MRC grade on the more affected side of the body. Metrics denoting upper limb function were also collected. All metrics were collected at two sessions separated by a minimum of two weeks. Reliability between sessions was determined using Spearman's correlation coefficients and concordance correlation coefficients (CCCs). We found that TMS metrics that were acquired in higher MRC grade muscles were approximately two times more reliable than those collected in lower MRC grade muscles. TMS metrics of motor map output, however, demonstrated poor reliability regardless of muscle choice (P=0.34; CCC=0.51). Correlation analysis indicated that patients with more baseline impairment and/or those in a more chronic phase of iSCI demonstrated greater variability of metrics. In iSCI, reliability of TMS metrics varies depending on the muscle grade of the tested muscle. Variability is also influenced by factors such as baseline motor function and time post SCI. Future studies that use TMS metrics in longitudinal study designs to understand functional recovery should be cautious as choice of muscle and clinical characteristics can influence reliability.

Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of quality of life outcome measures in clinical practice.

PubMed

Janicak, Philip G; Dunner, David L; Aaronson, Scott T; Carpenter, Linda L; Boyadjis, Terrence A; Brock, David G; Cook, Ian A; Lanocha, Karl; Solvason, Hugh B; Bonneh-Barkay, Dafna; Demitrack, Mark A

2013-12-01

Transcranial magnetic stimulation (TMS) is an effective and safe therapy for major depressive disorder (MDD). This study assessed quality of life (QOL) and functional status outcomes for depressed patients after an acute course of TMS. Forty-two, U.S.-based, clinical TMS practice sites treated 307 outpatients with a primary diagnosis of MDD and persistent symptoms despite prior adequate antidepressant pharmacotherapy. Treatment parameters were based on individual clinical considerations and followed the labeled procedures for use of the approved TMS device. Patient self-reported QOL outcomes included change in the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the EuroQol 5-Dimensions (EQ-5D) ratings from baseline to end of the acute treatment phase. Statistically significant improvement in functional status on a broad range of mental health and physical health domains was observed on the SF-36 following acute TMS treatment. Similarly, statistically significant improvement in patient-reported QOL was observed on all domains of the EQ-5D and on the General Health Perception and Health Index scores. Improvement on these measures was observed across the entire range of baseline depression symptom severity. These data confirm that TMS is effective in the acute treatment of MDD in routine clinical practice settings. This symptom benefit is accompanied by statistically and clinically meaningful improvements in patient-reported QOL and functional status outcomes.

Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery

PubMed Central

Liew, Sook-Lei; Santarnecchi, Emilliano; Buch, Ethan R.; Cohen, Leonardo G.

2014-01-01

Non-invasive brain stimulation (NIBS) may enhance motor recovery after neurological injury through the causal induction of plasticity processes. Neurological injury, such as stroke, often results in serious long-term physical disabilities, and despite intensive therapy, a large majority of brain injury survivors fail to regain full motor function. Emerging research suggests that NIBS techniques, such as transcranial magnetic (TMS) and direct current (tDCS) stimulation, in association with customarily used neurorehabilitative treatments, may enhance motor recovery. This paper provides a general review on TMS and tDCS paradigms, the mechanisms by which they operate and the stimulation techniques used in neurorehabilitation, specifically stroke. TMS and tDCS influence regional neural activity underlying the stimulation location and also distant interconnected network activity throughout the brain. We discuss recent studies that document NIBS effects on global brain activity measured with various neuroimaging techniques, which help to characterize better strategies for more accurate NIBS stimulation. These rapidly growing areas of inquiry may hold potential for improving the effectiveness of NIBS-based interventions for clinical rehabilitation. PMID:25018714

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

PubMed Central

Luo, Jing; Zheng, Haiqing; Zhang, Liying; Zhang, Qingjie; Li, Lili; Pei, Zhong; Hu, Xiquan

2017-01-01

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. PMID:28230741

Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

PubMed Central

Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone

2018-01-01

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1’s role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual’s first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and ‘SHAM-VL’), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here. PMID:29630681

Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

PubMed

Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

2018-01-01

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1's role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual's first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and 'SHAM-VL'), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here.

Enhanced Awareness Followed Reversible Inhibition of Human Visual Cortex: A Combined TMS, MRS and MEG Study

PubMed Central

Allen, Christopher P. G.; Dunkley, Benjamin T.; Muthukumaraswamy, Suresh D.; Edden, Richard; Evans, C. John; Sumner, Petroc; Singh, Krish D.; Chambers, Christopher D.

2014-01-01

This series of experiments investigated the neural basis of conscious vision in humans using a form of transcranial magnetic stimulation (TMS) known as continuous theta burst stimulation (cTBS). Previous studies have shown that occipital TMS, when time-locked to the onset of visual stimuli, can induce a phenomenon analogous to blindsight in which conscious detection is impaired while the ability to discriminate ‘unseen’ stimuli is preserved above chance. Here we sought to reproduce this phenomenon using offline occipital cTBS, which has been shown to induce an inhibitory cortical aftereffect lasting 45–60 minutes. Contrary to expectations, our first experiment revealed the opposite effect: cTBS enhanced conscious vision relative to a sham control. We then sought to replicate this cTBS-induced potentiation of consciousness in conjunction with magnetoencephalography (MEG) and undertook additional experiments to assess its relationship to visual cortical excitability and levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA; via magnetic resonance spectroscopy, MRS). Occipital cTBS decreased cortical excitability and increased regional GABA concentration. No significant effects of cTBS on MEG measures were observed, although the results provided weak evidence for potentiation of event related desynchronisation in the β band. Collectively these experiments suggest that, through the suppression of noise, cTBS can increase the signal-to-noise ratio of neural activity underlying conscious vision. We speculate that gating-by-inhibition in the visual cortex may provide a key foundation of consciousness. PMID:24956195

Effects of repetitive transcranial magnetic stimulation combined with sensory cueing on unilateral neglect in subacute patients with right hemispheric stroke: a randomized controlled study.

PubMed

Yang, Nicole Yh; Fong, Kenneth Nk; Li-Tsang, Cecilia Wp; Zhou, D

2017-09-01

To compare the effects of rTMS combined with sensory cueing, rTMS alone, and conventional rehabilitation on unilateral neglect, hemiplegic arm functions and performance of activities of daily living. A single-blinded randomized controlled trial. A convalescent hospital. Sixty inpatients with left unilateral neglect after stroke. Patients were randomly assigned to three groups: rTMS combined with sensory cueing, rTMS, and conventional rehabilitation alone. rTMS at 1 Hz was applied over P5 of the contralesional hemisphere while vibration cueing was emitted using a wristwatch device on the hemiplegic arm, five days per week for two weeks. The first two groups received the same dosage of conventional rehabilitation on top of their experimental interventions. Blinded assessments were administered at baseline, 2 weeks postintervention, and 6 weeks follow-up. Neglect and arm motor performance. Both rTMS combined with sensory cueing (99.6±33.0) and rTMS alone (88.2±28.7) significantly reduced unilateral neglect than conventional rehabilitation (72.7±33.1) when measured using the conventional subtests of the Behavioural Inattention Test, but the combination was better than rTMS alone. Hemiplegic arm functions and activities of daily living improved in all patients across the three groups but no significant differences were found between the groups. The combination of inhibitory P5-rTMS with sensory cueing was better than either rTMS or conventional rehabilitation alone in producing a stronger and long-lasting improvement in unilateral neglect, but the improvement was not associated with improved arm function or independence in activities of daily living.

Predictive value of dorso-lateral prefrontal connectivity for rTMS response in treatment-resistant depression: A brain perfusion SPECT study.

PubMed

Richieri, Raphaëlle; Verger, Antoine; Boyer, Laurent; Boucekine, Mohamed; David, Anthony; Lançon, Christophe; Cermolacce, Michel; Guedj, Eric

2018-05-18

Previous clinical trials have suggested that repetitive transcranial magnetic stimulation (rTMS) has a significant antidepressant effect in patients with treatment resistant depression (TRD). However, results remain heterogeneous with many patients without effective response. The aim of this SPECT study was to determine before treatment the predictive value of the connectivity of the stimulated area on further rTMS response in patients with TRD. Fifty-eight TRD patients performed a brain perfusion SPECT before high frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). A voxel based-analysis was achieved to compare connectivity of the left DLPFC in responders and non-responders using inter-regional correlations (p < 0.005, corrected for cluster volume). A multiple logistic regression model was thereafter used with the goal of establishing a predictive score. Before rTMS, responders exhibited increased SPECT connectivity between the left DLPFC and the right cerebellum in comparison to non-responders, independently of age, gender, severity of depression, and severity of treatment resistance. The area under the curve for the combination of these two SPECT clusters to predict rTMS response was 0.756 (p < 0.005). SPECT connectivity of the left DLPFC predicts rTMS response before treatment. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Modulating Brain Connectivity by Simultaneous Dual-Mode Stimulation over Bilateral Primary Motor Cortices in Subacute Stroke Patients.

PubMed

Lee, Jungsoo; Park, Eunhee; Lee, Ahee; Chang, Won Hyuk; Kim, Dae-Shik; Shin, Yong-Il; Kim, Yun-Hee

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has been used for the modulation of stroke patients' motor function. Recently, more challenging approaches have been studied. In this study, simultaneous stimulation using both rTMS and tDCS (dual-mode stimulation) over bilateral primary motor cortices (M1s) was investigated to compare its modulatory effects with single rTMS stimulation over the ipsilesional M1 in subacute stroke patients. Twenty-four patients participated; 12 participants were assigned to the dual-mode stimulation group while the other 12 participants were assigned to the rTMS-only group. We assessed each patient's motor function using the Fugl-Meyer assessment score and acquired their resting-state fMRI data at two times: prior to stimulation and 2 months after stimulation. Twelve healthy subjects were also recruited as the control group. The interhemispheric connectivity of the contralesional M1, interhemispheric connectivity between bilateral hemispheres, and global efficiency of the motor network noticeably increased in the dual-mode stimulation group compared to the rTMS-only group. Contrary to the dual-mode stimulation group, there was no significant change in the rTMS-only group. These data suggested that simultaneous dual-mode stimulation contributed to the recovery of interhemispheric interaction than rTMS only in subacute stroke patients. This trial is registered with NCT03279640.

Modulating Brain Connectivity by Simultaneous Dual-Mode Stimulation over Bilateral Primary Motor Cortices in Subacute Stroke Patients

PubMed Central

Park, Eunhee; Lee, Ahee; Chang, Won Hyuk; Kim, Dae-Shik

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has been used for the modulation of stroke patients' motor function. Recently, more challenging approaches have been studied. In this study, simultaneous stimulation using both rTMS and tDCS (dual-mode stimulation) over bilateral primary motor cortices (M1s) was investigated to compare its modulatory effects with single rTMS stimulation over the ipsilesional M1 in subacute stroke patients. Twenty-four patients participated; 12 participants were assigned to the dual-mode stimulation group while the other 12 participants were assigned to the rTMS-only group. We assessed each patient's motor function using the Fugl-Meyer assessment score and acquired their resting-state fMRI data at two times: prior to stimulation and 2 months after stimulation. Twelve healthy subjects were also recruited as the control group. The interhemispheric connectivity of the contralesional M1, interhemispheric connectivity between bilateral hemispheres, and global efficiency of the motor network noticeably increased in the dual-mode stimulation group compared to the rTMS-only group. Contrary to the dual-mode stimulation group, there was no significant change in the rTMS-only group. These data suggested that simultaneous dual-mode stimulation contributed to the recovery of interhemispheric interaction than rTMS only in subacute stroke patients. This trial is registered with NCT03279640. PMID:29666636

Associations between clinical outcome and navigated transcranial magnetic stimulation characteristics in patients with motor-eloquent brain lesions: a combined navigated transcranial magnetic stimulation-diffusion tensor imaging fiber tracking approach.

PubMed

Sollmann, Nico; Wildschuetz, Noémie; Kelm, Anna; Conway, Neal; Moser, Tobias; Bulubas, Lucia; Kirschke, Jan S; Meyer, Bernhard; Krieg, Sandro M

2018-03-01

OBJECTIVE Navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging fiber tracking (DTI FT) based on nTMS data are increasingly used for preoperative planning and resection guidance in patients suffering from motor-eloquent brain tumors. The present study explores whether nTMS-based DTI FT can also be used for individual preoperative risk assessment regarding surgery-related motor impairment. METHODS Data derived from preoperative nTMS motor mapping and subsequent nTMS-based tractography in 86 patients were analyzed. All patients suffered from high-grade glioma (HGG), low-grade glioma (LGG), or intracranial metastasis (MET). In this context, nTMS-based DTI FT of the corticospinal tract (CST) was performed at a range of fractional anisotropy (FA) levels based on an individualized FA threshold ([FAT]; tracking with 50%, 75%, and 100% FAT), which was defined as the highest FA value allowing for visualization of fibers (100% FAT). Minimum lesion-to-CST distances were measured, and fiber numbers of the reconstructed CST were assessed. These data were then correlated with the preoperative, postoperative, and follow-up status of motor function and the resting motor threshold (rMT). RESULTS At certain FA levels, a statistically significant difference in lesion-to-CST distances was observed between patients with HGG who had no impairment and those who developed surgery-related transient or permanent motor deficits (75% FAT: p = 0.0149; 100% FAT: p = 0.0233). In this context, no patient with a lesion-to-CST distance ≥ 12 mm suffered from any new surgery-related permanent paresis (50% FAT and 75% FAT). Furthermore, comparatively strong negative correlations were observed between the rMT and lesion-to-CST distances of patients with surgery-related transient paresis (Spearman correlation coefficient [r s ]; 50% FAT: r s = -0.8660; 75% FAT: r s = -0.8660) or surgery-related permanent paresis (50% FAT: r s = -0.7656; 75% FAT: r s = -0.6763). CONCLUSIONS This is one of the first studies to show a direct correlation between imaging, clinical status, and neurophysiological markers for the integrity of the motor system in patients with brain tumors. The findings suggest that nTMS-based DTI FT might be suitable for individual risk assessment in patients with HGG, in addition to being a surgery-planning tool. Importantly, necessary data for risk assessment were obtained without significant additional efforts, making this approach potentially valuable for direct clinical use.

Interhemispheric modulation of dual-mode, noninvasive brain stimulation on motor function.

PubMed

Park, Eunhee; Kim, Yun-Hee; Chang, Won Hyuk; Kwon, Tae Gun; Shin, Yong-Il

2014-06-01

To investigate the effects of simultaneous, bihemispheric, dual-mode stimulation using repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on motor functions and cortical excitability in healthy individuals. Twenty-five healthy, right-handed volunteers (10 men, 15 women; mean age, 25.5 years) were enrolled. All participants received four randomly arranged, dual-mode, simultaneous stimulations under the following conditions: condition 1, high-frequency rTMS over the right primary motor cortex (M1) and sham tDCS over the left M1; condition 2, high-frequency rTMS over the right M1 and anodal tDCS over the left M1; condition 3, high-frequency rTMS over the right M1 and cathodal tDCS over the left M1; and condition 4, sham rTMS and sham tDCS. The cortical excitability of the right M1 and motor functions of the left hand were assessed before and after each simulation. Motor evoked potential (MEP) amplitudes after stimulation were significantly higher than before stimulation, under the conditions 1 and 2. The MEP amplitude in condition 2 was higher than both conditions 3 and 4, while the MEP amplitude in condition 1 was higher than condition 4. The results of the Purdue Pegboard test and the box and block test showed significant improvement in conditions 1 and 2 after stimulation. Simultaneous stimulation by anodal tDCS over the left M1 with high-frequency rTMS over the right M1 could produce interhemispheric modulation and homeostatic plasticity, which resulted in modulation of cortical excitability and motor functions.

A common neural substrate for language production and verbal working memory.

PubMed

Acheson, Daniel J; Hamidi, Massihullah; Binder, Jeffrey R; Postle, Bradley R

2011-06-01

Verbal working memory (VWM), the ability to maintain and manipulate representations of speech sounds over short periods, is held by some influential models to be independent from the systems responsible for language production and comprehension [e.g., Baddeley, A. D. Working memory, thought, and action. New York, NY: Oxford University Press, 2007]. We explore the alternative hypothesis that maintenance in VWM is subserved by temporary activation of the language production system [Acheson, D. J., & MacDonald, M. C. Verbal working memory and language production: Common approaches to the serial ordering of verbal information. Psychological Bulletin, 135, 50-68, 2009b]. Specifically, we hypothesized that for stimuli lacking a semantic representation (e.g., nonwords such as mun), maintenance in VWM can be achieved by cycling information back and forth between the stages of phonological encoding and articulatory planning. First, fMRI was used to identify regions associated with two different stages of language production planning: the posterior superior temporal gyrus (pSTG) for phonological encoding (critical for VWM of nonwords) and the middle temporal gyrus (MTG) for lexical-semantic retrieval (not critical for VWM of nonwords). Next, in the same subjects, these regions were targeted with repetitive transcranial magnetic stimulation (rTMS) during language production and VWM task performance. Results showed that rTMS to the pSTG, but not the MTG, increased error rates on paced reading (a language production task) and on delayed serial recall of nonwords (a test of VWM). Performance on a lexical-semantic retrieval task (picture naming), in contrast, was significantly sensitive to rTMS of the MTG. Because rTMS was guided by language production-related activity, these results provide the first causal evidence that maintenance in VWM directly depends on the long-term representations and processes used in speech production.

Interhemispheric Connectivity Influences the Degree of Modulation of TMS-Induced Effects during Auditory Processing

PubMed Central

Andoh, Jamila; Zatorre, Robert J.

2011-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been shown to interfere with many components of language processing, including semantic, syntactic, and phonologic. However, not much is known about its effects on nonlinguistic auditory processing, especially its action on Heschl's gyrus (HG). We aimed to investigate the behavioral and neural basis of rTMS during a melody processing task, while targeting the left HG, the right HG, and the Vertex as a control site. Response times (RT) were normalized relative to the baseline-rTMS (Vertex) and expressed as percentage change from baseline (%RT change). We also looked at sex differences in rTMS-induced response as well as in functional connectivity during melody processing using rTMS and functional magnetic resonance imaging (fMRI). fMRI results showed an increase in the right HG compared with the left HG during the melody task, as well as sex differences in functional connectivity indicating a greater interhemispheric connectivity between left and right HG in females compared with males. TMS results showed that 10 Hz-rTMS targeting the right HG induced differential effects according to sex, with a facilitation of performance in females and an impairment of performance in males. We also found a differential correlation between the %RT change after 10 Hz-rTMS targeting the right HG and the interhemispheric functional connectivity between right and left HG, indicating that an increase in interhemispheric functional connectivity was associated with a facilitation of performance. This is the first study to report a differential rTMS-induced interference with melody processing depending on sex. In addition, we showed a relationship between the interference induced by rTMS on behavioral performance and the neural activity in the network connecting left and right HG, suggesting that the interhemispheric functional connectivity could determine the degree of modulation of behavioral performance. PMID:21811478

The Impact of Diffusion Tensor Imaging Fiber Tracking of the Corticospinal Tract Based on Navigated Transcranial Magnetic Stimulation on Surgery of Motor-Eloquent Brain Lesions.

PubMed

Raffa, Giovanni; Conti, Alfredo; Scibilia, Antonino; Cardali, Salvatore Massimiliano; Esposito, Felice; Angileri, Filippo Flavio; La Torre, Domenico; Sindorio, Carmela; Abbritti, Rosaria Viola; Germanò, Antonino; Tomasello, Francesco

2017-11-29

Navigated transcranial magnetic stimulation (nTMS) enables preoperative mapping of the motor cortex (M1). The combination of nTMS with diffusion tensor imaging fiber tracking (DTI-FT) of the corticospinal tract (CST) has been described; however, its impact on surgery of motor-eloquent lesions has not been addressed. To analyze the impact of nTMS-based mapping on surgery of motor-eloquent lesions. In this retrospective case-control study, we reviewed the data of patients operated for suspected motor-eloquent lesions between 2012 and 2015. The patients underwent nTMS mapping of M1 and, from 2014, nTMS-based DTI-FT of the CST. The impact on the preoperative risk/benefit analysis, surgical strategy, craniotomy size, extent of resection (EOR), and outcome were compared with a control group. We included 35 patients who underwent nTMS mapping of M1 (group A), 35 patients who also underwent nTMS-based DTI-FT of the CST (group B), and a control group composed of 35 patients treated without nTMS (group C). The patients in groups A and B received smaller craniotomies (P = .01; P = .001), had less postoperative seizures (P = .02), and a better postoperative motor performance (P = .04) and Karnofsky Performance Status (P = .009) than the controls. Group B exhibited an improved risk/benefit analysis (P = .006), an increased EOR of nTMS-negative lesions in absence of preoperative motor deficits (P = .01), and less motor and Karnofsky Performance Status worsening in case of preoperative motor deficits (P = .02, P = .03) than group A. nTMS-based mapping enables a tailored surgical approach for motor-eloquent lesions. It may improve the risk/benefit analysis, EOR and outcome, particularly when nTMS-based DTI-FT is performed. Copyright © 2017 by the Congress of Neurological Surgeons

TMS Suppression of Right Pars Triangularis, but Not Pars Opercularis, Improves Naming in Aphasia

ERIC Educational Resources Information Center

Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro

2011-01-01

This study sought to discover if an optimum 1 cm[squared] area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in…

Placebo Response in Repetitive Transcranial Magnetic Stimulation Trials of Treatment of Auditory Hallucinations in Schizophrenia: A Meta-Analysis

PubMed Central

Dollfus, Sonia; Lecardeur, Laurent; Morello, Rémy; Etard, Olivier

2016-01-01

Several meta-analyses have assessed the response of patients with schizophrenia with auditory verbal hallucinations (AVH) to treatment with repetitive transcranial magnetic stimulation (rTMS); however, the placebo response has never been explored. Typically observed in a therapeutic trial, the placebo effect may have a major influence on the effectiveness of rTMS. The purpose of this meta-analysis is to evaluate the magnitude of the placebo effect observed in controlled studies of rTMS treatment of AVH, and to determine factors that can impact the magnitude of this placebo effect, such as study design considerations and the type of sham used. The study included twenty-one articles concerning 303 patients treated by sham rTMS. A meta-analytic method was applied to obtain a combined, weighted effect size, Hedges’s g. The mean weighted effect size of the placebo effect across these 21 studies was 0.29 (P < .001). Comparison of the parallel and crossover studies revealed distinct results for each study design; placebo has a significant effect size in the 13 parallel studies (g = 0.44, P < 10−4), but not in the 8 crossover studies (g = 0.06, P = .52). In meta-analysis of the 13 parallel studies, the 45° position coil showed the highest effect size. Our results demonstrate that placebo effect should be considered a major source of bias in the assessment of rTMS efficacy. These results fundamentally inform the design of further controlled studies, particularly with respect to studies of rTMS treatment in psychiatry. PMID:26089351

A Lack of Clinical Effect of High-frequency rTMS to Dorsolateral Prefrontal Cortex on Bulimic Symptoms: A Randomised, Double-blind Trial.

PubMed

Gay, Aurelia; Jaussent, Isabelle; Sigaud, Torrance; Billard, Stephane; Attal, Jerome; Seneque, Maude; Galusca, Bogdan; Van Den Eynde, Frederique; Massoubre, Catherine; Courtet, Philippe; Guillaume, Sebastien

2016-11-01

Studies suggest that stimulation of the left dorsolateral prefrontal cortex (DLPFC) reduces food craving in bulimic patients, but evidence supporting repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool is lacking. We investigated the safety and therapeutic efficacy of an adjunct high-frequency rTMS programme targeting the left DLPFC. Forty-seven women with bulimia nervosa were randomised to a real or sham stimulation group. The real group underwent 10 rTMS sessions, each consisting of 20 trains of 5 seconds with 55-second intervals between trains, at a frequency of 10 Hz. The main outcome was the number of binge episodes in the 15 days following the end of stimulation. Overall, no significant improvement in bingeing and purging symptoms was noted after the programme. rTMS was well tolerated. This suggests that 10 sessions of high-frequency rTMS to the left DLPFC provide no greater benefit than placebo. Future studies should consider methodological issues as well as alternative targets. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Transcranial magnetic stimulation: language function.

PubMed

Epstein, C M

1998-07-01

Studies of language using transcranial magnetic stimulation (TMS) have focused both on identification of language areas and on elucidation of function. TMS may result in either inhibition or facilitation of language processes and may operate directly at a presumptive site of language cortex or indirectly through intracortical networks. TMS has been used to create reversible "temporary lesions," similar to those produced by Wada tests and direct cortical electrical stimulation, in cerebral cortical areas subserving language function. Rapid-rate TMS over the left inferior frontal region blocks speech output in most subjects. However, the results are not those predicted from classic models of language organization. Speech arrest is obtained most easily over facial motor cortex, and true aphasia is rare, whereas right hemisphere or bilateral lateralization is unexpectedly prominent. A clinical role for these techniques is not yet fully established. Interfering with language comprehension and verbal memory is currently more difficult than blocking speech output, but numerous TMS studies have demonstrated facilitation of language-related tasks, including oral word association, story recall, digit span, and picture naming. Conversely, speech output also facilitates motor responses to TMS in the dominant hemisphere. Such new and often-unexpected findings may provide important insights into the organization of language.

Relationships of Behavioral Measures of Frontal Lobe Dysfunction with Underlying Electrophysiology in Cocaine-Dependent Patients

PubMed Central

Gjini, Klevest; Qazi, Aisha; Greenwald, Mark K.; Sandhu, Ravinder; Gooding, Diane C.; Boutros, Nash N.

2013-01-01

Background and Objectives Despite evidence that frontal lobe functioning is impaired in cocaine-dependent individuals, relationships between behavioral measures of frontal dysfunction and electrophysiological measures of inhibition in cocaine use have not been explored. Methods Using the Frontal System Behavior Scale (FrSBe), frontal dysfunction was assessed in a group of abstinent cocaine-dependent subjects (N=49) and healthy controls (N=32). Using transcranial magnetic stimulation (TMS) and evoked potential (EP)-based electrophysiological measures of inhibition, we assessed associations between these measures and FrSBe estimates of frontal dysfunction. Results Patients had significantly higher FrSBe scores for executive dysfunction, disinhibition and apathy than controls. Lower TMS-based resting motor thresholds (i.e., hyperexcitability) were significantly associated with higher Executive Dysfunction scores in the patients. Conclusions and Scientific Significance Relationships between FrSBe scores and TMS-based measures highlight neurophysiological aberrations underlying frontal lobe dysfunction in cocaine abusers. TMS and EP measures may be useful probes of the intermediary steps between frontal lobe dysfunction and addictive behavior. PMID:24724884

TMS affects moral judgment, showing the role of DLPFC and TPJ in cognitive and emotional processing.

PubMed

Jeurissen, Danique; Sack, Alexander T; Roebroeck, Alard; Russ, Brian E; Pascual-Leone, Alvaro

2014-01-01

Decision-making involves a complex interplay of emotional responses and reasoning processes. In this study, we use TMS to explore the neurobiological substrates of moral decisions in humans. To examining the effects of TMS on the outcome of a moral-decision, we compare the decision outcome of moral-personal and moral-impersonal dilemmas to each other and examine the differential effects of applying TMS over the right DLPFC or right TPJ. In this comparison, we find that the TMS-induced disruption of the DLPFC during the decision process, affects the outcome of the moral-personal judgment, while TMS-induced disruption of TPJ affects only moral-impersonal conditions. In other words, we find a double-dissociation between DLPFC and TPJ in the outcome of a moral decision. Furthermore, we find that TMS-induced disruption of the DLPFC during non-moral, moral-impersonal, and moral-personal decisions lead to lower ratings of regret about the decision. Our results are in line with the dual-process theory and suggest a role for both the emotional response and cognitive reasoning process in moral judgment. Both the emotional and cognitive processes were shown to be involved in the decision outcome.

Network-wise cerebral blood flow redistribution after 20 Hz rTMS on left dorso-lateral prefrontal cortex.

PubMed

Shang, Yuan-Qi; Xie, Jun; Peng, Wei; Zhang, Jian; Chang, Da; Wang, Ze

2018-04-01

The repetitive application of transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) has been consistently shown to be beneficial for treating various neuropsychiatric or neuropsychological disorders, but its neural mechanisms still remain unclear. The purpose of this study was to measure the effects of high-frequency left DLPFC rTMS using cerebral blood flow (CBF) collected from 40 young healthy subjects before and after applying 20 Hz left DLPFC rTMS or SHAM stimulations. Relative CBF (rCBF) changes before and after 20 Hz rTMS or SHAM were assessed with paired-t test. The results show that 20 Hz DLPFC rTMS induced CBF redistribution in the default mode network, including increased rCBF in left medial temporal cortex (MTC)/hippocampus, but reduced rCBF in precuneus and cerebellum. Meanwhile, SHAM stimulation didn't produce any rCBF changes. After controlling SHAM effects, only the rCBF increase in MTC/hippocampus remained. Those data suggest that the beneficial effects of high-frequency rTMS may be through a within-network rCBF redistribution. Copyright © 2018 Elsevier B.V. All rights reserved.

Long-lasting repetitive transcranial magnetic stimulation modulates electroencephalography oscillation in patients with disorders of consciousness.

PubMed

Xia, Xiaoyu; Liu, Yang; Bai, Yang; Liu, Ziyuan; Yang, Yi; Guo, Yongkun; Xu, Ruxiang; Gao, Xiaorong; Li, Xiaoli; He, Jianghong

2017-10-18

Repetitive transcranial magnetic stimulation (rTMS) has been applied for the treatment of patients with disorders of consciousness (DOC). Timely and accurate assessments of its modulation effects are very useful. This study evaluated rTMS modulation effects on electroencephalography (EEG) oscillation in patients with chronic DOC. Eighteen patients with a diagnosis of DOC lasting more than 3 months were recruited. All patients received one session of 10-Hz rTMS at the left dorsolateral prefrontal cortex and then 12 of them received consecutive rTMS treatment everyday for 20 consecutive days. Resting-state EEGs were recorded before the experiment (T0) after one session of rTMS (T1) and after the entire treatment (T2). The JFK Coma Recovery Scale-Revised scale scores were also recorded at the time points. Our data showed that application of 10-Hz rTMS to the left dorsolateral prefrontal cortex decreased low-frequency band power and increased high-frequency band power in DOC patients, especially in minimal conscious state patients. Considering the correlation of the EEG spectrum with the consciousness level of patients with DOC, quantitative EEG might be useful for assessment of the effect of rTMS in DOC patients.

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

PubMed

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 Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation for Improving Apathy in Chronic Stroke Patients.

PubMed

Sasaki, Nobuyuki; Hara, Takatoshi; Yamada, Naoki; Niimi, Masachika; Kakuda, Wataru; Abo, Masahiro

2017-01-01

Although repetitive transcranial magnetic stimulation (rTMS) for hemiparesis is beneficial, so far no study has examined the usefulness of rTMS for apathy. Thirteen patients with chronic stroke were assigned randomly to 2 groups: rTMS group (n = 7) and sham stimulation group (n = 6). The patients received 5 sessions of either high-frequency rTMS over the region spanning from the dorsal anterior cingulate cortex (dACC) to medial prefrontal cortex (mPFC) or sham stimulation for 5 days. The severity of apathy was evaluated using the Apathy Scale (AS) and the severity of depression was evaluated using the Quick Inventory of Depressive Symptomatology (QIDS) serially before and after the 5-day protocol. The AS and QIDS scores were significantly improved in the rTMS group, although they were not changed in the sham stimulation group. The degree of change in the AS score was significantly greater in the rTMS group than that in the sham stimulation group. The degree of change in the QIDS score was greater in the rTMS group than that in the sham stimulation group, although the difference was not statistically significant. The application of high frequency rTMS over the dACC and mPFC may be a useful intervention for apathy due to stroke. © 2017 S. Karger AG, Basel.

High-Performance Lithium-Oxygen Battery Electrolyte Derived from Optimum Combination of Solvent and Lithium Salt.

PubMed

Ahn, Su Mi; Suk, Jungdon; Kim, Do Youb; Kang, Yongku; Kim, Hwan Kyu; Kim, Dong Wook

2017-10-01

To fabricate a sustainable lithium-oxygen (Li-O 2 ) battery, it is crucial to identify an optimum electrolyte. Herein, it is found that tetramethylene sulfone (TMS) and lithium nitrate (LiNO 3 ) form the optimum electrolyte, which greatly reduces the overpotential at charge, exhibits superior oxygen efficiency, and allows stable cycling for 100 cycles. Linear sweep voltammetry (LSV) and differential electrochemical mass spectrometry (DEMS) analyses reveal that neat TMS is stable to oxidative decomposition and exhibit good compatibility with a lithium metal. But, when TMS is combined with typical lithium salts, its performance is far from satisfactory. However, the TMS electrolyte containing LiNO 3 exhibits a very low overpotential, which minimizes the side reactions and shows high oxygen efficiency. LSV-DEMS study confirms that the TMS-LiNO 3 electrolyte efficiently produces NO 2 - , which initiates a redox shuttle reaction. Interestingly, this NO 2 - /NO 2 redox reaction derived from the LiNO 3 salt is not very effective in solvents other than TMS. Compared with other common Li-O 2 solvents, TMS seems optimum solvent for the efficient use of LiNO 3 salt. Good compatibility with lithium metal, high dielectric constant, and low donicity of TMS are considered to be highly favorable to an efficient NO 2 - /NO 2 redox reaction, which results in a high-performance Li-O 2 battery.

[The neuronal level of motor activity: determination of motor cortex excitability by TMS].

PubMed

Eichhammer, Peter; Langguth, Berthold; Müller, Jürgen; Hajak, Göran

2005-04-01

Transcranial magnetic stimulation as mapping method offers the possibility to measure aspects of motor cortex excitability painlessly and non-invasively. Using this neurophysiological tool, new insights into the effects of central-acting drugs are possible. Particularly striking seems to be the potential of this approach to gain new insights into neurobiological processes associated with neuropsychiatric diseases like schizophrenia or major depression. In combination with genetic aspects, TMS is able to bridge the gap between molecular research and clinical approach.

The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI.

PubMed

Plow, Ela B; Cattaneo, Zaira; Carlson, Thomas A; Alvarez, George A; Pascual-Leone, Alvaro; Battelli, Lorella

2014-01-01

A balance of mutual tonic inhibition between bi-hemispheric posterior parietal cortices is believed to play an important role in bilateral visual attention. However, experimental support for this notion has been mainly drawn from clinical models of unilateral damage. We have previously shown that low-frequency repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a contralateral attentional deficit in bilateral visual tracking. Here, we used functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily disrupts the inter-hemispheric balance between bilateral IPS in visual attention. Following application of 1 Hz rTMS over the left IPS, subjects performed a bilateral visual tracking task while their brain activity was recorded using fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS. Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL), lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL), Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal areas (MT+), showed higher activity. The brain activity of the homologues of these regions in the un-stimulated, right hemisphere was reversed. Interestingly, the evolution of network-wide activation related to attentional behavior following rTMS showed that activation of most occipital synergists adaptively compensated for contralateral and ipsilateral decrement after rTMS, while activation of parietal synergists, and SoG remained competing. This pattern of ipsilateral and contralateral activations empirically supports the hypothesized loss of inter-hemispheric balance that underlies clinical manifestation of visual attentional extinction.

Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes.

PubMed

André-Obadia, N; Mertens, P; Gueguen, A; Peyron, R; Garcia-Larrea, L

2008-09-09

To assess, against placebo, the pain-relieving effects of high-rate repetitive transcranial magnetic stimulation (rTMS) on neuropathic pain. Double-blind, randomized, cross-over study of high-rate rTMS against placebo in 28 patients. The effect of a change in coil orientation (posteroanterior vs lateromedial) on different subtypes of neuropathic pain was further tested in a subset of 16 patients. Pain relief was evaluated daily during 1 week. High-frequency, posteroanterior rTMS decreased pain scores significantly more than placebo. Posteroanterior rTMS also outmatched placebo in a score combining subjective (pain relief, quality of life) and objective (rescue drug intake) criteria of treatment benefit. Changing the orientation of the coil from posteroanterior to lateromedial did not yield any significant pain relief. The analgesic effects of posteroanterior rTMS lasted for approximately 1 week. The pain-relieving effects were observed exclusively on global scores reflecting the most distressing type of pain in each patient. Conversely, rTMS did not modify specifically any of the pain subscores that were separately tested (ongoing, paroxysmal, stimulus-evoked, or disesthesic pain). Posteroanterior repetitive transcranial magnetic stimulation (rTMS) was more effective than both placebo and lateromedial rTMS. When obtained, pain relief was not specific of any particular submodality, but rather reduced the global pain sensation whatever its type. This is in accord with recent models of motor cortex neurostimulation, postulating that its analgesic effects may derive in part from modulation of the affective appraisal of pain, rather than a decrease of its sensory components.

A single session of repetitive transcranial magnetic stimulation of the prefrontal cortex reduces cue-induced craving in patients with gambling disorder.

PubMed

Gay, A; Boutet, C; Sigaud, T; Kamgoue, A; Sevos, J; Brunelin, J; Massoubre, C

2017-03-01

Gambling disorder (GD) is common and disabling addictive disorder. In patients with substance use disorders, the application of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers promise to alleviate craving. We hypothesized that applying real compared to sham rTMS over the left DLPFC would reduce gambling craving in patients with GD. In a randomized sham-controlled crossover design, 22 treatment-seeking patients with GD received real or sham treatment with high frequency rTMS over the left DLPFC followed a week later by the other type of treatment. Before and after each rTMS session, participants rated their gambling craving (from 0 to 100) before and after viewing a gambling video used as a cue. We used the Yale-Brown Obsessive Compulsive Scale adapted for Pathological Gambling to assess gambling behavior before and 7 days after each rTMS session. As compared to sham (mean +0.74; standard deviation±3.03), real rTMS significantly decreased cue-induced craving (-2.12±3.39; F (1,19) =4.87; P=0.04; partial η 2 =0.05; 95% CI: 0.00-0.21). No significant effect of rTMS was observed on gambling behavior. Patients with GD reported decreased cue-induced craving following a single session of high frequency rTMS applied over the left DLPFC. Further large randomized controlled studies are needed to determine the usefulness of rTMS in GD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Non-invasive mapping of bilateral motor speech areas using navigated transcranial magnetic stimulation and functional magnetic resonance imaging.

PubMed

Könönen, Mervi; Tamsi, Niko; Säisänen, Laura; Kemppainen, Samuli; Määttä, Sara; Julkunen, Petro; Jutila, Leena; Äikiä, Marja; Kälviäinen, Reetta; Niskanen, Eini; Vanninen, Ritva; Karjalainen, Pasi; Mervaala, Esa

2015-06-15

Navigated transcranial magnetic stimulation (nTMS) is a modern precise method to activate and study cortical functions noninvasively. We hypothesized that a combination of nTMS and functional magnetic resonance imaging (fMRI) could clarify the localization of functional areas involved with motor control and production of speech. Navigated repetitive TMS (rTMS) with short bursts was used to map speech areas on both hemispheres by inducing speech disruption during number recitation tasks in healthy volunteers. Two experienced video reviewers, blinded to the stimulated area, graded each trial offline according to possible speech disruption. The locations of speech disrupting nTMS trials were overlaid with fMRI activations of word generation task. Speech disruptions were produced on both hemispheres by nTMS, though there were more disruptive stimulation sites on the left hemisphere. Grade of the disruptions varied from subjective sensation to mild objectively recognizable disruption up to total speech arrest. The distribution of locations in which speech disruptions could be elicited varied among individuals. On the left hemisphere the locations of disturbing rTMS bursts with reviewers' verification followed the areas of fMRI activation. Similar pattern was not observed on the right hemisphere. The reviewer-verified speech disruptions induced by nTMS provided clinically relevant information, and fMRI might explain further the function of the cortical area. nTMS and fMRI complement each other, and their combination should be advocated when assessing individual localization of speech network. Copyright © 2015 Elsevier B.V. All rights reserved.

Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study.

PubMed

Sahlsten, Hanna; Virtanen, Juuso; Joutsa, Juho; Niinivirta-Joutsa, Katri; Löyttyniemi, Eliisa; Johansson, Reijo; Paavola, Janika; Taiminen, Tero; Sjösten, Noora; Salonen, Jaakko; Holm, Anu; Rauhala, Esa; Jääskeläinen, Satu K

2017-09-01

Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). Thirty-nine patients (mean age 50.3 years). The mean tinnitus intensity (F 3  = 15.7, p < 0.0001), annoyance (F 3  = 8.8, p = 0.0002), distress (F 3  = 9.1, p = 0.0002) and THI scores (F 4  = 13.8, p < 0.0001) decreased in both groups over time with non-significant differences between the groups. After active rTMS, 42% and 37% of the patients showed excellent response at 1 and 3 months against 15% and 10% in the placebo group (p = 0.082 and p = 0.065). Despite the significant effects of rTMS on tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation.

Cost-effectiveness of electroconvulsive therapy compared to repetitive transcranial magnetic stimulation for treatment-resistant severe depression: a decision model.

PubMed

Vallejo-Torres, L; Castilla, I; González, N; Hunter, R; Serrano-Pérez, P; Perestelo-Pérez, L

2015-05-01

Electroconvulsive therapy (ECT) is widely applied to treat severe depression resistant to standard treatment. Results from previous studies comparing the cost-effectiveness of this technique with treatment alternatives such as repetitive transcranial magnetic stimulation (rTMS) are conflicting. We conducted a cost-effectiveness analysis comparing ECT alone, rTMS alone and rTMS followed by ECT when rTMS fails under the perspective of the Spanish National Health Service. The analysis is based on a Markov model which simulates the costs and health outcomes of individuals treated under these alternatives over a 12-month period. Data to populate this model were extracted and synthesized from a series of randomized controlled trials and other studies that have compared these techniques on the patient group of interest. We measure effectiveness using quality-adjusted life years (QALYs) and characterize the uncertainty using probabilistic sensitivity analyses. ECT alone was found to be less costly and more effective than rTMS alone, while the strategy of providing rTMS followed by ECT when rTMS fails is the most expensive and effective option. The incremental cost per QALY gained of this latter strategy was found to be above the reference willingness-to-pay threshold used in these types of studies in Spain and other countries. The probability that ECT alone is the most cost-effective alternative was estimated to be around 70%. ECT is likely to be the most cost-effective option in the treatment of resistant severe depression for a willingness to pay of €30,000 per QALY.

Modulating phonemic fluency performance in healthy subjects with transcranial magnetic stimulation over the left or right lateral frontal cortex.

PubMed

Smirni, Daniela; Turriziani, Patrizia; Mangano, Giuseppa Renata; Bracco, Martina; Oliveri, Massimiliano; Cipolotti, Lisa

2017-07-28

A growing body of evidence have suggested that non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can improve the performance of aphasic patients in language tasks. For example, application of inhibitory rTMS or tDCs over the right frontal lobe of dysphasic patients resulted in improved naming abilities. Several studies have also reported that in healthy controls (HC) tDCS application over the left prefrontal cortex (PFC) improve performance in naming and semantic fluency tasks. The aim of this study was to investigate in HC, for the first time, the effects of inhibitory repetitive TMS (rTMS) over left and right lateral frontal cortex (BA 47) on two phonemic fluency tasks (FAS or FPL). 44 right-handed HCs were administered rTMS or sham over the left or right lateral frontal cortex in two separate testing sessions, with a 24h interval, followed by the two phonemic fluency tasks. To account for possible practice effects, an additional 22 HCs were tested on only the phonemic fluency task across two sessions with no stimulation. We found that rTMS-inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance when compared to sham. In contrast, rTMS-inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance when compared to sham. These results were not accounted for practice effects. We speculated that rTMS over the right lateral frontal cortex may induce plastic neural changes to the left lateral frontal cortex by suppressing interhemispheric inhibitory interactions. This resulted in an increased excitability (disinhibition) of the contralateral unstimulated left lateral frontal cortex, consequently enhancing phonemic fluency performance. Conversely, application of rTMS over the left lateral frontal cortex may induce a temporary, virtual lesion, with effects similar to those reported in left frontal patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS.

PubMed

Richieri, Raphaëlle; Boyer, Laurent; Padovani, Romain; Adida, Marc; Colavolpe, Cécile; Mundler, Olivier; Lançon, Christophe; Guedj, Eric

2012-12-03

Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics. This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS). 99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10Hz) left-side stimulation in 33 patients, and low frequency (1Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p<0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation. Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p=0.017) or right stimulation (p<0.001), without significant perfusion differences between these two subgroups. These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group. Copyright © 2012 Elsevier Inc. All rights reserved.

[What is the purpose of the German Aptitude Test for Medical Studies (TMS)?].

PubMed

Kadmon, Guni; Kirchner, Anna; Duelli, Roman; Resch, Franz; Kadmon, Martina

2012-01-01

The German Aptitude Test for Medical Studies (TMS) was implemented in 2007. 12,194 persons registered for this test in 2011, which represents a 91% increase over 2007. The male/female ratio remained constant at 38:62. Its reliability among applicants to Heidelberg Medical Faculty was confirmed by Cronbach's α (≥ 0.75) and inter-item correlation (≥ 0.25, p < 10(-7)). The TMS contains nine items; using factor analysis these were allocated to the two components verbal-mathematical and spatial-figural ability. The verbal-mathematical items moderately correlate with the German Baccalaureate GPA (r = 0.33), while the spatial-figural items do not correlate (r = 0.07). Thus, the TMS is an admission instrument that appraise different cognitive abilities than the GPA. For the admission of students to our faculty their TMS scores are weighted at 39%, which has resulted in a diversification of our student cohorts. Copyright © 2011. Published by Elsevier GmbH.

A proof-of-concept study on the combination of repetitive transcranial magnetic stimulation and relaxation techniques in chronic tinnitus.

PubMed

Kreuzer, Peter M; Poeppl, Timm B; Bulla, Jan; Schlee, Winfried; Lehner, Astrid; Langguth, Berthold; Schecklmann, Martin

2016-10-01

Interference of ongoing neuronal activity and brain stimulation motivated this study to combine repetitive transcranial magnetic stimulation (rTMS) and relaxation techniques in tinnitus patients. Forty-two patients were enrolled in this one-arm proof-of-concept study to receive ten sessions of rTMS applied to the left dorsolateral prefrontal cortex and temporo-parietal cortex. During stimulation, patients listened to five different kinds of relaxation audios. Variables of interest were tinnitus questionnaires, tinnitus numeric rating scales, depressivity, and quality of life. Results were compared to results of historical control groups having received the same rTMS protocol (active control) and sham treatment (placebo) without relaxation techniques. Thirty-eight patients completed the treatment, drop-out rates and adverse events were low. Responder rates (reduction in tinnitus questionnaire (TQ) score ≥5 points 10 weeks after treatment) were 44.7 % in the study, 27.8 % in the active control group, and 21.7 % in the placebo group, differing between groups on a near significant level. For the tinnitus handicap inventory (THI), the main effect of group was not significant. However, linear mixed model analyses showed that the relaxation/rTMS group differed significantly from the active control group showing steeper negative THI trend for the relaxation/rTMS group indicating better amelioration over the course of the trial. Deepness of relaxation during rTMS and selection of active relaxation vs. passive listening to music predicted larger TQ. All remaining secondary outcomes turned out non-significant. This combined treatment proved to be a safe, feasible and promising approach to enhance rTMS treatment effects in chronic tinnitus.

Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in Schizophrenia Patients with Predominant Negative Symptoms: An Exploratory Study.

PubMed

Dlabac-de Lange, Jozarni J; Liemburg, Edith J; Bais, Leonie; van de Poel-Mustafayeva, Aida T; de Lange-de Klerk, Elly S M; Knegtering, Henderikus; Aleman, André

Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism. This study aims to investigate changes in the levels of glutamate and glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate (NAA) in the left dorsolateral prefrontal cortex of patients with schizophrenia treated with active bilateral prefrontal rTMS as compared to sham-rTMS, as measured with 1 H-Magnetic Resonance Spectroscopy ( 1 H-MRS). Patients were randomized to a 3-week course of active or sham high-frequency rTMS. Pre-treatment and post-treatment 1 H-MRS data were available for 24 patients with schizophrenia with moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale ≥ 15). Absolute metabolite concentrations were calculated using LCModel with the water peak as reference. To explore the association between treatment condition and changes in concentration of Glx and NAA, we applied a linear regression model. We observed an increase of Glx concentration in the active treatment group and a decrease of Glx concentration in the group receiving sham treatment. The association between changes in Glx concentration and treatment condition was significant. No significant associations between changes in NAA and treatment condition were found. Noninvasive neurostimulation with high-frequency bilateral prefrontal rTMS may influence Glx concentration in the prefrontal cortex of patients with schizophrenia. Larger studies are needed to confirm these findings and further elucidate the underlying neural working mechanism of rTMS. Copyright © 2016 Elsevier Inc. All rights reserved.

Follow-up study of children whose mothers were treated with transcranial magnetic stimulation during pregnancy: preliminary results.

PubMed

Eryılmaz, Gul; Sayar, Gökben Hızlı; Özten, Eylem; Gül, Işıl Göğcegöz; Yorbik, Özgür; Işiten, Nuket; Bağcı, Eda

2015-06-01

The purpose of this study is to determine the impact of repetitive transcranial stimulation (rTMS) treatment during pregnancy on neurodevelopment of children. Women who were treated with rTMS during pregnancy and delivered liveborn children between 2008 and 2013 were selected. A control group consisted of children whose mothers had a history of untreated depression during their pregnancy (N = 26). Early developmental characteristics of all the children in the study were evaluated, and their developmental levels were determined using the Ankara Developmental Screening Inventory. The mean age of the children in the rTMS treatment group was 32.4 months (range 16-64 months), and that of the untreated group was 29.04 (range 14-63 months). Jaundice (N = 2) and febrile convulsion (N = 1) were the reported medical conditions in the children of the rTMS-treated group; jaundice (N = 3) and low birth weight (N = 1) were reported in the untreated group. In the rTMS group, mothers' perception of delay in language development was observed, but there were not any statistically significant differences in the prevalence rate compared with the untreated group (OR = 0.38; 95% CI 0.0860-1.6580). Our results suggest that rTMS exposure during pregnancy is not associated with poorer cognitive or motor development outcomes in children aged 18-62 months. Although language development as reported by the mothers was found to be poorer than expected in the rTMS-treated group, the delay was found to be similar to the language delay observed in offspring of untreated mothers, as reported in previous studies of prenatal depression treated with selective serotonin reuptake inhibitors. © 2014 International Neuromodulation Society.

Establishing an effective TMS protocol for craving in substance addiction: Is it possible?

PubMed

Enokibara, Mailu; Trevizol, Alisson; Shiozawa, Pedro; Cordeiro, Quirino

2016-01-01

Repetitive transcranial magnetic stimulation (TMS) is a non-invasive tool with known therapeutic efficacy in various neuropsychiatric disorders, such as depression, schizophrenia, mania, and anxiety disorders. We hereby, briefly present a brief review and meta-analysis on the use of TMS for craving in substance addiction. We present our brief review and meta-analysis following the recommendations of the Cochrane group. A total of eight randomized controlled trials fulfilled eligibility criteria and were selected. A total of 199 patients were studied. We found active stimulation to be superior than sham protocols only for trials focused on right DLPFC (with Hedge's g = 1.48; ES (95%CI: 0.126-2.834), p = 0.032. Main meta-analysis limitations include small number of studies, high heterogeneity among studies, and high publication bias. However challenging, our exploratory analysis underscored the amelioration of craving in substance addiction for trials using high frequency TMS protocols over the right DLPFC. We hereby, propose the use of this particular TMS protocol as a promising tool in clinical research. © American Academy of Addiction Psychiatry.

An investigation into the induced electric fields from transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Hadimani, Ravi; Lee, Erik; Duffy, Walter; Waris, Mohammed; Siddiqui, Waquar; Islam, Faisal; Rajamani, Mahesh; Nathan, Ryan; Jiles, David; David C Jiles Team; Walter Duffy Collaboration

Transcranial magnetic stimulation (TMS) is a promising tool for noninvasive brain stimulation that has been approved by the FDA for the treatment of major depressive disorder. To stimulate the brain, TMS uses large, transient pulses of magnetic field to induce an electric field in the head. This transient magnetic field is large enough to cause the depolarization of cortical neurons and initiate a synaptic signal transmission. For this study, 50 unique head models were created from MRI images. Previous simulation studies have primarily used a single head model, and thus give a limited image of the induced electric field from TMS. This study uses finite element analysis simulations on 50 unique, heterogeneous head models to better investigate the relationship between TMS and the electric field induced in brain tissues. Results showed a significant variation in the strength of the induced electric field in the brain, which can be reasonably predicted by the distance from the TMS coil to the stimulated brain. Further, it was seen that some models had high electric field intensities in over five times as much brain volume as other models.

Repetitive transcranial magnetic stimulation induced modulations of resting state motor connectivity in writer's cramp.

PubMed

Bharath, R D; Biswal, B B; Bhaskar, M V; Gohel, S; Jhunjhunwala, K; Panda, R; George, L; Gupta, A K; Pal, P K

2015-05-01

Writer's cramp (WC) is a focal task-specific dystonia of the hand which is increasingly being accepted as a network disorder. Non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsfMRI). Nineteen patients with right-sided WC and 20 matched healthy controls (HCs) were prospectively evaluated. All patients underwent a single session of rTMS and rsfMRI was acquired before (R1) and after (R2) rTMS. Seed-based functional connectivity analysis of several regions in the motor network was performed for HCs, R1 and R2 using SPM8 software. Thresholded (P < 0.05, false discovery rate corrected) group level mean correlation maps were used to derive significantly connected region of interest pairs. Writer's cramp showed a significant reduction in resting state functional connectivity in comparison with HCs involving the left cerebellum, thalamus, globus pallidus, putamen, bilateral supplementary motor area, right medial prefrontal lobe and right post central gyrus. After rTMS there was a significant increase in the contralateral resting state functional connectivity through the left thalamus-right globus pallidus-right thalamus-right prefrontal lobe network loop. It is concluded that WC is a network disorder with widespread dysfunction much larger than clinically evident and changes induced by rTMS probably act through subcortical and trans-hemispheric unaffected connections. Longitudinal studies with therapeutic rTMS will be required to ascertain whether such information could be used to select patients prior to rTMS therapy. © 2015 EAN.

Improvements in hand function in adults with chronic tetraplegia following a multi-day 10Hz rTMS intervention combined with repetitive task practice

PubMed Central

Gomes-Osman, Joyce; Field-Fote, Edelle C.

2014-01-01

Background and Purpose Evidence suggests the use of stimulation to increase corticomotor excitability improves hand function in persons with cervical spinal cord injury (SCI). We assessed effects of multi-day application of 10Hz repetitive transcranial magnetic stimulation (rTMS) applied to the corticomotor hand area combined with repetitive task practice (RTP) in participants with tetraplegia and neurologically healthy participants. Methods Using a double-blind randomized crossover design, 11 participants with chronic tetraplegia and 10 neurologically healthy participants received 3 sessions of 10Hz rTMS+RTP and 3 sessions of sham-rTMS+RTP to the corticomotor hand region controlling the weaker hand. RTMS was interleaved with RTP of a skilled motor task between pulse trains. Hand function (Jebsen-Taylor Hand Function Test [JTT], pinch, and grasp strength) and corticomotor excitability (amplitude of motor-evoked potential) were assessed prior to and following the rTMS+RTP and sham-rTMS+RTP phases. We assessed significance using paired t-tests on pre-post differences and effect sizes using standardized response mean (SRM). Results RTMS+RTP was associated with larger effect sizes compared to sham-rTMS+RTP for improvement in JTT for both the trained hand (SRM=0.85 and 0.42, respectively), non-trained hand (0.55, 0.31, respectively), and for grasp strength of the trained hand in the SCI group (0.67, 0.39, respectively) alone. Effect sizes for all other measures were small and there were no statistical between-condition differences in the outcomes assessed. Discussion and Conclusions RTMS may be a valuable adjunct to RTP for improving hand function in persons with tetraplegia. Higher stimulation dose (frequency, intensity, number of sessions) may be associated with larger effects. Video Abstract available (See Supplemental Digital Conent 1) for more insights from the authors. PMID:25415549

Intracortical inhibition in the human trigeminal motor system.

PubMed

Jaberzadeh, Shapour; Pearce, Sophie L; Miles, Timothy S; Türker, Kemal S; Nordstrom, Michael A

2007-08-01

To investigate the presence and features of short-interval intracortical inhibition (SICI) in the human trigeminal motor system. Surface electromyogram (EMG) was recorded from left and right digastric muscles in 7 subjects, along with additional experiments with intramuscular EMG in 2 subjects. Focal transcranial magnetic stimulation (TMS) was used to activate the motor cortex of one hemisphere and elicit motor evoked potentials (MEPs) in digastric muscles on each side, at rest and while subjects activated the muscles at 10% maximal EMG. Paired or single TMS pulses were delivered in blocks of trials, while conditioning TMS intensity and interstimulus interval (ISI) were varied. At rest, paired TMS (3-ms ISI) with conditioning intensities 0.8-0.9x active motor threshold (TA) reduced the digastric MEP amplitude to a similar extent bilaterally. Conditioning at 0.5-0.7TA did not significantly reduce the MEP. MEP amplitude was reduced to a similar extent in both digastric muscles by ISIs between 1 and 4 ms (0.8TA). Voluntary bilateral activation of digastric muscles reduced the effectiveness of conditioning TMS compared to the resting state, with no differences between sides. The similarity of the responses in both digastric muscles was not due to EMG cross-talk (estimated to be approximately 10% in surface records and approximately 2% in intramuscular records), as the intramuscular records showed the same pattern as the surface records. The effects of paired-pulse TMS on digastric are similar to those reported for contralateral hand muscles, and are consistent with activation of SICI circuits in M1 by conditioning TMS. Our evidence further suggests that the corticomotor representations of left and right digastric muscles in M1 of a single hemisphere receive analogous inhibitory modulation from SICI circuits. SICI has been demonstrated in the face area of motor cortex controlling the trigeminal motor system in normal subjects. This method can be used to investigate abnormalities of SICI in movement disorders affecting the masticatory muscles in humans.

Do drug metabolism and pharmacokinetic departments make any contribution to drug discovery?

PubMed

Smith, Dennis; Schmid, Esther; Jones, Barry

2002-01-01

The alignment of drug metabolism and pharmacokinetic departments with drug discovery has not produced a radical improvement in the pharmacokinetic properties of new chemical entities. The reason for this is complex, reflecting in part the difficulty of combining potency, selectivity, water solubility, metabolic stability and membrane permeability into a single molecule. This combination becomes increasingly problematic as the drug targets become more distant from aminergic seven-transmembrane-spanning receptors (7-TMs). The leads available for aminergic 7-TMs, like the natural agonists, are invariably small molecular weight, water soluble and potent. Even moving to 7-TMs for which the agonist is a peptide invariably produces lead matter that is less drug-like (higher molecular weight and lipophilic). The role of drug metabolism departments, therefore, has been to guide chemistry to obtaining adequate, rather than optimal, pharmacokinetic properties for these 'difficult' drug targets. A consistent belief of many researchers is that a high value is placed on optimal, rather than adequate, pharmacokinetic properties. One measure of value is market sales, and when these are examined no clear pattern emerges. Part of the success of amlodipine in the calcium channel antagonist sector must be due to its excellent pharmacokinetic profile, but the best-selling drugs among the angiotensin antagonists and beta-blockers have a much greater market share than other agents with better pharmacokinetic properties. Clearly, many other factors are important in the successful launch of a medicine, some reflected in the manner the compound is developed and the subsequent structure of the labelling. Overall, therefore the presence of drug metabolism in drug discovery has probably contributed most by allowing 'difficult' drug targets to be prosecuted, rather than by guiding medicinal chemists to optimal pharmacokinetics. These 'difficult' target candidates become successful drugs when skilfully developed. There is no doubt that skilful development relies heavily on drug metabolism and pharmacokinetic departments, in this case those with a clinical rather than a preclinical orientation.

Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

PubMed Central

Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

2014-01-01

Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies. PMID:24917788

BOREAS Level-0 ER-2 Daedalus TMS Imagery Digital Counts in BIL Format

NASA Technical Reports Server (NTRS)

Newcomer, Jeffrey A.; Dominguez, Roseanne; Hall, Forrest G. (Editor)

2000-01-01

The level-0 Daedalus Thematic Mapper Simulator (TMS) imagery, along with the other remotely sensed images, was collected to provide spatially extensive information about radiant energy over the primary BOReal Ecosystem-Atmosphere Study (BOREAS) study areas. This information includes detailed land cover and biophysical parameter maps such as fraction of Photosynthetically Active Radiation (fPAR) and Leaf Area Index (LAI). Two flights of the Daedalus TMS instrument were made onboard the ER-2 aircraft on 16-Sep-1994 and 17-Sep-1994.

A chronometric exploration of high-resolution 'sensitive TMS masking' effects on subjective and objective measures of vision.

PubMed

de Graaf, Tom A; Herring, Jim; Sack, Alexander T

2011-03-01

Transcranial magnetic stimulation (TMS) can induce masking by interfering with ongoing neural activity in early visual cortex. Previous work has explored the chronometry of occipital involvement in vision by using single pulses of TMS with high temporal resolution. However, conventionally TMS intensities have been high and the only measure used to evaluate masking was objective in nature. Recent studies have begun to incorporate subjective measures of vision, alongside objective ones. The current study goes beyond previous work in two regards. First, we explored both objective vision (an orientation discrimination task) and subjective vision (a stimulus visibility rating on a four-point scale), across a wide range of time windows with high temporal resolution. Second, we used a very sensitive TMS-masking paradigm: stimulation was at relatively low TMS intensities, with a figure-8 coil, and the small stimulus was difficult to discriminate already at baseline level. We hypothesized that this should increase the effective temporal resolution of our paradigm. Perhaps for this reason, we are able to report a rather interesting masking curve. Within the classical-masking time window, previously reported to encompass broad SOAs anywhere between 60 and 120 ms, we report not one, but at least two dips in objective performance, with no masking in-between. The subjective measure of vision did not mirror this pattern. These preliminary data from our exploratory design suggest that, with sensitive TMS masking, we might be able to reveal visual processes in early visual cortex previously unreported.

rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

PubMed Central

Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

2013-01-01

Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

Preliminary Upper Estimate of Peak Currents in Transcranial Magnetic Stimulation at Distant Locations from a TMS Coil

PubMed Central

Makarov, Sergey N.; Yanamadala, Janakinadh; Piazza, Matthew W.; Helderman, Alex M.; Thang, Niang S.; Burnham, Edward H.; Pascual-Leone, Alvaro

2016-01-01

Goals Transcranial magnetic stimulation (TMS) is increasingly used as a diagnostic and therapeutic tool for numerous neuropsychiatric disorders. The use of TMS might cause whole-body exposure to undesired induced currents in patients and TMS operators. The aim of the present study is to test and justify a simple analytical model known previously, which may be helpful as an upper estimate of eddy current density at a particular distant observation point for any body composition and any coil setup. Methods We compare the analytical solution with comprehensive adaptive mesh refinement-based FEM simulations of a detailed full-body human model, two coil types, five coil positions, about 100,000 observation points, and two distinct pulse rise times, thus providing a representative number of different data sets for comparison, while also using other numerical data. Results Our simulations reveal that, after a certain modification, the analytical model provides an upper estimate for the eddy current density at any location within the body. In particular, it overestimates the peak eddy currents at distant locations from a TMS coil by a factor of 10 on average. Conclusion The simple analytical model tested in the present study may be valuable as a rapid method to safely estimate levels of TMS currents at different locations within a human body. Significance At present, safe limits of general exposure to TMS electric and magnetic fields are an open subject, including fetal exposure for pregnant women. PMID:26685221

Language mapping with navigated transcranial magnetic stimulation in pediatric and adult patients undergoing epilepsy surgery: Comparison with extraoperative direct cortical stimulation.

PubMed

Lehtinen, Henri; Mäkelä, Jyrki P; Mäkelä, Teemu; Lioumis, Pantelis; Metsähonkala, Liisa; Hokkanen, Laura; Wilenius, Juha; Gaily, Eija

2018-06-01

Navigated transcranial magnetic stimulation (nTMS) is becoming increasingly popular in noninvasive preoperative language mapping, as its results correlate well enough with those obtained by direct cortical stimulation (DCS) during awake surgery in adult patients with tumor. Reports in the context of epilepsy surgery or extraoperative DCS in adults are, however, sparse, and validation of nTMS with DCS in children is lacking. Furthermore, little is known about the risk of inducing epileptic seizures with nTMS in pediatric epilepsy patients. We provide the largest validation study to date in an epilepsy surgery population. We compared language mapping with nTMS and extraoperative DCS in 20 epilepsy surgery patients (age range 9-32 years; 14 children and adolescents). In comparison with DCS, sensitivity of nTMS was 68%, specificity 76%, positive predictive value 27%, and negative predictive value 95%. Age, location of ictal-onset zone near or within DCS-mapped language areas or severity of cognitive deficits had no significant effect on these values. None of our patients had seizures during nTMS. Our study suggests that nTMS language mapping is clinically useful and safe in epilepsy surgery patients, including school-aged children and patients with extensive cognitive dysfunction. Similar to in tumor surgery, mapping results in the frontal region are most reliable. False negative findings may be slightly more likely in epilepsy than in tumor surgery patients. Mapping results should always be verified by other methods in individual patients.

Super-hydrophobic multilayer coatings with layer number tuned swapping in surface wettability and redox catalytic anti-corrosion application.

PubMed

Syed, Junaid Ali; Tang, Shaochun; Meng, Xiangkang

2017-06-30

The wetting characteristic of a metal surface can be controlled by employing different coating materials and external stimuli, however, layer number (n) modulated surface swapping between hydrophobicity and hydrophilicity in a multilayer structure to achieve prolonged anti-corrosion ability was not taken into consideration. In this study, we proposed a layer-by-layer (LbL) spin assembled polyaniline-silica composite/tetramethylsilane functionalized silica nanoparticles (PSC/TMS-SiO 2 ) coating with the combined effect of super-hydrophobicity and enhanced anti-corrosion ability. Interestingly, the hierarchical integration of two coating materials with inherently different surface roughness and energy in a multilayer structure allows the wetting feature to swap from hydrophobic to hydrophilic state by modulating n with decreasing hydrophilicity. The samples with odd n (TMS-SiO 2 surface) are hydrophobic while the samples with even n (PSC surface) exhibits the hydrophilic character. The TMS-SiO 2 content was optimized to achieve super-hydrophobic coating with significantly high water contact angle (CA) 153° ± 2° and small sliding angle (SA) 6° ± 2°. Beside its self-cleaning behavior, the electro-active PSC/TMS-SiO 2 coating also exhibits remarkably enhanced corrosion resistance against aggressive media. The corrosion resistance of the coating was remained stable even after 240 h of exposure, this enhancement is attributed to super-hydrophobicity and anodic shift in corrosion potential.

Treatment for Traumatic Brain Injury in Mice Using Transcranial Magnetic Stimulation: A Preliminary Study

NASA Astrophysics Data System (ADS)

Carr, Alexandria; Zenitsky, Gary; Crowther, Lawrence; Hadimani, Ravi; Anantharam, Vellareddy; Kanthasamy, Anumantha; Jiles, David

2014-03-01

Transcranial magnetic stimulation (TMS) is a non-invasive surgery-free tool used to stimulate the brain by time-varying magnetic fields. TMS is currently being investigated as a treatment for neurological disorders such as depression, Parkinson's disease and TBI. Before moving to human TMS/TBI trials, animal testing should be pursued to determine suitability and adverse effects. As an initial study, four healthy mice were treated with TMS at different power levels to determine short-term behavioral effects and set a control group baseline. The mouse's behavior was studied using the Rotorod test, which measures the animal's latency to fall off a rotating rod, and the Versamax test, which measures horizontal and vertical movement, and total distance traveled. The Rotorod test has shown for TMS power levels >=90% the mice begin to fall directly post-treatment. Similarly, the Versamax test has shown for power levels >=80% the mice are less mobile directly post-treatment. Versamax mobility was found to return to normal the day following treatment. These mice were housed in the facility for 4 months and the behavioral tests were repeated. Versamax results showed there was no significant variation in mobility indicating there are no long-term side effects of TMS treatment on the mice. This work was supported by the Barbara and James Palmer Endowment and the Carver Charitable Trust at the Department of Electrical and Computer Engineering, Iowa State University.

A comparison of the usefulness of canonical analysis, principal components analysis, and band selection for extraction of features from TMS data for landcover analysis

NASA Technical Reports Server (NTRS)

Boyd, R. K.; Brumfield, J. O.; Campbell, W. J.

1984-01-01

Three feature extraction methods, canonical analysis (CA), principal component analysis (PCA), and band selection, have been applied to Thematic Mapper Simulator (TMS) data in order to evaluate the relative performance of the methods. The results obtained show that CA is capable of providing a transformation of TMS data which leads to better classification results than provided by all seven bands, by PCA, or by band selection. A second conclusion drawn from the study is that TMS bands 2, 3, 4, and 7 (thermal) are most important for landcover classification.

Dissociating Contributions of the Motor Cortex to Speech Perception and Response Bias by Using Transcranial Magnetic Stimulation

PubMed Central

Smalle, Eleonore H. M.; Rogers, Jack; Möttönen, Riikka

2015-01-01

Recent studies using repetitive transcranial magnetic stimulation (TMS) have demonstrated that disruptions of the articulatory motor cortex impair performance in demanding speech perception tasks. These findings have been interpreted as support for the idea that the motor cortex is critically involved in speech perception. However, the validity of this interpretation has been called into question, because it is unknown whether the TMS-induced disruptions in the motor cortex affect speech perception or rather response bias. In the present TMS study, we addressed this question by using signal detection theory to calculate sensitivity (i.e., d′) and response bias (i.e., criterion c). We used repetitive TMS to temporarily disrupt the lip or hand representation in the left motor cortex. Participants discriminated pairs of sounds from a “ba”–“da” continuum before TMS, immediately after TMS (i.e., during the period of motor disruption), and after a 30-min break. We found that the sensitivity for between-category pairs was reduced during the disruption of the lip representation. In contrast, disruption of the hand representation temporarily reduced response bias. This double dissociation indicates that the hand motor cortex contributes to response bias during demanding discrimination tasks, whereas the articulatory motor cortex contributes to perception of speech sounds. PMID:25274987

Teachable moments for health behavior change and intermediate patient outcomes.

PubMed

Flocke, Susan A; Clark, Elizabeth; Antognoli, Elizabeth; Mason, Mary Jane; Lawson, Peter J; Smith, Samantha; Cohen, Deborah J

2014-07-01

Teachable moments (TM) are opportunities created through physician-patient interaction and used to encourage patients to change unhealthy behaviors. We examine the effectiveness of TMs to increase patients' recall of advice, motivation to modify behavior, and behavior change. A mixed-method observational study of 811 patient visits to 28 primary care clinicians used audio-recordings of visits to identify TMs and other types of advice in health behavior change talk. Patient surveys assessed smoking, exercise, fruit/vegetable consumption, height, weight, and readiness for change prior to the observed visit and 6-weeks post-visit. Compared to other identified categories of advice (i.e. missed opportunities or teachable moment attempts), recall was greatest after TMs occurred (83% vs. 49-74%). TMs had the greatest proportion of patients change in importance and confidence and increase readiness to change; however differences were small. TMs had greater positive behavior change scores than other categories of advice; however, this pattern was statistically non-significant and was not observed for BMI change. TMs have a greater positive influence on several intermediate markers of patient behavior change compared to other categories of advice. TMs show promise as an approach for clinicians to discuss behavior change with patients efficiently and effectively. Copyright © 2014. Published by Elsevier Ireland Ltd.

Effect of high-frequency repetitive transcranial magnetic stimulation on major depressive disorder in patients with Parkinson's disease.

PubMed

Shin, Hae-Won; Youn, Young C; Chung, Sun J; Sohn, Young H

2016-07-01

Major depressive disorder (MDD) occurs in a small proportion of patients with Parkinson's disease (PD) and reduces their quality of life. We performed a randomized sham-controlled study to evaluate the effect of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) on MDD in patients with PD. Ten patients participated to a real-rTMS group and eight patients to a sham-rTMS group. Evaluations were performed at baseline, 2 and 6 weeks after rTMS treatment. All participants underwent examinations of depression rating scales, including the Hamilton Rating Scale, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Beck Depression Inventory (BDI) and the motor part of the Unified Parkinson Disease Rating Scale (UPDRS-III). The real-rTMS group had improved scores on HRS and the MADRS after 10 sessions, and these beneficial effects persisted for 6 weeks after the initial session. The BDI score did not change immediately after the sessions. The sham-rTMS group had no significant changes in any of the depression rating scales. The UPDRS-III did not change in either group. HF-rTMS of the left DLPFC is an effective treatment for MDD in patients with PD.

A cortical substrate for the long-term memory of saccadic eye movements calibration.

PubMed

Pélisson, Denis; Habchi, Ouazna; Panouillères, Muriel T N; Hernoux, Charles; Farnè, Alessandro

2018-06-19

How movements are continuously adapted to physiological and environmental changes is a fundamental question in systems neuroscience. While many studies have elucidated the mechanisms which underlie short-term sensorimotor adaptation (∼10-30 min), how these motor memories are maintained over longer-term (>3-5 days) -and thanks to which neural systems-is virtually unknown. Here, we examine in healthy human participants whether the temporo-parietal junction (TPJ) is causally involved in the induction and/or the retention of saccadic eye movements' adaptation. Single-pulse transcranial magnetic stimulation (spTMS) was applied while subjects performed a ∼15min size-decrease adaptation task of leftward reactive saccades. A TMS pulse was delivered over the TPJ in the right hemisphere (rTPJ) in each trial either 30, 60, 90 or 120 msec (in 4 separate adaptation sessions) after the saccade onset. In two control groups of subjects, the same adaptation procedure was achieved either alone (No-TMS) or combined with spTMS applied over the vertex (SHAM-TMS). While the timing of spTMS over the rTPJ did not significantly affect the speed and immediate after-effect of adaptation, we found that the amount of adaptation retention measured 10 days later was markedly larger (42%) than in both the No-TMS (21%) and the SHAM-TMS (11%) control groups. These results demonstrate for the first time that the cerebral cortex is causally involved in maintaining long-term oculomotor memories. Copyright © 2018. Published by Elsevier Inc.

Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression.

PubMed

McClintock, Shawn M; Reti, Irving M; Carpenter, Linda L; McDonald, William M; Dubin, Marc; Taylor, Stephan F; Cook, Ian A; O'Reardon, John; Husain, Mustafa M; Wall, Christopher; Krystal, Andrew D; Sampson, Shirlene M; Morales, Oscar; Nelson, Brent G; Latoussakis, Vassilios; George, Mark S; Lisanby, Sarah H

To provide expert recommendations for the safe and effective application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). Participants included a group of 17 expert clinicians and researchers with expertise in the clinical application of rTMS, representing both the National Network of Depression Centers (NNDC) rTMS Task Group and the American Psychiatric Association Council on Research (APA CoR) Task Force on Novel Biomarkers and Treatments. The consensus statement is based on a review of extensive literature from 2 databases (OvidSP MEDLINE and PsycINFO) searched from 1990 through 2016. The search terms included variants of major depressive disorder and transcranial magnetic stimulation. The results were limited to articles written in English that focused on adult populations. Of the approximately 1,500 retrieved studies, a total of 118 publications were included in the consensus statement and were supplemented with expert opinion to achieve consensus recommendations on key issues surrounding the administration of rTMS for MDD in clinical practice settings. In cases in which the research evidence was equivocal or unclear, a consensus decision on how rTMS should be administered was reached by the authors of this article and is denoted in the article as "expert opinion." Multiple randomized controlled trials and published literature have supported the safety and efficacy of rTMS antidepressant therapy. These consensus recommendations, developed by the NNDC rTMS Task Group and APA CoR Task Force on Novel Biomarkers and Treatments, provide comprehensive information for the safe and effective clinical application of rTMS in the treatment of MDD. © Copyright 2017 Physicians Postgraduate Press, Inc.

The efficacy and safety of low frequency repetitive transcranial magnetic stimulation for treatment-resistant depression: the results from a large multicenter French RCT.

PubMed

Brunelin, Jerome; Jalenques, Isabelle; Trojak, Benoit; Attal, Jerome; Szekely, David; Gay, Aurélia; Januel, Dominique; Haffen, Emmanuel; Schott-Pethelaz, Anne-Marie; Brault, Coralie; Poulet, Emmanuel

2014-01-01

The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD). In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n = 55), active rTMS combined with placebo venlafaxine (n = 60) or sham rTMS combined with active venlafaxine (n = 55). The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS17 score <8. We reported a similar significant antidepressant effect in the 3 groups (P < 10(-6)), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; P = 0.59). Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 min) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD. Copyright © 2014 Elsevier Inc. All rights reserved.

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder.

PubMed

Philip, Noah S; Barredo, Jennifer; van 't Wout-Frank, Mascha; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L

2018-02-01

Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD. Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation. More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes. These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders. Published by Elsevier Inc.

Real-time measurement of cerebral blood flow during and after repetitive transcranial magnetic stimulation: A near-infrared spectroscopy study.

PubMed

Park, Eunhee; Kang, Min Jae; Lee, Ahee; Chang, Won Hyuk; Shin, Yong-Il; Kim, Yun-Hee

2017-07-13

To confirm the interhemispheric modulation induced by low-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex, real-time regional cerebral blood flow (rCBF) was assessed using functional near-infrared spectroscopy (fNIRS) in the contralateral primary motor cortex (M1) and premotor cortex (PM). Ten right-handed healthy subjects completed two experimental sessions that were randomly arranged for real or sham rTMS session. In the real rTMS session, fNIRS data were acquired from the right M1 and PM area, while the motor hot spot of the left M1 was stimulated with 1Hz rTMS for 1200 pulses with two boosters. In the sham stimulation session, stimulation was delivered with a disconnected coil. During the real rTMS session, the concentration of oxyhemoglobin ([oxy-Hb]) in the right M1 increased continuously until the end of the stimulation. These changes lasted for 20min, while the right PM did not show a change in [oxy-Hb] concentration. On the other hand, the concentration of deoxy-hemoglobin ([deoxy-Hb]) decreased continuously in the right M1 and PM during the real rTMS stimulation, and this change lasted for 20min after the stimulation. The sham stimulation did not exhibit any significant change in both [oxy-Hb] and [deoxy-Hb] concentration during or after the stimulation. Application of 1Hz rTMS over M1 resulted in changes of rCBF in contralateral M1 and PM, which seemed to constitute a function of interhemispheric modulation of rTMS. The fNIRS data was able to detect this physiological change of neuromodulatory action of rTMS in real-time. Copyright © 2017. Published by Elsevier B.V.

Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rTMS

PubMed Central

Dunlop, Katharine; Woodside, Blake; Olmsted, Marion; Colton, Patricia; Giacobbe, Peter; Downar, Jonathan

2016-01-01

Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of nonresponse to conventional treatments. OCD pathophysiology is believed to involve abnormalities in cortico-striatal-thalamic-cortical circuits through regions such as dorsomedial prefrontal cortex (dmPFC) and ventral striatum. These regions may constitute therapeutic targets for neuromodulation treatments, such as repetitive transcranial magnetic stimulation (rTMS). However, the neurobiological predictors and correlates of successful rTMS treatment for OCD are unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) to identify neural predictors and correlates of response to 20–30 sessions of bilateral 10 Hz dmPFC-rTMS in 20 treatment-resistant OCD patients, with 40 healthy controls as baseline comparators. A region of interest in the dmPFC was used to generate whole-brain functional connectivity maps pre-treatment and post treatment. Ten of 20 patients met the response criteria (⩾50% improvement on Yale-Brown Obsessive-Compulsive Scale, YBOCS); response to dmPFC-rTMS was sharply bimodal. dmPFC-rTMS responders had higher dmPFC-ventral striatal connectivity at baseline. The degree of reduction in this connectivity, from pre- to post-treatment, correlated to the degree of YBOCS symptomatic improvement. Baseline clinical and psychometric data did not predict treatment response. In summary, reductions in fronto-striatal hyperconnectivity were associated with treatment response to dmPFC-rTMS in OCD. This finding is consistent with previous fMRI studies of deep brain stimulation in OCD, but opposite to previous reports on mechanisms of dmPFC-rTMS in major depression. fMRI could prove useful in predicting the response to dmPFC-rTMS in OCD. PMID:26440813

Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rTMS.

PubMed

Dunlop, Katharine; Woodside, Blake; Olmsted, Marion; Colton, Patricia; Giacobbe, Peter; Downar, Jonathan

2016-04-01

Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of nonresponse to conventional treatments. OCD pathophysiology is believed to involve abnormalities in cortico-striatal-thalamic-cortical circuits through regions such as dorsomedial prefrontal cortex (dmPFC) and ventral striatum. These regions may constitute therapeutic targets for neuromodulation treatments, such as repetitive transcranial magnetic stimulation (rTMS). However, the neurobiological predictors and correlates of successful rTMS treatment for OCD are unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) to identify neural predictors and correlates of response to 20-30 sessions of bilateral 10 Hz dmPFC-rTMS in 20 treatment-resistant OCD patients, with 40 healthy controls as baseline comparators. A region of interest in the dmPFC was used to generate whole-brain functional connectivity maps pre-treatment and post treatment. Ten of 20 patients met the response criteria (⩾50% improvement on Yale-Brown Obsessive-Compulsive Scale, YBOCS); response to dmPFC-rTMS was sharply bimodal. dmPFC-rTMS responders had higher dmPFC-ventral striatal connectivity at baseline. The degree of reduction in this connectivity, from pre- to post-treatment, correlated to the degree of YBOCS symptomatic improvement. Baseline clinical and psychometric data did not predict treatment response. In summary, reductions in fronto-striatal hyperconnectivity were associated with treatment response to dmPFC-rTMS in OCD. This finding is consistent with previous fMRI studies of deep brain stimulation in OCD, but opposite to previous reports on mechanisms of dmPFC-rTMS in major depression. fMRI could prove useful in predicting the response to dmPFC-rTMS in OCD.

Effect of Low-Frequency rTMS and NMES on Subacute Unilateral Hemispheric Stroke With Dysphagia

PubMed Central

Lim, Kil-Byung; Lee, Hong-Jae; Yoo, Jeehyun

2014-01-01

Objective To investigate the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) and neuromuscular electrical stimulation (NMES) on post-stroke dysphagia. Methods Subacute (<3 months), unilateral hemispheric stroke patients with dysphagia were randomly assigned to the conventional dysphagia therapy (CDT), rTMS, or NMES groups. In rTMS group, rTMS was performed at 100% resting motor threshold with 1 Hz frequency for 20 minutes per session (5 days per week for 2 weeks). In NMES group, electrical stimulation was applied to the anterior neck for 30 minutes per session (5 days per week for 2 weeks). All three groups were given conventional dysphagia therapy for 4 weeks. We evaluated the functional dysphagia scale (FDS), pharyngeal transit time (PTT), the penetration-aspiration scale (PAS), and the American Speech-Language Hearing Association National Outcomes Measurement System (ASHA NOMS) swallowing scale at baseline, after 2 weeks, and after 4 weeks. Results Forty-seven patients completed the study; 15 in the CDT group, 14 in the rTMS group, and 18 in the NMES group. Mean changes in FDS and PAS for liquid during first 2 weeks in the rTMS and NMES groups were significantly higher than those in the CDT group, but no significant differences were found between the rTMS and NMES group. No significant difference in mean changes of FDS and PAS for semi-solid, PTT, and ASHA NOMS was observed among the three groups. Conclusion These results indicated that both low-frequency rTMS and NMES could induce early recovery from dysphagia; therefore, they both could be useful therapeutic options for dysphagic stroke patients. PMID:25379488

The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI

PubMed Central

Plow, Ela B.; Cattaneo, Zaira; Carlson, Thomas A.; Alvarez, George A.; Pascual-Leone, Alvaro; Battelli, Lorella

2014-01-01

A balance of mutual tonic inhibition between bi-hemispheric posterior parietal cortices is believed to play an important role in bilateral visual attention. However, experimental support for this notion has been mainly drawn from clinical models of unilateral damage. We have previously shown that low-frequency repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a contralateral attentional deficit in bilateral visual tracking. Here, we used functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily disrupts the inter-hemispheric balance between bilateral IPS in visual attention. Following application of 1 Hz rTMS over the left IPS, subjects performed a bilateral visual tracking task while their brain activity was recorded using fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS. Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL), lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL), Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal areas (MT+), showed higher activity. The brain activity of the homologues of these regions in the un-stimulated, right hemisphere was reversed. Interestingly, the evolution of network-wide activation related to attentional behavior following rTMS showed that activation of most occipital synergists adaptively compensated for contralateral and ipsilateral decrement after rTMS, while activation of parietal synergists, and SoG remained competing. This pattern of ipsilateral and contralateral activations empirically supports the hypothesized loss of inter-hemispheric balance that underlies clinical manifestation of visual attentional extinction. PMID:24860462

Novel TMS coils designed using an inverse boundary element method

NASA Astrophysics Data System (ADS)

Cobos Sánchez, Clemente; María Guerrero Rodriguez, Jose; Quirós Olozábal, Ángel; Blanco-Navarro, David

2017-01-01

In this work, a new method to design TMS coils is presented. It is based on the inclusion of the concept of stream function of a quasi-static electric current into a boundary element method. The proposed TMS coil design approach is a powerful technique to produce stimulators of arbitrary shape, and remarkably versatile as it permits the prototyping of many different performance requirements and constraints. To illustrate the power of this approach, it has been used for the design of TMS coils wound on rectangular flat, spherical and hemispherical surfaces, subjected to different constraints, such as minimum stored magnetic energy or power dissipation. The performances of such coils have been additionally described; and the torque experienced by each stimulator in the presence of a main magnetic static field have theoretically found in order to study the prospect of using them to perform TMS and fMRI concurrently. The obtained results show that described method is an efficient tool for the design of TMS stimulators, which can be applied to a wide range of coil geometries and performance requirements.

Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial.

PubMed

Kozel, F Andrew; Motes, Michael A; Didehbani, Nyaz; DeLaRosa, Bambi; Bass, Christina; Schraufnagel, Caitlin D; Jones, Penelope; Morgan, Cassie Rae; Spence, Jeffrey S; Kraut, Michael A; Hart, John

2018-03-15

The objective was to test whether repetitive Transcranial Magnetic Stimulation (rTMS) just prior to Cognitive Processing Therapy (CPT) would significantly improve the clinical outcome compared to sham rTMS prior to CPT in veterans with PTSD. Veterans 18-60 years of age with current combat-related PTSD symptoms were randomized, using a 1:1 ratio in a parallel design, to active (rTMS+CPT) versus sham (sham+CPT) rTMS just prior to weekly CPT for 12-15 sessions. Blinded raters evaluated veterans at baseline, after the 5th and 9th treatments, and at 1, 3, and 6 months post-treatment. Clinician Administered PTSD Scale (CAPS) was the primary outcome measure with the PTSD Checklist (PCL) as a secondary outcome measure. The TMS coil (active or sham) was positioned over the right dorsolateral prefrontal cortex (110% MT, 1Hz continuously for 30min, 1800 pulses/treatment). Of the 515 individuals screened for the study, 103 participants were randomized to either active (n = 54) or sham rTMS (n = 49). Sixty-two participants (60%) completed treatment and 59 (57%) completed the 6-month assessment. The rTMS+CPT group showed greater symptom reductions from baseline on both CAPS and PCL across CPT sessions and follow-up assessments, t(df ≥ 325) ≤ -2.01, p ≤ 0.023, one-tailed and t(df ≥ 303) ≤ -2.14, p ≤ 0.017, one-tailed, respectively. Participants were predominantly male and limited to one era of conflicts as well as those who could safely undergo rTMS. The addition of rTMS to CPT compared to sham with CPT produced significantly greater PTSD symptom reduction early in treatment and was sustained up to six months post-treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

The analgesic effect of therapeutic rTMS is not mediated or predicted by comorbid psychiatric or sleep disorders

PubMed Central

Lindholm, Pauliina; Lamusuo, Salla; Taiminen, Tero; Virtanen, Arja; Pertovaara, Antti; Forssell, Heli; Hagelberg, Nora; Jääskeläinen, Satu

2016-01-01

Abstract Background: Mechanisms underlying alleviation of neuropathic pain by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) and right secondary somatosensory cortex (S2) are only partly known. Patients with chronic neuropathic pain often have comorbidities like depression and sleep problems. Through functional connectivity, rTMS of M1 and S2 may activate dorsolateral prefrontal cortex, the target for treating depression with rTMS. Thus, the analgesic effect of rTMS could be mediated indirectly via improvement of psychiatric comorbidities or sleep. We examined whether rTMS has an independent analgesic effect or whether its clinical benefits depend on effects on mood or sleep. We also evaluated if comorbid psychiatric or sleep disorders predict the treatment outcome. Methods: Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized controlled crossover rTMS study. Patients’ psychiatric history was evaluated by a specialist in psychiatry. Intensity and interference of pain, mood, and the quality of sleep and life were evaluated at baseline and after 2 active (primary somatosensory cortex [S1]/M1 and S2) and placebo rTMS treatments. A logistic regression analysis was done to investigate predictors of treatment outcome. Results: The analgesic effect of the right S2 stimulation was not associated with improvement of psychiatric conditions or sleep, whereas S1/M1 stimulation improved sleep without significant analgesic effect (P = 0.013–0.046 in sleep scores). Psychiatric and sleep disorders were more common in patients than in the general population (P = 0.000–0.001 in sleep scores), but these comorbidities did not predict the rTMS treatment outcome. Conclusion: We conclude that rTMS to the right S2 does not exert its beneficial analgesic effects in chronic neuropathic orofacial pain via indirect improvement of comorbid psychiatric or sleep disorders. PMID:27858874

Memory-guided saccade processing in visual form agnosia (patient DF).

PubMed

Rossit, Stéphanie; Szymanek, Larissa; Butler, Stephen H; Harvey, Monika

2010-01-01

According to Milner and Goodale's model (The visual brain in action, Oxford University Press, Oxford, 2006) areas in the ventral visual stream mediate visual perception and oV-line actions, whilst regions in the dorsal visual stream mediate the on-line visual control of action. Strong evidence for this model comes from a patient (DF), who suffers from visual form agnosia after bilateral damage to the ventro-lateral occipital region, sparing V1. It has been reported that she is normal in immediate reaching and grasping, yet severely impaired when asked to perform delayed actions. Here we investigated whether this dissociation would extend to saccade execution. Neurophysiological studies and TMS work in humans have shown that the posterior parietal cortex (PPC), on the right in particular (supposedly spared in DF), is involved in the control of memory-guided saccades. Surprisingly though, we found that, just as reported for reaching and grasping, DF's saccadic accuracy was much reduced in the memory compared to the stimulus-guided condition. These data support the idea of a tight coupling of eye and hand movements and further suggest that dorsal stream structures may not be sufficient to drive memory-guided saccadic performance.

Cost-effectiveness of preoperative motor mapping with navigated transcranial magnetic brain stimulation in patients with high-grade glioma.

PubMed

Butenschön, Vicki M; Ille, Sebastian; Sollmann, Nico; Meyer, Bernhard; Krieg, Sandro M

2018-06-01

OBJECTIVE Navigated transcranial magnetic stimulation (nTMS) is used to identify the motor cortex prior to surgery. Yet, there has, until now, been no published evidence on the economic impact of nTMS. This study aims to analyze the cost-effectiveness of nTMS, evaluating the incremental costs of nTMS motor mapping per additional quality-adjusted life year (QALY). By doing so, this study also provides a model allowing for future analysis of general cost-effectiveness of new neuro-oncological treatment options. METHODS The authors used a microsimulation model based on their cohort population sampled for 1000 patients over the time horizon of 2 years. A health care provider perspective was used to assemble direct costs of total treatment. Transition probabilities and health utilities were based on published literature. Effects were stated in QALYs and established for health state subgroups. RESULTS In all scenarios, preoperative mapping was considered cost-effective with a willingness-to-pay threshold < 3*per capita GDP (gross domestic product). The incremental cost-effectiveness ratio (ICER) of nTMS versus no nTMS was 45,086 Euros/QALY. Sensitivity analyses showed robust results with a high impact of total treatment costs and utility of progression-free survival. Comparing the incremental costs caused by nTMS implementation only, the ICER decreased to 1967 Euros/QALY. CONCLUSIONS Motor mapping prior to surgery provides a cost-effective tool to improve the clinical outcome and overall survival of high-grade glioma patients in a resource-limited setting. Moreover, the model used in this study can be used in the future to analyze new treatment options in neuro-oncology in terms of their general cost-effectiveness.

Analysis Of Condensate Samples In Support Of The Antifoam Degradation Study

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

Hay, M.; Martino, C.

2016-01-12

The degradation of Antifoam 747 to form flammable decomposition products has resulted in declaration of a Potential Inadequacy in the Safety Analysis (PISA) for the Defense Waste Processing Facility (DWPF). Savannah River National Laboratory (SRNL) testing with simulants showed that hexamethyldisiloxane (HMDSO), trimethylsilanol (TMS), and 1-propanal are formed in the offgas from the decomposition of the antifoam. A total of ten DWPF condensate samples from Batch 735 and 736 were analyzed by SRNL for three degradation products and additional analytes. All of the samples were analyzed to determine the concentrations of HMDSO, TMS, and propanal. The results of the organicmore » analysis found concentrations for propanal and HMDSO near or below the detection limits for the analysis. The TMS concentrations ranged from below detection to 11 mg/L. The samples from Batch 736 were also analyzed for formate and oxalate anions, total organic carbon, and aluminum, iron, manganese, and silicon. Most of the samples contained low levels of formate and therefore low levels of organic carbon. These two values for each sample show reasonable agreement in most cases. Low levels of all the metals (Al, Fe, Mn, and Si) were present in most of the samples.« less

ANALYSIS OF CONDENSATE SAMPLES IN SUPPORT OF THE ANTIFOAM DEGRADATION STUDY

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

Hay, M.; Martino, C.

2016-02-29

The degradation of Antifoam 747 to form flammable decomposition products has resulted in declaration of a Potential Inadequacy in the Safety Analysis (PISA) for the Defense Waste Processing Facility (DWPF). Savannah River National Laboratory (SRNL) testing with simulants showed that hexamethyldisiloxane (HMDSO), trimethylsilanol (TMS), and 1-propanal are formed in the offgas from the decomposition of the antifoam. A total of ten DWPF condensate samples from Batch 735 and 736 were analyzed by SRNL for three degradation products and additional analytes. All of the samples were analyzed to determine the concentrations of HMDSO, TMS, and propanal. The results of the organicmore » analysis found concentrations for propanal and HMDSO near or below the detection limits for the analysis. The TMS concentrations ranged from below detection to 11 mg/L. The samples from Batch 736 were also analyzed for formate and oxalate anions, total organic carbon, and aluminum, iron, manganese, and silicon. Most of the samples contained low levels of formate and therefore low levels of organic carbon. These two values for each sample show reasonable agreement in most cases. Low levels of all the metals (Al, Fe, Mn, and Si) were present in most of the samples.« less

Thioredoxin is not a marker for treatment-resistance depression but associated with cognitive function: An rTMS study.

PubMed

Aydın, Efruz Pirdoğan; Genç, Abdullah; Dalkıran, Mihriban; Uyar, Ece Türkyilmaz; Deniz, İpek; Özer, Ömer Akil; Karamustafalıoğlu, Kayıhan Oğuz

2018-01-03

Elevated oxidative stress is known to play an important role in development of depression and cognitive dysfunction. To date, thioredoxin (TRX), an antioxidant protein, has been investigated as a marker for psychiatric disorders such as schizophrenia, bipolar disorder and autism but its relationship with depression is yet to be unknown. The aim of this study is to detect the TRX levels in patients with treatment-resistant depression (TRD), analyse the effect of rTMS (repetitive transcranial magnetic stimulation) application on TRX levels and display the relationship of TRX with cognitive areas. This study included 27 treatment-resistant unipolar depression patients and 29 healthy subjects. Patients were evaluated by Hamilton Depression Scale (HDRS), Hamilton Anxiety Scale (HARS) and Montreal Cognitive Assessment (MoCA) before and after rTMS application. 23 of TRD patients were applied high-frequency rTMS over left DLPFC for 2 to 4weeks and plasma TRX levels of patients and healthy subjects were measured. No significant difference was determined between the TRX levels of patients and healthy subjects (p>0.05). After rTMS application there were significant decrease in severity of depression (p<0.001) and anxiety (p<0.001), and explicit improvement in cognitive areas (delayed memory, visual-spatial/executive abilities and language points) (all p<0.05). No difference was detected in TRX levels of the patients after rTMS application (p>0.005). High language scores of the patients were found to be associated with high TRX levels (p<0.005). Our study indicates that TRX levels cannot be used as a marker for TRD or rTMS treatment in TRD. In spite of this TRX levels have a positive correlation with language functions of the patients of TRD. More extensive studies are required to clarify the mechanism of action of TRX and the effect of TRX on cognitive functions. Copyright © 2017 Elsevier Inc. All rights reserved.

Lateralization in motor facilitation during action observation: a TMS study.

PubMed

Aziz-Zadeh, Lisa; Maeda, Fumiko; Zaidel, Eran; Mazziotta, John; Iacoboni, Marco

2002-05-01

Action observation facilitates corticospinal excitability. This is presumably due to a premotor neural system that is active when we perform actions and when we observe actions performed by others. It has been speculated that this neural system is a precursor of neural systems subserving language. If this theory is true, we may expect hemispheric differences in the motor facilitation produced by action observation, with the language-dominant left hemisphere showing stronger facilitation than the right hemisphere. Furthermore, it has been suggested that body parts are recognized via cortical regions controlling sensory and motor processing associated with that body part. If this is true, then corticospinal facilitation during action observation should be modulated by the laterality of the observed body part. The present study addressed these two issues using TMS for each motor cortex separately as participants observed actions being performed by a left hand, a right hand, or a control stimulus on the computer screen. We found no overall difference between the right and left hemisphere for motor-evoked potential (MEP) size during action observation. However, when TMS was applied to the left motor cortex, MEPs were larger while observing right hand actions. Likewise, when TMS was applied to the right motor cortex, MEPs were larger while observing left hand actions. Our data do not suggest left hemisphere superiority in the facilitating effects of action observation on the motor system. However, they do support the notion of a sensory-motor loop according to which sensory stimulus properties (for example, the image of a left hand or a right hand) directly affect motor cortex activity, even when no motor output is required. The pattern of this effect is congruent with the pattern of motor representation in each hemisphere.

Predictors of response to repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder.

PubMed

Beuzon, G; Timour, Q; Saoud, M

2017-02-01

Repetitive transcranial magnetic stimulation (rTMS), based on the principle of electromagnetic induction, consists of applying series of magnetic impulses to the cerebral cortex so as to modulate neurone activity in a target zone. This technique, still experimental, could prove promising in the field of psychiatry, in particular for the treatment of major depressive disorder. It is important for the clinician to be able to assess the response potential of a given patient to rTMS, and this among other things requires relevant predictive factors to be available. This review of the literature aims to determine and analyse reported predictive factors for therapeutic response to rTMS treatment in major depressive disorder. Different parameters are studied, in particular age, the severity of the depressive episode, psychological dimensions, genetic factors, cerebral blood flows via cerebral imagery, and neuronavigation. The factors found to be associated with better therapeutic response were young age, low level of severity of the depressive episode, motor threshold intensity over 100%, more than 1000 stimulations per session, more than 10 days treatment, L/L genotype on the 5-HTTLPR transporter gene, C/C homozygosity on the promotor regions of the 5-HT1A receptor gene, Val/Val homozygosity on the BDNF gene, cordance analyses by EEG, and finally the accurate localisation provided by neuronavigation. The authors conclude that investigations in larger patient samples are required in the future, and that the work already achieved should provide lines of approach for the coming experimental studies. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Abnormal motor cortex excitability during linguistic tasks in adductor-type spasmodic dysphonia.

PubMed

Suppa, A; Marsili, L; Giovannelli, F; Di Stasio, F; Rocchi, L; Upadhyay, N; Ruoppolo, G; Cincotta, M; Berardelli, A

2015-08-01

In healthy subjects (HS), transcranial magnetic stimulation (TMS) applied during 'linguistic' tasks discloses excitability changes in the dominant hemisphere primary motor cortex (M1). We investigated 'linguistic' task-related cortical excitability modulation in patients with adductor-type spasmodic dysphonia (ASD), a speech-related focal dystonia. We studied 10 ASD patients and 10 HS. Speech examination included voice cepstral analysis. We investigated the dominant/non-dominant M1 excitability at baseline, during 'linguistic' (reading aloud/silent reading/producing simple phonation) and 'non-linguistic' tasks (looking at non-letter strings/producing oral movements). Motor evoked potentials (MEPs) were recorded from the contralateral hand muscles. We measured the cortical silent period (CSP) length and tested MEPs in HS and patients performing the 'linguistic' tasks with different voice intensities. We also examined MEPs in HS and ASD during hand-related 'action-verb' observation. Patients were studied under and not-under botulinum neurotoxin-type A (BoNT-A). In HS, TMS over the dominant M1 elicited larger MEPs during 'reading aloud' than during the other 'linguistic'/'non-linguistic' tasks. Conversely, in ASD, TMS over the dominant M1 elicited increased-amplitude MEPs during 'reading aloud' and 'syllabic phonation' tasks. CSP length was shorter in ASD than in HS and remained unchanged in both groups performing 'linguistic'/'non-linguistic' tasks. In HS and ASD, 'linguistic' task-related excitability changes were present regardless of the different voice intensities. During hand-related 'action-verb' observation, MEPs decreased in HS, whereas in ASD they increased. In ASD, BoNT-A improved speech, as demonstrated by cepstral analysis and restored the TMS abnormalities. ASD reflects dominant hemisphere excitability changes related to 'linguistic' tasks; BoNT-A returns these excitability changes to normal. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

NASA Astrophysics Data System (ADS)

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

2009-04-01

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

Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes.

PubMed

Senço, Natasha M; Huang, Yu; D'Urso, Giordano; Parra, Lucas C; Bikson, Marom; Mantovani, Antonio; Shavitt, Roseli G; Hoexter, Marcelo Q; Miguel, Eurípedes C; Brunoni, André R

2015-07-01

Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. Although DBS, rTMS and tDCS are not directly comparable and our theoretical model, based on DBS and rTMS targets, needs empirical validation, we found that the tDCS montage with the cathode over the pre-supplementary motor area and extra-cephalic anode seems to activate most of the areas related to OCD.

Comparing the effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy in the treatment of depression: a systematic review and meta-analysis.

PubMed

Micallef-Trigona, Beppe

2014-01-01

Electroconvulsive therapy (ECT) is the longest standing psychiatric treatment available and has unequivocal benefit in severe depression. However this treatment comes with a number of side effects such as memory impairment. On the other hand, Repetitive Transcranial Magnetic Stimulation (rTMS) is a relatively new form of treatment which has been shown to be efficacious in patients suffering from a number of psychopathologies, including severe depression, with few reported side effects. Due to its potential therapeutic efficacy and lack of side effects, rTMS has gained traction in the treatment of depression, with a number of authors keen to see it take over from ECT. However, it is not clear whether rTMS represents a therapeutic alternative to ECT. This meta-analysis will therefore compare the "gold standard" treatment for severe depression, with the relatively new but promising rTMS. A literature search will be performed with the intention to include all randomised clinical trials. The null hypothesis is that there is no difference in the antidepressant efficacy between the two types of treatment modalities. Statistical analysis of Hamilton Depression Rating Scale (HDRS) scores will be performed.

Effect of Transcranial Magnetic Stimulation on Neuronal Networks

NASA Astrophysics Data System (ADS)

Unsal, Ahmet; Hadimani, Ravi; Jiles, David

2013-03-01

The human brain contains around 100 billion nerve cells controlling our day to day activities. Consequently, brain disorders often result in impairments such as paralysis, loss of coordination and seizure. It has been said that 1 in 5 Americans suffer some diagnosable mental disorder. There is an urgent need to understand the disorders, prevent them and if possible, develop permanent cure for them. As a result, a significant amount of research activities is being directed towards brain research. Transcranial Magnetic Stimulation (TMS) is a promising tool for diagnosing and treating brain disorders. It is a non-invasive treatment method that produces a current flow in the brain which excites the neurons. Even though TMS has been verified to have advantageous effects on various brain related disorders, there have not been enough studies on the impact of TMS on cells. In this study, we are investigating the electrophysiological effects of TMS on one dimensional neuronal culture grown in a circular pathway. Electrical currents are produced on the neuronal networks depending on the directionality of the applied field. This aids in understanding how neuronal networks react under TMS treatment.

Trunk Motion System (TMS) Using Printed Body Worn Sensor (BWS) via Data Fusion Approach

PubMed Central

Mokhlespour Esfahani, Mohammad Iman; Zobeiri, Omid; Moshiri, Behzad; Narimani, Roya; Mehravar, Mohammad; Rashedi, Ehsan; Parnianpour, Mohamad

2017-01-01

Human movement analysis is an important part of biomechanics and rehabilitation, for which many measurement systems are introduced. Among these, wearable devices have substantial biomedical applications, primarily since they can be implemented both in indoor and outdoor applications. In this study, a Trunk Motion System (TMS) using printed Body-Worn Sensors (BWS) is designed and developed. TMS can measure three-dimensional (3D) trunk motions, is lightweight, and is a portable and non-invasive system. After the recognition of sensor locations, twelve BWSs were printed on stretchable clothing with the purpose of measuring the 3D trunk movements. To integrate BWSs data, a neural network data fusion algorithm was used. The outcome of this algorithm along with the actual 3D anatomical movements (obtained by Qualisys system) were used to calibrate the TMS. Three healthy participants with different physical characteristics participated in the calibration tests. Seven different tasks (each repeated three times) were performed, involving five planar, and two multiplanar movements. Results showed that the accuracy of TMS system was less than 1.0°, 0.8°, 0.6°, 0.8°, 0.9°, and 1.3° for flexion/extension, left/right lateral bending, left/right axial rotation, and multi-planar motions, respectively. In addition, the accuracy of TMS for the identified movement was less than 2.7°. TMS, developed to monitor and measure the trunk orientations, can have diverse applications in clinical, biomechanical, and ergonomic studies to prevent musculoskeletal injuries, and to determine the impact of interventions. PMID:28075342

Electrophysiological correlates of stimulus-driven reorienting deficits after interference with right parietal cortex during a spatial attention task: a TMS-EEG study

PubMed Central

Capotosto, Paolo; Corbetta, Maurizio; Romani, Gian Luca; Babiloni, Claudio

2013-01-01

Transcranial magnetic stimulation (TMS) interference over right intraparietal sulcus (IPS) causally disrupts behaviorally and electroencephalographic (EEG) rhythmic correlates of endogenous spatial orienting prior to visual target presentation (Capotosto et al. 2009; 2011). Here we combine data from our previous studies to examine whether right parietal TMS during spatial orienting also impairs stimulus-driven re-orienting or the ability to efficiently process unattended stimuli, i.e. stimuli outside the current focus of attention. Healthy subjects (N=24) performed a Posner spatial cueing task while their EEG activity was being monitored. Repetitive TMS (rTMS) was applied for 150 milliseconds (ms) simultaneously to the presentation of a central arrow directing spatial attention to the location of an upcoming visual target. Right IPS-rTMS impaired target detection, especially for stimuli presented at unattended locations; it also caused a modulation of the amplitude of parieto-occipital positive ERPs peaking at about 480 ms (P3) post-target. The P3 significantly decreased for unattended targets, and significantly increased for attended targets after right IPS-rTMS as compared to Sham stimulation. Similar effects were obtained for left IPS stimulation albeit in a smaller group of subjects. We conclude that disruption of anticipatory processes in right IPS has prolonged effects that persist during target processing. The P3 decrement may reflect interference with post-decision processes that are part of stimulus-driven re-orienting. Right IPS is a node of functional interaction between endogenous spatial orienting and stimulus-driven re-orienting processes in human vision. PMID:22905824

Electromagnetic Fields for the Regulation of Neural Stem Cells

PubMed Central

Cui, Mengchu; Ge, Hongfei; Zhao, Hengli; Zou, Yongjie

2017-01-01

Localized magnetic fields (MFs) could easily penetrate the scalp, skull, and meninges, thus inducing an electrical current in both the central and peripheral nervous systems, which is primarily used in transcranial magnetic stimulation (TMS) for inducing specific effects on different regions or cells that play roles in various brain activities. Studies of repetitive transcranial magnetic stimulation (rTMS) have led to novel attractive therapeutic approaches. Neural stem cells (NSCs) in adult human brain are able to self-renew and possess multidifferential ability to maintain homeostasis and repair damage after acute central nervous system. In the present review, we summarized the electrical activity of NSCs and the fundamental mechanism of electromagnetic fields and their effects on regulating NSC proliferation, differentiation, migration, and maturation. Although it was authorized for the rTMS use in resistant depression patients by US FDA, there are still unveiling mechanism and limitations for rTMS in clinical applications of acute central nervous system injury, especially on NSC regulation as a rehabilitation strategy. More in-depth studies should be performed to provide detailed parameters and mechanisms of rTMS in further studies, making it a powerful tool to treat people who are surviving with acute central nervous system injuries. PMID:28932245

Therapeutic administration of atomoxetine combined with rTMS and occupational therapy for upper limb hemiparesis after stroke: a case series study of three patients.

PubMed

Kinoshita, Shoji; Kakuda, Wataru; Yamada, Naoki; Momosaki, Ryo; Okuma, Ryo; Watanabe, Shu; Abo, Masahiro

2016-03-01

Atomoxetine, a selective noradrenaline reuptake inhibitor, has been reported to enhance brain plasticity, but has not yet been used in stroke patients. We reported the feasibility and clinical benefits on motor functional recovery of the combination of repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) in stroke patients. This pilot study was designed to evaluate the additive effects of oral atomoxetine to rTMS/OT in post-stroke hemiparetic patients. The study included three post-stroke patients with upper limb hemiparesis. Treatment with 40 mg/day atomoxetine commenced 2 weeks before admission. After confirming tolerance, the dose was increased to 120 mg/day. Low-frequency rTMS/OT was provided daily for 15 days during continued atomoxetine therapy. Motor function of the affected upper limb was evaluated with the Fugl-Meyer Assessment and Wolf Motor Function test. All patients completed the protocol and showed motor improvement up to 4 weeks after the treatment. No atomoxetine-related side effects were noted. Our protocol of triple therapy of atomoxetine, low-frequency rTMS, and OT is safe and feasible intervention for upper limb hemiparesis after stroke.

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

PubMed Central

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 ASD based on behavioral and cognitive testing. PMID:27007257

Non-invasive brain stimulation to investigate language production in healthy speakers: A meta-analysis.

PubMed

Klaus, Jana; Schutter, Dennis J L G

2018-06-01

Non-invasive brain stimulation (NIBS) has become a common method to study the interrelations between the brain and language functioning. This meta-analysis examined the efficacy of transcranial magnetic stimulation (TMS) and direct current stimulation (tDCS) in the study of language production in healthy volunteers. Forty-five effect sizes from 30 studies which investigated the effects of NIBS on picture naming or verbal fluency in healthy participants were meta-analysed. Further sub-analyses investigated potential influences of stimulation type, control, target site, task, online vs. offline application, and current density of the target electrode. Random effects modelling showed a small, but reliable effect of NIBS on language production. Subsequent analyses indicated larger weighted mean effect sizes for TMS as compared to tDCS studies. No statistical differences for the other sub-analyses were observed. We conclude that NIBS is a useful method for neuroscientific studies on language production in healthy volunteers. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Delayed recovery of the affected finger extensors at chronic stage in a stroke patient: A case report.

PubMed

Jang, Sung Ho; Lee, Han Do

2017-10-01

A 33-year-old male presented with complete weakness of the right extremities due to corona radiata infarct. The main concerns of the patient is recovery of hand function especially related to finger extension. Right corona radiata infarct. He underwent physical therapy and occupational therapy at the outpatient clinic of the rehabilitation department of the same university hospital until 2 years after onset. In addition, he underwent neuromuscular electrical stimulation for the right finger extensors continuously until 4 years after onset. At 6 months after onset, the weakness of his right side recovered to subnormal state except for the right finger extensors which were completely weak. At 1.5 years after onset, the right finger extensors began to show slow and continuous recovery. At 4 years after onset, the patient showed motor recovery in the right finger extensors to the extent that he was able to move against gravity. Discontinuation of the left corticospinal tract was observed on 2-month diffusion tensor tractography (DTT); however, the integrity of this discontinuation had recovered to the primary motor cortex on 4-year DTT. On 2-month transcranial magnetic stimulation (TMS), no motor-evoked potential was evoked; in contrast, motor-evoked potentials were obtained at the right-hand muscle on 4-year TMS study. We demonstrated unusual delayed and long-term recovery of the affected finger extensors in a patient with corona radiata infarct using DTT and TMS.

Correlating subcortical interhemispheric connectivity and cortical hemispheric dominance in brain tumor patients: A repetitive navigated transcranial magnetic stimulation study.

PubMed

Sollmann, Nico; Ille, Sebastian; Tussis, Lorena; Maurer, Stefanie; Hauck, Theresa; Negwer, Chiara; Bauer, Jan S; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

2016-02-01

The present study aims to investigate the relationship between transcallosal interhemispheric connectivity (IC) and hemispheric language lateralization by using a novel approach including repetitive navigated transcranial magnetic stimulation (rTMS), hemispheric dominance ratio (HDR) calculation, and rTMS-based diffusion tensor imaging fiber tracking (DTI FT). 31 patients with left-sided perisylvian brain lesions underwent diffusion tensor imaging (DTI) and rTMS language mapping. Cortical language-positive rTMS spots were used to calculate HDRs (HDR: quotient of the left-sided divided by right-sided naming error rates for corresponding left- and right-sided cortical regions) and to create regions of interest (ROIs) for DTI FT. Then, fibers connecting the rTMS-based ROIs of both hemispheres were tracked, and the correlation of IC to HDRs was calculated via Spearman's rank correlation coefficient (rs). Fibers connecting rTMS-based ROIs of both hemispheres were detected in 12 patients (38.7%). Within the patients in which IC was detected, the mean number of subcortical IC fibers ± standard deviation (SD) was 138.0 ± 346.5 (median: 7.5; range: 1-1,217 fibers). Regarding rs for the correlation of HDRs and fiber numbers of patients that showed IC, only moderate correlation was revealed. Our approach might be beneficial and technically feasible for further investigation of the relationship between IC and language lateralization. However, only moderate correlation was revealed in the present study. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of TMS1 Silencing in the Resistance of Breast Cancer Cells to Apoptosis

DTIC Science & Technology

2006-08-01

USA 93: Kelliher MA, Grimm S, Ishida Y, Kuo F , Stanger BZ, Leder 14486-14491. P. (1998). Immunity 8: 297-303. Stehlik C , Fiorentino L , Dorfleutner A ...Caspase-8 - TMS1.. -. - GAPDH - . B. CuX+ siRNA: CHX TRAIL Lamin A / C + - + - TMS1 + - + Procaspase-8 f t Cleaved Caspase-8 - - 3 TMS1 . 03-tubulin...analysis for caspase-8, TMS 1 and either GAPDH or P3-tubulin as indicated. siRNA: Lamin A / C TMS1 TNFa+CHX - +- - + TRAIL -+ - + PARP -m l PARP p85

A Single Session of rTMS Enhances Small-Worldness in Writer's Cramp: Evidence from Simultaneous EEG-fMRI Multi-Modal Brain Graph.

PubMed

Bharath, Rose D; Panda, Rajanikant; Reddam, Venkateswara Reddy; Bhaskar, M V; Gohel, Suril; Bhardwaj, Sujas; Prajapati, Arvind; Pal, Pramod Kumar

2017-01-01

Background and Purpose : Repetitive transcranial magnetic stimulation (rTMS) induces widespread changes in brain connectivity. As the network topology differences induced by a single session of rTMS are less known we undertook this study to ascertain whether the network alterations had a small-world morphology using multi-modal graph theory analysis of simultaneous EEG-fMRI. Method : Simultaneous EEG-fMRI was acquired in duplicate before (R1) and after (R2) a single session of rTMS in 14 patients with Writer's Cramp (WC). Whole brain neuronal and hemodynamic network connectivity were explored using the graph theory measures and clustering coefficient, path length and small-world index were calculated for EEG and resting state fMRI (rsfMRI). Multi-modal graph theory analysis was used to evaluate the correlation of EEG and fMRI clustering coefficients. Result : A single session of rTMS was found to increase the clustering coefficient and small-worldness significantly in both EEG and fMRI ( p < 0.05). Multi-modal graph theory analysis revealed significant modulations in the fronto-parietal regions immediately after rTMS. The rsfMRI revealed additional modulations in several deep brain regions including cerebellum, insula and medial frontal lobe. Conclusion : Multi-modal graph theory analysis of simultaneous EEG-fMRI can supplement motor physiology methods in understanding the neurobiology of rTMS in vivo . Coinciding evidence from EEG and rsfMRI reports small-world morphology for the acute phase network hyper-connectivity indicating changes ensuing low-frequency rTMS is probably not "noise".

Transcranial magnetic stimulation for treating depression in elderly patients

PubMed Central

Sayar, Gokben Hizli; Ozten, Eylem; Tan, Oguz; Tarhan, Nevzat

2013-01-01

Purpose The aim of the study reported here was to examine the safety and effectiveness of high-frequency repetitive transcranial magnetic stimulation (rTMS) in elderly patients with depression. Patients and methods Sixty-five depressed elderly patients received rTMS over their left prefrontal cortex for 6 days per week, from Monday to Saturday, for 3 weeks. The rTMS intensity was set at 100% of the motor threshold and 25 Hz stimulation with a duration of 2 seconds and was delivered 20 times at 30-second intervals. A full course comprised an average of 1000 magnetic pulses. Depression was rated using the Hamilton Depression Rating Scale (HAMD) before and after treatment. Response was defined as a 50% reduction in HAMD score. Patients with HAMD scores < 8 were considered to be in remission. Results The mean HAMD score for the study group decreased from 21.94 ± 5.12 before treatment to 11.28 ± 4.56 after rTMS (P < 0.001). Following the treatment period, 58.46% of the study group demonstrated significant mood improvement, as indexed by a reduction of more than 50% on the HAMD score. Nineteen of these 38 patients attained remission (HAMD score < 8), while 41.54% of all study patients achieved a partial response. None of the patients had a worsened HAMD score at the end of the treatment. Treatment was generally well tolerated and no serious adverse effects were reported. Conclusion In this study, rTMS was found to be a safe, well-tolerated treatment, and a useful adjunctive treatment to medications in elderly treatment-resistant depressed patients. This study contributes to the existing evidence on the antidepressant effect of rTMS in the treatment of depression in patients over 60 years of age. PMID:23723700

High‐Performance Lithium‐Oxygen Battery Electrolyte Derived from Optimum Combination of Solvent and Lithium Salt

PubMed Central

Ahn, Su Mi; Suk, Jungdon; Kim, Do Youb; Kim, Hwan Kyu

2017-01-01

Abstract To fabricate a sustainable lithium‐oxygen (Li‐O2) battery, it is crucial to identify an optimum electrolyte. Herein, it is found that tetramethylene sulfone (TMS) and lithium nitrate (LiNO3) form the optimum electrolyte, which greatly reduces the overpotential at charge, exhibits superior oxygen efficiency, and allows stable cycling for 100 cycles. Linear sweep voltammetry (LSV) and differential electrochemical mass spectrometry (DEMS) analyses reveal that neat TMS is stable to oxidative decomposition and exhibit good compatibility with a lithium metal. But, when TMS is combined with typical lithium salts, its performance is far from satisfactory. However, the TMS electrolyte containing LiNO3 exhibits a very low overpotential, which minimizes the side reactions and shows high oxygen efficiency. LSV‐DEMS study confirms that the TMS‐LiNO3 electrolyte efficiently produces NO2 −, which initiates a redox shuttle reaction. Interestingly, this NO2 −/NO2 redox reaction derived from the LiNO3 salt is not very effective in solvents other than TMS. Compared with other common Li‐O2 solvents, TMS seems optimum solvent for the efficient use of LiNO3 salt. Good compatibility with lithium metal, high dielectric constant, and low donicity of TMS are considered to be highly favorable to an efficient NO2 −/NO2 redox reaction, which results in a high‐performance Li‐O2 battery. PMID:29051863

Use of the Temperament and Character Inventory to Predict Response to Repetitive Transcranial Magnetic Stimulation for Major Depression

PubMed Central

Siddiqi, Shan H.; Chockalingam, Ravikumar; Cloninger, C. Robert; Lenze, Eric J.; Cristancho, Pilar

2016-01-01

Objective . The goal of this study was to investigate the utility of the Temperament and Character Inventory (TCI) in predicting antidepressant response to repetitive transcranial magnetic stimulation (rTMS). Background Although rTMS of the dorsolateral prefrontal cortex (DLPFC) is an established antidepressant treatment, little is known about predictors of response. The TCI measures multiple personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, self-transcendence, and cooperativeness), some of which have predicted response to pharmacotherapy and cognitive-behavioral therapy. A previous study suggested a possible association between self-directedness and response to rTMS in melancholic depression, although this was limited by the fact that melancholic depression is associated with a limited range of TCI profiles. Methods . Nineteen patients with a major depressive episode completed the TCI prior to a clinical course of rTMS over the DLPFC. Treatment response was defined as ≥50% decrease in scores on the Hamilton Rating Scale for Depression (HAM-D). Baseline scores on each TCI dimension were compared between responders and non-responders via analysis of variance. Pearson correlations were also calculated for temperament/character scores in comparison with percentage improvement in HAM-D scores. Results Eleven of the 19 patients responded to rTMS. T-scores for persistence were significantly higher in responders than in non-responders (P=0.022). Linear regression revealed a correlation between persistence scores and percentage improvement in HAM-D scores. Conclusions Higher persistence scores predicted antidepressant response to rTMS. This may be explained by rTMS-induced enhancement of cortical excitability, which has been found to be decreased in patients with high persistence. Personality assessment that includes measurement of TCI persistence may be a useful component of precision medicine initiatives in rTMS for depression. PMID:27123799

Transcranial magnetic stimulation and transcranial direct current stimulation: treatments for cognitive and neuropsychiatric symptoms in the neurodegenerative dementias?

PubMed Central

2014-01-01

Introduction Two methods of non-invasive brain stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have demonstrable positive effects on cognition and can ameliorate neuropsychiatric symptoms such as depression. Less is known about the efficacy of these approaches in common neurodegenerative diseases. In this review, we evaluate the effects of TMS and tDCS upon cognitive and neuropsychiatric symptoms in the major dementias, including Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson’s disease with dementia (PDD), and frontotemporal dementia (FTD), as well as the potential pre-dementia states of Mild Cognitive Impairment (MCI) and Parkinson’s disease (PD). Methods PubMed (until 7 February 2014) and PsycINFO (from 1967 to January Week 3 2014) databases were searched in a semi-systematic manner in order to identify relevant treatment studies. A total of 762 studies were identified and 32 studies (18 in the dementias and 14 in PD populations) were included. Results No studies were identified in patients with PDD, FTD or VaD. Of the dementias, 13 studies were conducted in patients with AD, one in DLB, and four in MCI. A total of 16 of the 18 studies showed improvements in at least one cognitive or neuropsychiatric outcome measure. Cognitive or neuropsychiatric improvements were observed in 12 of the 14 studies conducted in patients with PD. Conclusions Both TMS and tDCS may have potential as interventions for the treatment of symptoms associated with dementia and PD. These results are promising; however, available data were limited, particularly within VaD, PDD and FTD, and major challenges exist in order to maximise the efficacy and clinical utility of both techniques. In particular, stimulation parameters vary considerably between studies and are likely to subsequently impact upon treatment efficacy. PMID:25478032

The Treatment Motivation Scales for forensic outpatient treatment (TMS-F): construction and psychometric evaluation.

PubMed

Drieschner, Klaus H; Boomsma, Anne

2008-06-01

The Treatment Motivation Scales for forensic outpatient treatment (TMS-F) is a Dutch 85-item self-report questionnaire for the motivation of forensic outpatients to engage in their treatment and six cognitive and affective determinants of this motivation. Following descriptions of the conceptual basis and construction, the psychometric properties of the TMS-F are evaluated in two studies. In Study 1 (N = 378), the factorial structure of the instrument and the dimensionality of its scales are evaluated by confirmative factor analysis. In Study 2 with a new sample (N = 376), the results of Study 1 are largely confirmed. It is found that the factorial structure of the TMS-F is in accordance with expectations, that all scales are sufficiently homogeneous and reliable to interpret the sum scores, and that these results are stable across independent samples. The relative importance of the six determinants of the motivation to engage in the treatment and the generalizability of the results are discussed.

The observation of manual grasp actions affects the control of speech: a combined behavioral and Transcranial Magnetic Stimulation study.

PubMed

Gentilucci, Maurizio; Campione, Giovanna Cristina; Dalla Volta, Riccardo; Bernardis, Paolo

2009-12-01

Does the mirror system affect the control of speech? This issue was addressed in behavioral and Transcranial Magnetic Stimulation (TMS) experiments. In behavioral experiment 1, participants pronounced the syllable /da/ while observing (1) a hand grasping large and small objects with power and precision grasps, respectively, (2) a foot interacting with large and small objects and (3) differently sized objects presented alone. Voice formant 1 was higher when observing power as compared to precision grasp, whereas it remained unaffected by observation of the different types of foot interaction and objects alone. In TMS experiment 2, we stimulated hand motor cortex, while participants observed the two types of grasp. Motor Evoked Potentials (MEPs) of hand muscles active during the two types of grasp were greater when observing power than precision grasp. In experiments 3-5, TMS was applied to tongue motor cortex of participants silently pronouncing the syllable /da/ and simultaneously observing power and precision grasps, pantomimes of the two types of grasps, and differently sized objects presented alone. Tongue MEPs were greater when observing power than precision grasp either executed or pantomimed. Finally, in TMS experiment 6, the observation of foot interaction with large and small objects did not modulate tongue MEPs. We hypothesized that grasp observation activated motor commands to the mouth as well as to the hand that were congruent with the hand kinematics implemented in the observed type of grasp. The commands to the mouth selectively affected postures of phonation organs and consequently basic features of phonological units.

Lasting EEG/MEG Aftereffects of Rhythmic Transcranial Brain Stimulation: Level of Control Over Oscillatory Network Activity

PubMed Central

Veniero, Domenica; Vossen, Alexandra; Gross, Joachim; Thut, Gregor

2015-01-01

A number of rhythmic protocols have emerged for non-invasive brain stimulation (NIBS) in humans, including transcranial alternating current stimulation (tACS), oscillatory transcranial direct current stimulation (otDCS), and repetitive (also called rhythmic) transcranial magnetic stimulation (rTMS). With these techniques, it is possible to match the frequency of the externally applied electromagnetic fields to the intrinsic frequency of oscillatory neural population activity (“frequency-tuning”). Mounting evidence suggests that by this means tACS, otDCS, and rTMS can entrain brain oscillations and promote associated functions in a frequency-specific manner, in particular during (i.e., online to) stimulation. Here, we focus instead on the changes in oscillatory brain activity that persist after the end of stimulation. Understanding such aftereffects in healthy participants is an important step for developing these techniques into potentially useful clinical tools for the treatment of specific patient groups. Reviewing the electrophysiological evidence in healthy participants, we find aftereffects on brain oscillations to be a common outcome following tACS/otDCS and rTMS. However, we did not find a consistent, predictable pattern of aftereffects across studies, which is in contrast to the relative homogeneity of reported online effects. This indicates that aftereffects are partially dissociated from online, frequency-specific (entrainment) effects during tACS/otDCS and rTMS. We outline possible accounts and future directions for a better understanding of the link between online entrainment and offline aftereffects, which will be key for developing more targeted interventions into oscillatory brain activity. PMID:26696834

Effect of low-frequency rTMS on aphasia in stroke patients: a meta-analysis of randomized controlled trials.

PubMed

Ren, Cai-Li; Zhang, Guo-Fu; Xia, Nan; Jin, Chun-Hui; Zhang, Xiu-Hua; Hao, Jian-Feng; Guan, Hong-Bo; Tang, Hong; Li, Jian-An; Cai, De-Liang

2014-01-01

Small clinical trials have reported that low-frequency repetitive transcranial magnetic stimulation (rTMS) might improve language recovery in patients with aphasia after stroke. However, no systematic reviews or meta-analyses studies have investigated the effect of rTMS on aphasia. The objective of this study was to perform a meta-analysis of studies that explored the effects of low-frequency rTMS on aphasia in stroke patients. We searched PubMed, CENTRAL, Embase, CINAHL, ScienceDirect, and Journals@Ovid for randomized controlled trials published between January 1965 and October 2013 using the keywords "aphasia OR language disorders OR anomia OR linguistic disorders AND repetitive transcranial magnetic stimulation OR rTMS". We used fixed- and random-effects models to estimate the standardized mean difference (SMD) and a 95% CI for the language outcomes. Seven eligible studies involving 160 stroke patients were identified in this meta-analysis. A significant effect size of 1.26 was found for the language outcome severity of impairment (95% CI = 0.80 to 1.71) without heterogeneity (I2 = 0%, P = 0.44). Further analyses demonstrated prominent effects for the naming subtest (SMD = 0.52, 95% CI = 0.18 to 0.87), repetition (SMD = 0.54, 95% CI = 0.16 to 0.92), writing (SMD = 0.70, 95% CI = 0.19 to 1.22), and comprehension (the Token test: SMD = 0.58, 95% CI = 0.07 to 1.09) without heterogeneity (I2 = 0%). The SMD of AAT and BDAE comprehension subtests was 0.32 (95% CI = -0.08 to 0.72) with moderate heterogeneity (I2 = 32%,P = 0.22). The effect size did not change significantly even when any one trial was eliminated. None of the patients from the 7 included articles reported adverse effects from rTMS. Low-frequency rTMS with a 90% resting motor threshold that targets the triangular part of the right inferior frontal gyrus (IFG) has a positive effect on language recovery in patients with aphasia following stroke. Further well-designed studies with larger populations are required to ascertain the long-term effects of rTMS in aphasia treatment.

Effects of Bilateral Repetitive Transcranial Magnetic Stimulation on Post-Stroke Dysphagia.

PubMed

Park, Eunhee; Kim, Min Su; Chang, Won Hyuk; Oh, Su Mi; Kim, Yun Kwan; Lee, Ahee; Kim, Yun-Hee

Optimal protocol of repetitive transcranial magnetic stimulation (rTMS) on post-stroke dysphagia remains uncertain with regard to its clinical efficacy. The aim of the present study is to investigate the effects of high-frequency rTMS at the bilateral motor cortices over the cortical representation of the mylohyoid muscles in the patients with post-stroke dysphagia. This study was a single-blind, randomized controlled study with a blinded observer. Thirty-five stroke patients were randomly divided into three intervention groups: the bilateral stimulation group, the unilateral stimulation group, and the sham stimulation group. For the bilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional and 500 pulses of 10 Hz rTMS over the contralesional motor cortices over the cortical areas that project to the mylohyoid muscles were administered daily for 2 consecutive weeks. For the unilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional motor cortex over the cortical representation of the mylohyoid muscle and the same amount of sham rTMS over the contralesional hemisphere were applied. For the sham stimulation group, sham rTMS was applied at the bilateral motor cortices. Clinical swallowing function and videofluoroscopic swallowing studies were assessed before the intervention (T0), immediately after the intervention (T1) and 3 weeks after the intervention (T2) using Clinical Dysphagia Scale (CDS), Dysphagia Outcome and Severity Scale (DOSS), Penetration Aspiration Scale (PAS), and Videofluoroscopic Dysphagia Scale (VDS). There were significant time and intervention interaction effects in the CDS, DOSS, PAS, and VDS scores (p < 0.05). In the direct comparison of the changes in the swallowing parameters among the three groups, the change in CDS scores at T1 and T2 showed a significantly higher improvement in the bilateral simulation group than in two other groups (p < 0.05). There was a significantly larger change in the DOSS, PAS, and VDS scores at T1 in the bilateral stimulation group than in two other groups (p < 0.05). The results of the present study provide substantial evidence that 10 Hz rTMS at the bilateral motor cortices over the cortical areas projecting to the mylohyoid muscles is effective as an additional treatment strategy to traditional dysphagia therapies. Copyright © 2016. Published by Elsevier Inc.

Role of the motor system in language knowledge.

PubMed

Berent, Iris; Brem, Anna-Katharine; Zhao, Xu; Seligson, Erica; Pan, Hong; Epstein, Jane; Stern, Emily; Galaburda, Albert M; Pascual-Leone, Alvaro

2015-02-17

All spoken languages express words by sound patterns, and certain patterns (e.g., blog) are systematically preferred to others (e.g., lbog). What principles account for such preferences: does the language system encode abstract rules banning syllables like lbog, or does their dislike reflect the increased motor demands associated with speech production? More generally, we ask whether linguistic knowledge is fully embodied or whether some linguistic principles could potentially be abstract. To address this question, here we gauge the sensitivity of English speakers to the putative universal syllable hierarchy (e.g., blif ≻ bnif ≻ bdif ≻ lbif) while undergoing transcranial magnetic stimulation (TMS) over the cortical motor representation of the left orbicularis oris muscle. If syllable preferences reflect motor simulation, then worse-formed syllables (e.g., lbif) should (i) elicit more errors; (ii) engage more strongly motor brain areas; and (iii) elicit stronger effects of TMS on these motor regions. In line with the motor account, we found that repetitive TMS pulses impaired participants' global sensitivity to the number of syllables, and functional MRI confirmed that the cortical stimulation site was sensitive to the syllable hierarchy. Contrary to the motor account, however, ill-formed syllables were least likely to engage the lip sensorimotor area and they were least impaired by TMS. Results suggest that speech perception automatically triggers motor action, but this effect is not causally linked to the computation of linguistic structure. We conclude that the language and motor systems are intimately linked, yet distinct. Language is designed to optimize motor action, but its knowledge includes principles that are disembodied and potentially abstract.

Role of the motor system in language knowledge

PubMed Central

Berent, Iris; Brem, Anna-Katharine; Zhao, Xu; Seligson, Erica; Pan, Hong; Epstein, Jane; Stern, Emily; Galaburda, Albert M.; Pascual-Leone, Alvaro

2015-01-01

All spoken languages express words by sound patterns, and certain patterns (e.g., blog) are systematically preferred to others (e.g., lbog). What principles account for such preferences: does the language system encode abstract rules banning syllables like lbog, or does their dislike reflect the increased motor demands associated with speech production? More generally, we ask whether linguistic knowledge is fully embodied or whether some linguistic principles could potentially be abstract. To address this question, here we gauge the sensitivity of English speakers to the putative universal syllable hierarchy (e.g., blif≻bnif≻bdif≻lbif) while undergoing transcranial magnetic stimulation (TMS) over the cortical motor representation of the left orbicularis oris muscle. If syllable preferences reflect motor simulation, then worse-formed syllables (e.g., lbif) should (i) elicit more errors; (ii) engage more strongly motor brain areas; and (iii) elicit stronger effects of TMS on these motor regions. In line with the motor account, we found that repetitive TMS pulses impaired participants’ global sensitivity to the number of syllables, and functional MRI confirmed that the cortical stimulation site was sensitive to the syllable hierarchy. Contrary to the motor account, however, ill-formed syllables were least likely to engage the lip sensorimotor area and they were least impaired by TMS. Results suggest that speech perception automatically triggers motor action, but this effect is not causally linked to the computation of linguistic structure. We conclude that the language and motor systems are intimately linked, yet distinct. Language is designed to optimize motor action, but its knowledge includes principles that are disembodied and potentially abstract. PMID:25646465

Poststroke dysphagia rehabilitation by repetitive transcranial magnetic stimulation: a noncontrolled pilot study.

PubMed

Verin, E; Leroi, A M

2009-06-01

Poststroke dysphagia is frequent and significantly increases patient mortality. In two thirds of cases there is a spontaneous improvement in a few weeks, but in the other third, oropharyngeal dysphagia persists. Repetitive transcranial magnetic stimulation (rTMS) is known to excite or inhibit cortical neurons, depending on stimulation frequency. The aim of this noncontrolled pilot study was to assess the feasibility and the effects of 1-Hz rTMS, known to have an inhibitory effect, on poststroke dysphagia. Seven patients (3 females, age = 65 +/- 10 years), with poststroke dysphagia due to hemispheric or subhemispheric stroke more than 6 months earlier (56 +/- 50 months) diagnosed by videofluoroscopy, participated in the study. rTMS at 1 Hz was applied for 20 min per day every day for 5 days to the healthy hemisphere to decrease transcallosal inhibition. The evaluation was performed using the dysphagia handicap index and videofluoroscopy. The dysphagia handicap index demonstrated that the patients had mild oropharyngeal dysphagia. Initially, the score was 43 +/- 9 of a possible 120 which decreased to 30 +/- 7 (p < 0.05) after rTMS. After rTMS, there was an improvement of swallowing coordination, with a decrease in swallow reaction time for liquids (p = 0.0506) and paste (p < 0.01), although oral transit time, pharyngeal transit time, and laryngeal closure duration were not modified. Aspiration score significantly decreased for liquids (p < 0.05) and residue score decreased for paste (p < 0.05). This pilot study demonstrated that rTMS is feasible in poststroke dysphagia and improves swallowing coordination. Our results now need to be confirmed by a randomized controlled study with a larger patient population.

Enhancing picture naming with transcranial magnetic stimulation.

PubMed

Mottaghy, Felix M; Sparing, Roland; Töpper, Rudolf

2006-01-01

The enhancement of cognitive function in healthy subjects by medication, training or intervention yields increasing political, social and ethical attention. In this paper facilitatory effects of single-pulse TMS and repetitive TMS on a simple picture naming task are presented. A significant shortening of picture naming latencies was observed after single-pulse TMS over Wernicke's area. The accuracy of the response was not affected by this speed effect. After TMS over the dominant motor cortex or over the non-dominant temporal lobe, however, no facilitation of picture naming was observed. In the rTMS experiments only rTMS of Wernicke's area had an impact on picture naming latencies resulting in a shortening of naming latencies without affecting the accuracy of the response. rTMS over the visual cortex, Broca's area or over the corresponding sites in the non-dominant hemisphere had no effect. Single-pulse TMS is able to facilitate lexical processes due to a general preactivation of language-related neuronal networks when delivered over Wernicke's area. Repetitive transcranial magnetic stimulation over Wernicke's area also leads to a brief facilitation of picture naming possibly by shortening linguistic processing time. Whether TMS or rTMS can be used to aid linguistic therapy in the rehabilitation phase of aphasic patients should be subject of further investigations.

rTMS for PTSD: induced merciful oblivion or elimination of abnormal hypermnesia?

PubMed

Rossi, Simone; Cappa, Stefano F; Ulivelli, Monica; De Capua, Alberto; Bartalini, Sabina; Rossini, Paolo M

2006-01-01

Neuroimaging studies and experimental data suggest that symptoms of posttraumatic stress disorder (PTSD) are associated with dysfunctions of neural circuits linking prefrontal cortex and the limbic system that have a role in autobiographic episodic memory. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been suggested to be beneficial to patients with PTSD, transiently alleviating re-experiencing as well as avoidance reactions and associated anxiety symptoms. In healthy humans, converging evidence suggests that rTMS of the right DLPFC interferes with episodic memory retrieval. Hence, we hypothesize that daily applications of rTMS in PTSD patients may reduce access to the set of autobiographical stored events, that, if re-experienced, may cause the overt PTSD symptoms.

PET-Based Confirmation of Orientation Sensitivity of TMS-Induced Cortical Activation in Humans

PubMed Central

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2017-01-01

Background Currently, it is difficult to predict precise regions of cortical activation in response to transcranial magnetic stimulation (TMS). Most analytical approaches focus on applied magnetic field strength in the target region as the primary factor, placing activation on the gyral crowns. However, imaging studies support M1 targets being typically located in the sulcal banks. Objective/hypothesis To more thoroughly investigate this inconsistency, we sought to determine whether neocortical surface orientation was a critical determinant of regional activation. Methods MR images were used to construct cortical and scalp surfaces for 18 subjects. The angle (θ) between the cortical surface normal and its nearest scalp normal for ~50,000 cortical points per subject was used to quantify cortical location (i.e., gyral vs. sulcal). TMS-induced activations of primary motor cortex (M1) were compared to brain activations recorded during a finger-tapping task using concurrent positron emission tomographic (PET) imaging. Results Brain activations were primarily sulcal for both the TMS and task activations (P < 0.001 for both) compared to the overall cortical surface orientation. Also, the location of maximal blood flow in response to either TMS or finger-tapping correlated well using the cortical surface orientation angle or distance to scalp (P < 0.001 for both) as criteria for comparison between different neocortical activation modalities. Conclusion This study provides further evidence that a major factor in cortical activation using TMS is the orientation of the cortical surface with respect to the induced electric field. The results show that, despite the gyral crown of the cortex being subjected to a larger magnetic field magnitude, the sulcal bank of M1 had larger cerebral blood flow (CBF) responses during TMS. PMID:23827648

rTMS of the occipital cortex abolishes Braille reading and repetition priming in blind subjects.

PubMed

Kupers, R; Pappens, M; de Noordhout, A Maertens; Schoenen, J; Ptito, M; Fumal, A

2007-02-27

To study the functional involvement of the visual cortex in Braille reading, we applied repetitive transcranial magnetic stimulation (rTMS) over midoccipital (MOC) and primary somatosensory (SI) cortex in blind subjects. After rTMS of MOC, but not SI, subjects made significantly more errors and showed an abolishment of the improvement in reading speed following repetitive presentation of the same word list, suggesting a role of the visual cortex in repetition priming in the blind.

Repetitive transcranial magnetic stimulation for generalised anxiety disorder: a pilot randomised, double-blind, sham-controlled trial.

PubMed

Diefenbach, Gretchen J; Bragdon, Laura B; Zertuche, Luis; Hyatt, Christopher J; Hallion, Lauren S; Tolin, David F; Goethe, John W; Assaf, Michal

2016-09-01

Repetitive transcranial magnetic stimulation (rTMS) holds promise for treating generalised anxiety disorder (GAD) but has only been studied in uncontrolled research. This is the first randomised controlled trial (clinicaltrials.gov: NCT01659736) to investigate the efficacy and neural correlates of rTMS in GAD. Twenty five participants (active n = 13; sham, n = 12) enrolled. rTMS was targeted at the right dorsolateral prefrontal cortex (DLPFC, 1 Hz, 90% resting motor threshold). Response and remission rates were higher in the active v. sham groups and there were significant group × time interactions for anxiety, worry and depressive symptoms, favouring active v. sham. In addition, right DLPFC activation during a decision-making gambling task increased at post-treatment for active rTMS only, and changes in neuroactivation correlated significantly with changes in worry symptoms. Findings provide preliminary evidence that rTMS may improve GAD symptoms in association with modifying neural activity in the stimulation site. © The Royal College of Psychiatrists 2016.

The role of the prefrontal cortex in controlling gender-stereotypical associations: a TMS investigation.

PubMed

Cattaneo, Zaira; Mattavelli, Giulia; Platania, Elisa; Papagno, Costanza

2011-06-01

Stereotypes associated with gender, race, ethnicity and religion are powerful forces in human social interactions. Previous neuroimaging and neuropsychological studies point to a role of the prefrontal cortex in controlling stereotypical responses. Here we used transcranial magnetic stimulation (TMS) in combination with an Implicit Association Test (IAT) to highlight the possible causal role of the left dorsolateral prefrontal cortex (DLPFC) and the right anterior dorsomedial prefrontal cortex (aDMPFC) in controlling gender-stereotypical responses. Young male and female participants were tested. Our results showed that applying TMS over the left DLPFC and the right aDMPFC increased the gender-stereotypical bias in male participants compared to when TMS was applied to a control site (vertex). This suggests that both the left DLPFC and the right aDMPFC play a direct role in stereotyping. Females did not show a significant gender bias on the IAT; correspondingly their responses were unaffected by TMS. Copyright © 2011 Elsevier Inc. All rights reserved.

TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia

PubMed Central

Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro

2011-01-01

This study sought to discover if an optimum 1 cm2 area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions. PMID:21864891

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Sehatzadeh, Shayan; Tu, Hong Anh; Palimaka, Stefan; Yap, Belinda; O'Reilly, Daria; Bowen, Jim; Higgins, Caroline; Holubowich, Corinne

2016-01-01

Background To date, several randomized controlled trials (RCTs) have shown the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression. Objective This analysis examined the antidepressant efficacy of rTMS in patients with treatment-resistant unipolar depression. Methods A literature search was performed for RCTs published from January 1, 1994, to November 20, 2014. The search was updated on March 1, 2015. Two independent reviewers evaluated the abstracts for inclusion, reviewed full texts of eligible studies, and abstracted data. Meta-analyses were conducted to obtain summary estimates. The primary outcome was changes in depression scores measured by the Hamilton Rating Scale for Depression (HRSD), and we considered, a priori, the mean difference of 3.5 points to be a clinically important treatment effect. Remission and response to the treatment were secondary outcomes, and we calculated number needed to treat on the basis of these outcomes. We examined the possibility of publication bias by constructing funnel plots and by Begg's and Egger's tests. A meta-regression was undertaken to examine the effect of specific rTMS technical parameters on the treatment effects. Results Twenty-three RCTs compared rTMS with sham, and six RCTs compared rTMS with electroconvulsive therapy (ECT). Trials of rTMS versus sham showed a statistically significant improvement in depression scores with rTMS (weighted mean difference [WMD] 2.31, 95% CI 1.19–3.43; P < .001). This improvement was smaller than the pre-specified clinically important treatment effect. There was a 10% absolute difference between rTMS and sham in the rates of remission or response. This translates to a number needed to treat of 10. Risk ratios for remission and response were 2.20 (95% CI 1.44–3.38, P = .001 and 1.72 [95% CI], 1.13–2.62, P = .01), respectively, favouring rTMS. No publication bias was detected. Trials of rTMS versus ECT showed a statistically and clinically significant difference between rTMS and ECT in favour of ECT (WMD 5.97, 95% CI 0.94–11.0, P = .02). Risk ratios for remission and response were 1.44 (95% CI 0.64–3.23, P = .38) and 1.72 (95% CI 0.95–3.11, P = .07), respectively, favouring ECT. Conclusions Overall, the body of evidence favoured ECT for treatment of patients who are treatment-resistant. Repetitive transcranial magnetic stimulation had a small short-term effect for improving depression in comparison with sham, but follow-up studies did not show that the small effect will continue for longer periods. PMID:27099642

Is Life better after motor cortex stimulation for pain control? Results at long-term and their prediction by preoperative rTMS.

PubMed

André-Obadia, Nathalie; Mertens, Patrick; Lelekov-Boissard, Taïssia; Afif, Afif; Magnin, Michel; Garcia-Larrea, Luis

2014-01-01

A positive effect of motor cortex stimulation (MCS) (defined as subjective estimations of pain relief ≥ 30%) has been reported in 55 - 64% of patients. Repetitive magnetic cortical stimulation (rTMS) is considered a predictor of MCS effect. These figures are, however, mostly based on subjective reports of pain intensity, and have not been confirmed in the long-term. This study assessed long-term pain relief (2 - 9 years) after epidural motor cortex stimulation and its pre-operative prediction by rTMS, using both intensity and Quality of Life (QoL) scales. Analysis of the long-term evolution of pain patients treated by epidural motor cortex stimulation, and predictive value of preoperative response to rTMS. University Neurological Hospital Pain Center. Twenty patients suffering chronic pharmaco-resistant neuropathic pain. All patients received first randomized sham vs. active 20 Hz-rTMS, before being submitted to MCS surgery. Postoperative pain relief was evaluated at 6 months and then up to 9 years post-MCS (average 6.1 ± 2.6 y) using (i) pain numerical rating scores (NRS); (ii) a combined assessment (CPA) including NRS, drug intake, and subjective quality of life; and (iii) a short questionnaire (HowRu) exploring discomfort, distress, disability, and dependence. Pain scores were significantly reduced by active (but not sham) rTMS and by subsequent MCS. Ten out of 20 patients kept a long-term benefit from MCS, both on raw pain scores and on CPA. The CPA results were strictly comparable when obtained by the surgeon or by a third-party on telephonic survey (r = 0.9). CPA scores following rTMS and long-term MCS were significantly associated (Fisher P = 0.02), with 90% positive predictive value and 67% negative predictive value of preoperative rTMS over long-term MCS results. On the HowRu questionnaire, long-term MCS-related improvement concerned "discomfort" (physical pain) and "dependence" (autonomy for daily activities), whereas "disability" (work, home, and leisure activities) and "distress" (anxiety, stress, depression) did not significantly improve. Limited cohort of patients with inhomogeneous pain etiology. Subjectivity of the reported items by the patient after a variable and long delay after surgery. Predictive evaluation based on a single rTMS session compared to chronic MCS. Half of the patients still retain a significant benefit after 2 - 9 years of continuous MCS, and this can be reasonably predicted by preoperative rTMS. Adding drug intake and QoL estimates to raw pain scores allows a more realistic assessment of long-term benefits and enhance the rTMS predictive value. The aims of this study and its design were approved by the local ethics committee (University Hospitals St Etienne and Lyon, France).

Effect of low-frequency rTMS on electromagnetic tomography (LORETA) and regional brain metabolism (PET) in schizophrenia patients with auditory hallucinations.

PubMed

Horacek, Jiri; Brunovsky, Martin; Novak, Tomas; Skrdlantova, Lucie; Klirova, Monika; Bubenikova-Valesova, Vera; Krajca, Vladimir; Tislerova, Barbora; Kopecek, Milan; Spaniel, Filip; Mohr, Pavel; Höschl, Cyril

2007-01-01

Auditory hallucinations are characteristic symptoms of schizophrenia with high clinical importance. It was repeatedly reported that low frequency (

The Impact of Accelerated Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Cue-Reactivity: An fMRI Study on Craving in Recently Detoxified Alcohol-Dependent Patients

PubMed Central

Herremans, Sarah C.; Van Schuerbeek, Peter; De Raedt, Rudi; Matthys, Frieda; Buyl, Ronald; De Mey, Johan; Baeken, Chris

2015-01-01

In alcohol-dependent patients craving is a difficult-to-treat phenomenon. It has been suggested that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may have beneficial effects. However, exactly how this application exerts its effect on the underlying craving neurocircuit is currently unclear. In an effort to induce alcohol craving and to maximize detection of HF-rTMS effects to cue-induced alcohol craving, patients were exposed to a block and event-related alcohol cue-reactivity paradigm while being scanned with fMRI. Hence, we assessed the effect of right dorsolateral prefrontal cortex (DLPFC) stimulation on cue-induced and general alcohol craving, and the related craving neurocircuit. Twenty-six recently detoxified alcohol-dependent patients were included. First, we evaluated the impact of one sham-controlled stimulation session. Second, we examined the effect of accelerated right DLPFC HF-rTMS treatment: here patients received 15 sessions in an open label accelerated design, spread over 4 consecutive days. General craving significantly decreased after 15 active HF-rTMS sessions. However, cue-induced alcohol craving was not altered. Our brain imaging results did not show that the cue-exposure affected the underlying craving neurocircuit after both one and fifteen active HF-rTMS sessions. Yet, brain activation changes after one and 15 HF-rTMS sessions, respectively, were observed in regions associated with the extended reward system and the default mode network, but only during the presentation of the event-related paradigm. Our findings indicate that accelerated HF-rTMS applied to the right DLPFC does not manifestly affect the craving neurocircuit during an alcohol-related cue-exposure, but instead it may influence the attentional network. PMID:26295336

Contribution of the pre-SMA to the production of words and non-speech oral motor gestures, as revealed by repetitive transcranial magnetic stimulation (rTMS).

PubMed

Tremblay, Pascale; Gracco, Vincent L

2009-05-01

An emerging theoretical perspective, largely based on neuroimaging studies, suggests that the pre-SMA is involved in planning cognitive aspects of motor behavior and language, such as linguistic and non-linguistic response selection. Neuroimaging studies, however, cannot indicate whether a brain region is equally important to all tasks in which it is activated. In the present study, we tested the hypothesis that the pre-SMA is an important component of response selection, using an interference technique. High frequency repetitive TMS (10 Hz) was used to interfere with the functioning of the pre-SMA during tasks requiring selection of words and oral gestures under different selection modes (forced, volitional) and attention levels (high attention, low attention). Results show that TMS applied to the pre-SMA interferes selectively with the volitional selection condition, resulting in longer RTs. The low- and high-attention forced selection conditions were unaffected by TMS, demonstrating that the pre-SMA is sensitive to selection mode but not attentional demands. TMS similarly affected the volitional selection of words and oral gestures, reflecting the response-independent nature of the pre-SMA contribution to response selection. The implications of these results are discussed.

The Neurobiological Grounding of Persistent Stuttering: from Structure to Function.

PubMed

Neef, Nicole E; Anwander, Alfred; Friederici, Angela D

2015-09-01

Neuroimaging and transcranial magnetic stimulation provide insights into the neuronal mechanisms underlying speech disfluencies in chronic persistent stuttering. In the present paper, the goal is not to provide an exhaustive review of existing literature, but rather to highlight robust findings. We, therefore, conducted a meta-analysis of diffusion tensor imaging studies which have recently implicated disrupted white matter connectivity in stuttering. A reduction of fractional anisotropy in persistent stuttering has been reported at several different loci. Our meta-analysis revealed consistent deficits in the left dorsal stream and in the interhemispheric connections between the sensorimotor cortices. In addition, recent fMRI meta-analyses link stuttering to reduced left fronto-parieto-temporal activation while greater fluency is associated with boosted co-activations of right fronto-parieto-temporal areas. However, the physiological foundation of these irregularities is not accessible with MRI. Complementary, transcranial magnetic stimulation (TMS) reveals local excitatory and inhibitory regulation of cortical dynamics. Applied to a speech motor area, TMS revealed reduced speech-planning-related neuronal dynamics at the level of the primary motor cortex in stuttering. Together, this review provides a focused view of the neurobiology of stuttering to date and may guide the rational design of future research. This future needs to account for the perpetual dynamic interactions between auditory, somatosensory, and speech motor circuits that shape fluent speech.

Evolution of the oligopeptide transporter family.

PubMed

Gomolplitinant, Kenny M; Saier, Milton H

2011-03-01

The oligopeptide transporter (OPT) family of peptide and iron-siderophore transporters includes members from both prokaryotes and eukaryotes but with restricted distribution in the latter domain. Eukaryotic members were found only in fungi and plants with a single slime mold homologue clustering with the fungal proteins. All functionally characterized eukaryotic peptide transporters segregate from the known iron-siderophore transporters on a phylogenetic tree. Prokaryotic members are widespread, deriving from many different phyla. Although they belong only to the iron-siderophore subdivision, genome context analyses suggest that many of them are peptide transporters. OPT family proteins have 16 or occasionally 17 transmembrane-spanning α-helical segments (TMSs). We provide statistical evidence that the 16-TMS topology arose via three sequential duplication events followed by a gene-fusion event for proteins with a seventeenth TMS. The proposed pathway is as follows: 2 TMSs → 4 TMSs → 8 TMSs → 16 TMSs → 17 TMSs. The seventeenth C-terminal TMS, which probably arose just once, is found in just one phylogenetic group of these homologues. Analyses for orthology revealed that a few phylogenetic clusters consist exclusively of orthologues but most have undergone intermixing, suggestive of horizontal transfer. It appears that in this family horizontal gene transfer was frequent among prokaryotes, rare among eukaryotes and largely absent between prokaryotes and eukaryotes as well as between plants and fungi. These observations provide guides for future structural and functional analyses of OPT family members.

Impact of one HF-rTMS session on fine motor function in right-handed healthy female subjects: a comparison of stimulation over the left versus the right dorsolateral prefrontal cortex.

PubMed

Baeken, C; Schrijvers, D L; Sabbe, B G C; Vanderhasselt, M A; De Raedt, R

2012-01-01

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool to investigate neural conduction in motor processes. Most rTMS research has been conducted by targeting the primary motor cortex. Several studies have also found increased psychomotor speed after rTMS of the dorsolateral prefrontal cortex (DLPFC). However, these studies were mainly performed in psychiatric patients, only targeting the left DLPFC, and often without sham control. Moreover, psychomotor speed is mostly measured based on tasks that also require higher executive functions. Here, we examined the lateralized effect of one sham-controlled high-frequency rTMS session applied to the left or right DLPFC on fine motor function in 36 healthy right-handed females, using the Fitts' paradigm. We found a significant improvement in psychomotor speed only after actively stimulating the right DLPFC. Our results support the assumption of a right prefrontal neural network implicated in visuomotor behavior and performance processes, and that the improvement in psychomotor speed is not a secondary effect of decreased mood. Copyright © 2012 S. Karger AG, Basel.

Understanding and enhancing motor recovery after stroke using transcranial magnetic stimulation

PubMed Central

Hoyer, Erik H.; Celnik, Pablo A.

2013-01-01

Stroke is the leading cause of long-term disability. Understanding how people recover from stroke and other brain lesions remain one of the biggest conundrums in neuroscience. As a result, concerted efforts in recent years have focused on investigating the neurophysiological changes that occur in the brain after stroke, and in developing novel strategies to enhance motor recovery. In particular, transcranial magnetic stimulation (TMS) is a non-invasive tool that has been used to investigate the brain plasticity changes resulting from stroke and as a therapeutic modality to safely improve motor function. In this review, we discuss the contributions of TMS to understand how different motor areas, such as the ipsilesional hemisphere, secondary motor areas, and contralesional hemisphere are involved in motor recovery. We also consider recent studies using repetitive TMS (rTMS) in stroke patients to enhance upper extremity function. Although further studies are needed, these investigations provide an important starting point to understand the stimulation parameters and patient characteristics that may influence the optimal response to non-invasive brain stimulation. Future directions of rTMS are discussed in the context of post-stroke motor recovery. PMID:22124033

Non-invasive mapping of calculation function by repetitive navigated transcranial magnetic stimulation.

PubMed

Maurer, Stefanie; Tanigawa, Noriko; Sollmann, Nico; Hauck, Theresa; Ille, Sebastian; Boeckh-Behrens, Tobias; Meyer, Bernhard; Krieg, Sandro M

2016-11-01

Concerning calculation function, studies have already reported on localizing computational function in patients and volunteers by functional magnetic resonance imaging and transcranial magnetic stimulation. However, the development of accurate repetitive navigated TMS (rTMS) with a considerably higher spatial resolution opens a new field in cognitive neuroscience. This study was therefore designed to evaluate the feasibility of rTMS for locating cortical calculation function in healthy volunteers, and to establish this technique for future scientific applications as well as preoperative mapping in brain tumor patients. Twenty healthy subjects underwent rTMS calculation mapping using 5 Hz/10 pulses. Fifty-two previously determined cortical spots of the whole hemispheres were stimulated on both sides. The subjects were instructed to perform the calculation task composed of 80 simple arithmetic operations while rTMS pulses were applied. The highest error rate (80 %) for all errors of all subjects was observed in the right ventral precentral gyrus. Concerning division task, a 45 % error rate was achieved in the left middle frontal gyrus. The subtraction task showed its highest error rate (40 %) in the right angular gyrus (anG). In the addition task a 35 % error rate was observed in the left anterior superior temporal gyrus. Lastly, the multiplication task induced a maximum error rate of 30 % in the left anG. rTMS seems feasible as a way to locate cortical calculation function. Besides language function, the cortical localizations are well in accordance with the current literature for other modalities or lesion studies.

The role of prefrontal and parietal cortices in esthetic appreciation of representational and abstract art: a TMS study.

PubMed

Cattaneo, Zaira; Lega, Carlotta; Gardelli, Chiara; Merabet, Lotfi B; Cela-Conde, Camilo J; Nadal, Marcos

2014-10-01

To explain the biological foundations of art appreciation is to explain one of our species' distinctive traits. Previous neuroimaging and electrophysiological studies have pointed to the prefrontal and the parietal cortex as two critical regions mediating esthetic appreciation of visual art. In this study, we applied transcranial magnetic stimulation (TMS) over the left prefrontal cortex and the right posterior parietal cortex while participants were evaluating whether they liked, and by how much, a particular painting. By depolarizing cell membranes in the targeted regions, TMS transiently interferes with the activity of specific cortical areas, which allows clarifying their role in a given task. Our results show that both regions play a fundamental role in mediating esthetic appreciation. Critically though, the effects of TMS varied depending on the type of art considered (i.e. representational vs. abstract) and on participants' a-priori inclination toward one or the other. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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.

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

PubMed Central

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. PMID:27065812

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

PubMed

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.